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Xue J, Liu J, Zhu R, Ma J, Wang H, Jia Q. Development of ratiometric fluorescent probe based on copper nanoclusters and rhodamine B for the detection of 3-nitrotyrosine. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 336:126035. [PMID: 40090110 DOI: 10.1016/j.saa.2025.126035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 02/23/2025] [Accepted: 03/10/2025] [Indexed: 03/18/2025]
Abstract
3-nitrotyrosine (3-NT) serves as a definitive biomarker of oxidative stress and assumes an essential role in the pathogenesis of diseases, so its detection is crucial for the diagnosis of diseases. Herein, we constructed a dual-emission ratiometric fluorescence probe with copper nanoclusters (CuNCs) and rhodamine B (RhB) as the response and reference signals. In the presence of 3-NT, the fluorescence intensity of CuNCs was significantly quenched through static quenching effect (SQE) and inner filter effect (IFE), whereas the fluorescence intensity of RhB kept unchanged. Notably, the sensor achieves high stability, sensitivity, and selectivity for 3-NT detection. Moreover, a portable sensing platform integrated with a 3D printer and a smartphone was constructed to fulfill the need for convenient measurement. The sensor was subsequently employed to determine 3-NT in both human serum and urine specimens, yielding results that were deemed satisfactory. The probe holds broad application potential and provides some ideas for the fluorescence detection of other biomarkers.
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Affiliation(s)
- Jiangshan Xue
- Department of Laboratory, China-Japan Union Hospital of Jilin University, Changchun 130033, China
| | - Jiaqi Liu
- Department of Laboratory, China-Japan Union Hospital of Jilin University, Changchun 130033, China
| | - Ran Zhu
- College of Chemistry, Jilin University, Changchun 130012, China
| | - Jiutong Ma
- College of Chemistry, Jilin University, Changchun 130012, China
| | - Hai Wang
- Department of Laboratory, China-Japan Union Hospital of Jilin University, Changchun 130033, China
| | - Qiong Jia
- College of Chemistry, Jilin University, Changchun 130012, China.
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Zhong L, Yang J, Syed JN, Zhang Y, Tian Y, Fu X. Alpha-Glucosidase Inhibitors in Aging and Aging-Related Diseases: Clinical Applications and Relevant Mechanisms. Aging Dis 2025:AD.2024.1477. [PMID: 39751859 DOI: 10.14336/ad.2024.1477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 12/19/2024] [Indexed: 01/04/2025] Open
Abstract
Aging is a complex and universal process marked by gradual functional declines at the cellular and tissue levels, often leading to a range of aging-related diseases such as diabetes, cardiovascular diseases, and cancer. Delaying the aging process can help prevent, slow down, and alleviate the severity of these various conditions, enhancing overall health and well-being. Alpha-glucosidase inhibitors (AGIs) are a class of widely used antidiabetic drugs that inhibit alpha-glucosidase in the small intestinal mucosa, delaying carbohydrate absorption and reducing postprandial hyperglycemia. Beyond their roles in diabetes treatment, AGIs have shown potential in extending lifespan and effectively treating aging-related diseases by modulating oxidative stress, gut microbiota, inflammatory responses, and nutrient-sensing pathways. This review summarizes recent advancements in the application of AGIs for preventing and treating aging and aging-related diseases, with a focus on their mechanisms and roles in these processes.
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Affiliation(s)
- Ling Zhong
- Department of Endocrinology and Metabolism, Department of Biotherapy, Laboratory of Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jielin Yang
- Department of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5S 1A1, Canada
| | - Jibran Nehal Syed
- Department of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5S 1A1, Canada
| | - Yuwei Zhang
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yan Tian
- Department of Endocrinology and Metabolism, Department of Biotherapy, Laboratory of Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xianghui Fu
- Department of Endocrinology and Metabolism, Department of Biotherapy, Laboratory of Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
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Bonanni LJ, Wittkopp S, Long C, Aleman JO, Newman JD. A review of air pollution as a driver of cardiovascular disease risk across the diabetes spectrum. Front Endocrinol (Lausanne) 2024; 15:1321323. [PMID: 38665261 PMCID: PMC11043478 DOI: 10.3389/fendo.2024.1321323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
The prevalence of diabetes is estimated to reach almost 630 million cases worldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM2.5) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes. Air pollution exposure is a driver of cardiovascular disease onset and exacerbation and can increase cardiovascular risk among those with diabetes. In this review, we summarize the literature describing the relationships between air pollution exposure, diabetes and cardiovascular disease, highlighting how airborne pollutants can disrupt glucose homeostasis. We discuss how air pollution and diabetes, via shared mechanisms leading to endothelial dysfunction, drive increased cardiovascular disease risk. We identify portable air cleaners as potentially useful tools to prevent adverse cardiovascular outcomes due to air pollution exposure across the diabetes spectrum, while emphasizing the need for further study in this particular population. Given the enormity of the health and financial impacts of air pollution exposure on patients with diabetes, a greater understanding of the interventions to reduce cardiovascular risk in this population is needed.
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Affiliation(s)
- Luke J. Bonanni
- Grossman School of Medicine, New York University (NYU) Langone Health, New York, NY, United States
| | - Sharine Wittkopp
- Division of Cardiovascular Disease, Grossman School of Medicine, New York University (NYU) Langone Health, New York, NY, United States
| | - Clarine Long
- Grossman School of Medicine, New York University (NYU) Langone Health, New York, NY, United States
| | - José O. Aleman
- Division of Endocrinology, Grossman School of Medicine, New York University (NYU) Langone Health, New York, NY, United States
| | - Jonathan D. Newman
- Division of Cardiovascular Disease, Grossman School of Medicine, New York University (NYU) Langone Health, New York, NY, United States
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Fysekidis M, Cosson E, Sabouret P, Takbou K, Sutton A, Charnaux N, Banu I, Testa A, Biondi-Zoccai G, Vicaut E, Valensi P. Insulin analogs as an add-on to metformin after failure to oral treatment in type 2 diabetic patients increase diastole duration. The INSUlin Regimens and VASCular Functions (INSUVASC) study. Minerva Cardiol Angiol 2023; 71:659-672. [PMID: 37405711 DOI: 10.23736/s2724-5683.23.06139-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2023]
Abstract
BACKGROUND Fast acting insulin analogues are known to improve arterial stiffness. The combination of metformin with insulin represents a widely used therapeutic strategy in diabetes. We hypothesized that insulin treatment in patients with type 2 diabetes (T2D) with long-acting, fast-acting or basal bolus insulin as an add-on to metformin would provide additional improvement of arterial stiffness. METHODS The INSUlin Regimens and VASCular Functions (INSUVASC) study is a pilot, randomized, open label three-arms study that included 42 patients with type 2 diabetes (T2D) in primary prevention, after a failure to oral antidiabetic agents. Arterial stiffness measurements were performed at fasting and after a standardized breakfast. During the first visit (V1) pre-randomization, participants took only metformin to perform the tests. The same tests were repeated after 4 weeks of insulin treatment during the second visit (V2). RESULTS Data were available for final analysis in 40 patients, with a mean age of 53.6±9.7 years and a mean duration of diabetes of 10.6±5.6 years. Twenty-one were females (52.5%), hypertension and dyslipidemia were present in 18 (45%) and 17 patients (42.5%), respectively. After insulin treatment, the metabolic control was associated to a decrease in oxidative stress and improvement of endothelial functions, with a post prandial diastole duration increased and a decrease of the peripheral arterial stiffness, with a better post prandial pulse pressure ratio and ejection duration after insulin. In hypertensive patients, insulin treatment provided positive effects by decreasing the pulse wave velocity and improving reflection time. CONCLUSIONS A short time treatment by insulin in addition to metformin improved myocardial perfusion. Moreover, insulin treatment in hypertensive patients provides a better hemodynamic profile in large arteries.
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Affiliation(s)
- Marinos Fysekidis
- Department of Endocrinology, Jean Verdier Hospital, Assistence Publique - Hôpitaux de Paris, Paris13 University, Sorbonne Paris Cité, Paris, France -
- Department of Diabetology-Nutrition, Research Center for Human Nutrition of Ile-de-France, Integrated Obesity Center of North Ile-de-France (CINFO), Bondy, France -
- Center of Research in Epidemiology and Statistics (UMR U1153), National Institute of Health and Medical Research (Inserm), Université Paris13, Sorbonne Paris Cité, Bobigny, France -
| | - Emmanuel Cosson
- Department of Endocrinology, Jean Verdier Hospital, Assistence Publique - Hôpitaux de Paris, Paris13 University, Sorbonne Paris Cité, Paris, France
- Department of Diabetology-Nutrition, Research Center for Human Nutrition of Ile-de-France, Integrated Obesity Center of North Ile-de-France (CINFO), Bondy, France
- Center of Research in Epidemiology and Statistics (UMR U1153), National Institute of Health and Medical Research (Inserm), Université Paris13, Sorbonne Paris Cité, Bobigny, France
| | - Pierre Sabouret
- Heart Institute, Pitié-Salpétrière Hospital, Sorbonne University, Paris, France
- National College of French Cardiologists, Paris, France
| | - Karim Takbou
- Department of Endocrinology, Jean Verdier Hospital, Assistence Publique - Hôpitaux de Paris, Paris13 University, Sorbonne Paris Cité, Paris, France
| | - Angela Sutton
- Biochemistry Department, Jean Verdier Hospital, Assistence Publique - Hôpitaux de Paris, Bondy, France
| | - Nathalie Charnaux
- Biochemistry Department, Jean Verdier Hospital, Assistence Publique - Hôpitaux de Paris, Bondy, France
| | - Isabela Banu
- Department of Endocrinology, Jean Verdier Hospital, Assistence Publique - Hôpitaux de Paris, Paris13 University, Sorbonne Paris Cité, Paris, France
| | - Alberto Testa
- Sapienza School for Advanced Studies, Sapienza University, Rome, Italy
| | - Giuseppe Biondi-Zoccai
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy
- Mediterranea Cardiocentro, Naples, Italy
| | - Eric Vicaut
- Clinical Research Unit, Lariboisière-St Louis, Fernand Widal Hospitals, Assistence Publique - Hôpitaux de Paris, Paris, France
| | - Paul Valensi
- Department of Endocrinology, Jean Verdier Hospital, Assistence Publique - Hôpitaux de Paris, Paris13 University, Sorbonne Paris Cité, Paris, France
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Curieses Andrés CM, Pérez de la Lastra JM, Andrés Juan C, Plou FJ, Pérez-Lebeña E. From reactive species to disease development: Effect of oxidants and antioxidants on the cellular biomarkers. J Biochem Mol Toxicol 2023; 37:e23455. [PMID: 37437103 DOI: 10.1002/jbt.23455] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 06/14/2023] [Accepted: 06/29/2023] [Indexed: 07/14/2023]
Abstract
The influence of modern lifestyle, diet, exposure to chemicals such as phytosanitary substances, together with sedentary lifestyles and lack of exercise play an important role in inducing reactive stress (RS) and disease. The imbalance in the production and scavenging of free radicals and the induction of RS (oxidative, nitrosative, and halogenative) plays an essential role in the etiology of various chronic pathologies, such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. The implication of free radicals and reactive species injury in metabolic disturbances and the onset of many diseases have been accumulating for several decades, and are now accepted as a major cause of many chronic diseases. Exposure to elevated levels of free radicals can cause molecular structural impact on proteins, lipids, and DNA, as well as functional alteration of enzyme homeostasis, leading to aberrations in gene expression. Endogenous depletion of antioxidant enzymes can be mitigated using exogenous antioxidants. The current interest in the use of exogenous antioxidants as adjunctive agents for the treatment of human diseases allows a better understanding of these diseases, facilitating the development of new therapeutic agents with antioxidant activity to improve the treatment of various diseases. Here we examine the role that RS play in the initiation of disease and in the reactivity of free radicals and RS in organic and inorganic cellular components.
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Affiliation(s)
| | | | - Celia Andrés Juan
- Department of Organic Chemistry, Cinquima Institute, Faculty of Sciences, Valladolid University, Valladolid, Spain
| | - Francisco J Plou
- Institute of Catalysis and Petrochemistry, CSIC-Spanish Research Council, Madrid, Spain
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Nazem MR, Asadi M, Adelipour M, Jabbari N, Allameh A. Zinc supplementation ameliorates type 2 diabetes markers through the enhancement of total antioxidant capacity in overweight patients. Postgrad Med J 2023; 99:862-867. [PMID: 37137539 DOI: 10.1136/postgradmedj-2021-140878] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 04/07/2022] [Indexed: 12/04/2022]
Abstract
BACKGROUND Evidence show that the recommended dose of zinc may not be sufficient for controlling pathological conditions such as type 2 diabetes mellitus (T2DM). AIM This study aimed to evaluate the effects of zinc supplementation on the oxidative status in overweight T2DM. In addition, the routine glycaemic parameters were determined and compared in zinc-treated and placebo groups. METHODS In this randomised, double-blind, placebo-controlled trial, 70 patients with T2DM were selected. They were divided into two groups for supplementation of 50 mg zinc gluconate or placebo (zinc group, n=35; placebo group, n=35) per day for 8 weeks. Blood samples were collected from all the individuals in the zinc group and controls for analysis. RESULTS The results showed that zinc supplementation to patients with T2DM for 8 weeks significantly inhibited serum levels of lipid peroxidation (25%), nitrotyrosine (30%) and total oxidant status levels (25%, p<0.05). Nevertheless, the total antioxidant capacity was significantly elevated (16%) following zinc intake by patients with T2DM. CONCLUSIONS These data, together with our previous report, may suggest that the control in the glycaemic condition in overweight patients with T2DM is correlated with the antioxidative/oxidative balance following intake of 50 mg zinc supplementation for 8 weeks. Under these circumstances, the clinical and glycaemic indices, including fasting blood glucose, insulin, haemoglobin A1c and homeostasis model of assessment-insulin resistance, were controlled. TRIAL REGISTRATION NUMBER IRCT2015083102.
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Affiliation(s)
- Mohammad Reza Nazem
- Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran (the Islamic Republic of)
| | - Mojgan Asadi
- Department of Clinical Biochemistry, Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Tehran, Iran (the Islamic Republic of)
| | - Maryam Adelipour
- Department of Clinical Biochemistry, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran (the Islamic Republic of)
| | - Niloofar Jabbari
- Department of Clinical Pharmacy, IAUPS, Tehran, Iran (the Islamic Republic of)
| | - Abdolamir Allameh
- Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran (the Islamic Republic of)
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Ning L, Bai Y, Wang Z, Wen W, Wang J. Label-free electrochemiluminescence immunosensor based on conductive PANI to synergistically amplify electrodeposited AuNPs luminophore signal for ultrasensitive detection of 3-nitrotyrosine. Microchem J 2023. [DOI: 10.1016/j.microc.2023.108619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
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Grune T, Schnell V, Jung T. High glucose leads to redistribution of the proteasomal system. Biofactors 2023. [PMID: 36757058 DOI: 10.1002/biof.1937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 12/27/2022] [Indexed: 02/10/2023]
Abstract
The impact of high glucose on the cellular redox state, causing both induction of antioxidative systems and also enhanced protein oxidation is discussed for a long time. It is established that elevated glucose levels are disrupting the cellular proteostasis and influencing the proteasomal system. However, it is still unresolved whether this is due to a reaction of the cellular proteasomal system towards the high glucose or whether this is a secondary reaction to inflammatory stimuli. Therefore, we used a dermal fibroblast cell line exposed to high glucose in order to reveal whether a response of the proteasomal system takes place. We investigated the α4 and the inducible iβ5 subunits of the 20S proteasome, as well as the Rpn1-subunit of the 19S proteasomal regulator complex, measured activity of the 20S, 20S1, and 26S proteasome and detected as well changes in expression as a redistribution into the nucleus. Interestingly, while the activity of the proteasomal forms rather decreased under high glucose treatment; higher expression levels of components of the proteasomal system and higher concentrations of protein-bound 3-nitrotyrosine and Nrf2 (nuclear factor [erythroid-derived 2]-like 2) were detected. However, no change in the cytosol-nucleus distribution could be detected for most of the quantified parameters. We concluded that high glucose alone, without additional inflammatory stimuli, provokes a regulatory response on the ubiquitin-proteasomal system.
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Affiliation(s)
- Tilman Grune
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- German Center for Cardiovascular Research (DZHK), Berlin, Germany
- Institute of Nutrition, University of Potsdam, Nuthetal, Germany
- Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Vanessa Schnell
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Tobias Jung
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
- German Center for Cardiovascular Research (DZHK), Berlin, Germany
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Karmakar S, Das TK, Kalarikkal N, Saha A. A Simplified Approach for the Aqueous Synthesis of Luminescent CdSe/ZnS Core/Shell Quantum Dots and Their Applications in Ultrasensitive Determination of the Biomarker 3-Nitro-l-tyrosine. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2022; 38:15995-16003. [PMID: 36512759 DOI: 10.1021/acs.langmuir.2c02459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
In contrast to the hot-injection organometallic routes, synthesizing stable and highly luminescent core/shell nanocrystals with encapsulation of biocompatible groups through an aqueous route is a long-standing challenge. In recent years, relatively high quantum efficiency and unique properties of core/shell nanostructured materials (quantum dots) have contributed toward enhancement in sensing capability. The present work reports a facile aqueous synthesis process of core/shell CdSe/ZnS quantum dots (QDs) with encapsulation of glutathione (GSH). The optimal conditions for the synthesis of the most stable particles were ascertained, and the different experimental analyses suggest that the stable core/shell QDs in question have good crystallinity with a size around 4.7 nm with a shell thickness of 0.7 nm and a photoluminescence quantum yield of about 35%. Further, it is demonstrated that the as-synthesized material has great potential in detecting as low as 0.28 nM 3-nitro-l-tyrosine (3-NT), an important marker for oxidative stress, the level of which in our body signals several chronically diseased conditions. The enthalpy-driven interactions of CdSe/ZnS-GSH QDs with 3-NT were characterized through steady-state and time-resolved luminescence spectroscopy and isothermal microcalorimetry. The devised method of probing 3-NT was further validated with human serum samples. Thus, the proposed strategy may provide a protocol for selective determination of 3-NT under different pathological conditions.
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Affiliation(s)
- Sudip Karmakar
- UGC-DAE Consortium for Scientific Research, Kolkata Centre, III/LB-8 Bidhannagar, Kolkata700106, India
| | - Tushar Kanti Das
- UGC-DAE Consortium for Scientific Research, Kolkata Centre, III/LB-8 Bidhannagar, Kolkata700106, India
| | - Nandakumar Kalarikkal
- School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam686560, Kerala, India
| | - Abhijit Saha
- UGC-DAE Consortium for Scientific Research, Kolkata Centre, III/LB-8 Bidhannagar, Kolkata700106, India
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Impact of Reactive Species on Amino Acids-Biological Relevance in Proteins and Induced Pathologies. Int J Mol Sci 2022; 23:ijms232214049. [PMID: 36430532 PMCID: PMC9692786 DOI: 10.3390/ijms232214049] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
This review examines the impact of reactive species RS (of oxygen ROS, nitrogen RNS and halogens RHS) on various amino acids, analyzed from a reactive point of view of how during these reactions, the molecules are hydroxylated, nitrated, or halogenated such that they can lose their capacity to form part of the proteins or peptides, and can lose their function. The reactions of the RS with several amino acids are described, and an attempt was made to review and explain the chemical mechanisms of the formation of the hydroxylated, nitrated, and halogenated derivatives. One aim of this work is to provide a theoretical analysis of the amino acids and derivatives compounds in the possible positions. Tyrosine, methionine, cysteine, and tryptophan can react with the harmful peroxynitrite or •OH and •NO2 radicals and glycine, serine, alanine, valine, arginine, lysine, tyrosine, histidine, cysteine, methionine, cystine, tryptophan, glutamine and asparagine can react with hypochlorous acid HOCl. These theoretical results may help to explain the loss of function of proteins subjected to these three types of reactive stresses. We hope that this work can help to assess the potential damage that reactive species can cause to free amino acids or the corresponding residues when they are part of peptides and proteins.
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Meka Farid Babu, A.R. S, Benerji G.V.. 3-Nitrotyrosine (NT) levels in serum and its association with insulin resistance in patients with type 2 diabetes mellitus: Biomarker role of NT in the assessment of oxidative stress mediated impending vascular complications in nephropathy. Biomedicine (Taipei) 2022. [DOI: 10.51248/.v42i4.1433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Introduction and Aim: 3-Nitrotyrosine (NT) has been recognized as a marker of oxidative stress in diabetes mellitus. NT has also been studied in diverse metabolic conditions. The aim of our study was oriented towards the role of NT as a predictor of oxidative stress mediated impending nephropathy in diabetes mellitus and that with reference to albuminuria.
Materials and Methods: A total of 150 type 2 diabetics in the age group 35 - 50 years were enrolled as three groups, comprising 50 each, based on albuminuria. 50 healthy age and gender matched subjects constituted the control group. Serum NT and Insulin were assessed by ELISA. HbA1c was quantitated by immunoturbidimetric method and microalbumin was assessed by turbilatex method. Routine biochemistry was enabled through ERBA EM-200 fully automated analyzer. Stringent quality control was affected. The study was begun following approval accorded by the competent committees.
Results: NT levels were positively correlated with albumin-creatinine ratio and insulin resistance. NT could be used as a predictor of impending vascular complications in diabetic nephropathy.
Conclusion: NT levels could act as a predictor of oxidative stress mediated diabetic nephropathy in the light of albuminuria.
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12
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Role of Oxidative Stress in the Pathogenesis of Atherothrombotic Diseases. Antioxidants (Basel) 2022; 11:antiox11071408. [PMID: 35883899 PMCID: PMC9312358 DOI: 10.3390/antiox11071408] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 07/12/2022] [Accepted: 07/19/2022] [Indexed: 12/04/2022] Open
Abstract
Oxidative stress is generated by the imbalance between reactive oxygen species (ROS) formation and antioxidant scavenger system’s activity. Increased ROS, such as superoxide anion, hydrogen peroxide, hydroxyl radical and peroxynitrite, likely contribute to the development and complications of atherosclerotic cardiovascular diseases (ASCVD). In genetically modified mouse models of atherosclerosis, the overexpression of ROS-generating enzymes and uncontrolled ROS formation appear to be associated with accelerated atherosclerosis. Conversely, the overexpression of ROS scavenger systems reduces or stabilizes atherosclerotic lesions, depending on the genetic background of the mouse model. In humans, higher levels of circulating biomarkers derived from the oxidation of lipids (8-epi-prostaglandin F2α, and malondialdehyde), as well as proteins (oxidized low-density lipoprotein, nitrotyrosine, protein carbonyls, advanced glycation end-products), are increased in conditions of high cardiovascular risk or overt ASCVD, and some oxidation biomarkers have been reported as independent predictors of ASCVD in large observational cohorts. In animal models, antioxidant supplementation with melatonin, resveratrol, Vitamin E, stevioside, acacetin and n-polyunsaturated fatty acids reduced ROS and attenuated atherosclerotic lesions. However, in humans, evidence from large, placebo-controlled, randomized trials or prospective studies failed to show any athero-protective effect of antioxidant supplementation with different compounds in different CV settings. However, the chronic consumption of diets known to be rich in antioxidant compounds (e.g., Mediterranean and high-fish diet), has shown to reduce ASCVD over decades. Future studies are needed to fill the gap between the data and targets derived from studies in animals and their pathogenetic and therapeutic significance in human ASCVD.
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Thomas C, Wurzer L, Malle E, Ristow M, Madreiter-Sokolowski CT. Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs. FRONTIERS IN AGING 2022; 3:905261. [PMID: 35821802 PMCID: PMC9261327 DOI: 10.3389/fragi.2022.905261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 05/18/2022] [Indexed: 01/17/2023]
Abstract
Age-associated diseases represent a growing burden for global health systems in our aging society. Consequently, we urgently need innovative strategies to counteract these pathological disturbances. Overwhelming generation of reactive oxygen species (ROS) is associated with age-related damage, leading to cellular dysfunction and, ultimately, diseases. However, low-dose ROS act as crucial signaling molecules and inducers of a vaccination-like response to boost antioxidant defense mechanisms, known as mitohormesis. Consequently, modulation of ROS homeostasis by nutrition, exercise, or pharmacological interventions is critical in aging. Numerous nutrients and approved drugs exhibit pleiotropic effects on ROS homeostasis. In the current review, we provide an overview of drugs affecting ROS generation and ROS detoxification and evaluate the potential of these effects to counteract the development and progression of age-related diseases. In case of inflammation-related dysfunctions, cardiovascular- and neurodegenerative diseases, it might be essential to strengthen antioxidant defense mechanisms in advance by low ROS level rises to boost the individual ROS defense mechanisms. In contrast, induction of overwhelming ROS production might be helpful to fight pathogens and kill cancer cells. While we outline the potential of ROS manipulation to counteract age-related dysfunction and diseases, we also raise the question about the proper intervention time and dosage.
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Affiliation(s)
- Carolin Thomas
- Laboratory of Energy Metabolism Institute of Translational Medicine Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland
| | - Lia Wurzer
- Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Ernst Malle
- Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Michael Ristow
- Laboratory of Energy Metabolism Institute of Translational Medicine Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland
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14
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Singh A, Kukreti R, Saso L, Kukreti S. Mechanistic Insight into Oxidative Stress-Triggered Signaling Pathways and Type 2 Diabetes. Molecules 2022; 27:950. [PMID: 35164215 PMCID: PMC8840622 DOI: 10.3390/molecules27030950] [Citation(s) in RCA: 139] [Impact Index Per Article: 46.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 01/20/2022] [Accepted: 01/26/2022] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress (OS) is a metabolic dysfunction mediated by the imbalance between the biochemical processes leading to elevated production of reactive oxygen species (ROS) and the antioxidant defense system of the body. It has a ubiquitous role in the development of numerous noncommunicable maladies including cardiovascular diseases, cancers, neurodegenerative diseases, aging and respiratory diseases. Diseases associated with metabolic dysfunction may be influenced by changes in the redox balance. Lately, there has been increasing awareness and evidence that diabetes mellitus (DM), particularly type 2 diabetes, is significantly modulated by oxidative stress. DM is a state of impaired metabolism characterized by hyperglycemia, resulting from defects in insulin secretion or action, or both. ROS such as hydrogen peroxide and the superoxide anion introduce chemical changes virtually in all cellular components, causing deleterious effects on the islets of β-cells, in turn affecting insulin production. Under hyperglycemic conditions, various signaling pathways such as nuclear factor-κβ (NF-κβ) and protein kinase C (PKC) are also activated by ROS. All of these can be linked to a hindrance in insulin signaling pathways, leading to insulin resistance. Hyperglycemia-induced oxidative stress plays a substantial role in complications including diabetic nephropathy. DM patients are more prone to microvascular as well as atherosclerotic macrovascular diseases. This systemic disease affects most countries around the world, owing to population explosion, aging, urbanization, obesity, lifestyle, etc. However, some modulators, with their free radical scavenging properties, can play a prospective role in overcoming the debilitating effects of OS. This review is a modest approach to summarizing the basics and interlinkages of oxidative stress, its modulators and diabetes mellitus. It may add to the understanding of and insight into the pathophysiology of diabetes and the crucial role of antioxidants to weaken the complications and morbidity resulting from this chronic disease.
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Affiliation(s)
- Anju Singh
- Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India;
- Department of Chemistry, Ramjas College, University of Delhi, Delhi 110007, India
| | - Ritushree Kukreti
- Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology (IGIB), Mall Road, Delhi 110007, India;
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy;
| | - Shrikant Kukreti
- Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India;
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ALPTEKİN Ö, TUKEL SS, TURAN B, KUYUCU Y. Alterations in Antioxidant Defence Systems and Metal Profiles in Liver of Rats with Metabolic Syndrome Induced with High-Sucrose Diet. JOURNAL OF THE TURKISH CHEMICAL SOCIETY, SECTION A: CHEMISTRY 2021. [DOI: 10.18596/jotcsa.945582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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16
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Marmentini C, Branco RCS, Boschero AC, Kurauti MA. Islet amyloid toxicity: From genesis to counteracting mechanisms. J Cell Physiol 2021; 237:1119-1142. [PMID: 34636428 DOI: 10.1002/jcp.30600] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 09/09/2021] [Accepted: 10/01/2021] [Indexed: 11/11/2022]
Abstract
Islet amyloid polypeptide (IAPP or amylin) is a hormone co-secreted with insulin by pancreatic β-cells and is the major component of islet amyloid. Islet amyloid is found in the pancreas of patients with type 2 diabetes (T2D) and may be involved in β-cell dysfunction and death, observed in this disease. Thus, investigating the aspects related to amyloid formation is relevant to the development of strategies towards β-cell protection. In this sense, IAPP misprocessing, IAPP overproduction, and disturbances in intra- and extracellular environments seem to be decisive for IAPP to form islet amyloid. Islet amyloid toxicity in β-cells may be triggered in intra- and/or extracellular sites by membrane damage, endoplasmic reticulum stress, autophagy disruption, mitochondrial dysfunction, inflammation, and apoptosis. Importantly, different approaches have been suggested to prevent islet amyloid cytotoxicity, from inhibition of IAPP aggregation to attenuation of cell death mechanisms. Such approaches have improved β-cell function and prevented the development of hyperglycemia in animals. Therefore, counteracting islet amyloid may be a promising therapy for T2D treatment.
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Affiliation(s)
- Carine Marmentini
- Laboratory of Endocrine Pancreas and Metabolism, Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
| | - Renato C S Branco
- Laboratory of Endocrine Pancreas and Metabolism, Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
| | - Antonio C Boschero
- Laboratory of Endocrine Pancreas and Metabolism, Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
| | - Mirian A Kurauti
- Laboratory of Endocrine Pancreas and Metabolism, Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil.,Department of Physiological Sciences, Biological Sciences Center, State University of Maringa (UEM), Maringa, Brazil
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17
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Aboalgasm H, Ballo R, Gwanyanya A. Organisational alteration of cardiac myofilament proteins by hyperglycaemia in mouse embryonic stem cell-derived cardiomyocytes. J Muscle Res Cell Motil 2021; 42:419-428. [PMID: 34387802 DOI: 10.1007/s10974-021-09607-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/04/2021] [Indexed: 11/28/2022]
Abstract
The exposure of the developing foetal heart to hyperglycaemia in mothers with diabetes mellitus is a major risk factor for foetal cardiac complications that lead to heart failure. We studied the effects of hyperglycaemia on the layout of cardiac myofilament proteins in stem cell-derived cardiomyocytes and their possible underlying mechanisms. Mouse embryonic stem cells (mESCs) were differentiated into cardiac-like cells and cultured in media containing baseline- or high glucose concentrations. Cellular biomarkers were detected using Western blot analysis, immunocytochemistry, 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay, and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. High glucose decreased the proportion of cardiac troponin T and α-actinin 2 positive mESCs as well as disrupted the α-actinin 2 striated pattern and the distribution of the cardiac myosin heavy chain α- and β isoforms. However, there was no alteration of the cellular EdU uptake nor the expression of the receptor of advanced glycation end-product (RAGE). High glucose also increased the presence of the oxidative stress marker nitrotyrosine as well as the number of TUNEL-stained nuclei in cardiac-like cells. Treatment with the antioxidant N-acetyl cysteine decreased the number of TUNEL-stained cells in high glucose and improved the α-actinin 2 striated pattern. Hyperglycaemia negatively impacted the expression and cellular organisation of cardiac myofilament proteins in mESC-derived cardiomyocytes through oxidative stress. The results add further insights into the pathophysiological mechanisms of cardiac contractile dysfunction in diabetic cardiac developmental disease.
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Affiliation(s)
- Hamida Aboalgasm
- Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
| | - Robea Ballo
- Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
| | - Asfree Gwanyanya
- Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa.
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18
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Zahra KF, Lefter R, Ali A, Abdellah EC, Trus C, Ciobica A, Timofte D. The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:9965916. [PMID: 34394838 PMCID: PMC8360750 DOI: 10.1155/2021/9965916] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 07/19/2021] [Indexed: 12/24/2022]
Abstract
Oxygen-free radicals, reactive oxygen species (ROS) or reactive nitrogen species (RNS), are known by their "double-sided" nature in biological systems. The beneficial effects of ROS involve physiological roles as weapons in the arsenal of the immune system (destroying bacteria within phagocytic cells) and role in programmed cell death (apoptosis). On the other hand, the redox imbalance in favor of the prooxidants results in an overproduction of the ROS/RNS leading to oxidative stress. This imbalance can, therefore, be related to oncogenic stimulation. High levels of ROS disrupt cellular processes by nonspecifically attacking proteins, lipids, and DNA. It appears that DNA damage is the key player in cancer initiation and the formation of 8-OH-G, a potential biomarker for carcinogenesis. The harmful effect of ROS is neutralized by an antioxidant protection treatment as they convert ROS into less reactive species. However, contradictory epidemiological results show that supplementation above physiological doses recommended for antioxidants and taken over a long period can lead to harmful effects and even increase the risk of cancer. Thus, we are describing here some of the latest updates on the involvement of oxidative stress in cancer pathology and a double view on the role of the antioxidants in this context and how this could be relevant in the management and pathology of cancer.
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Affiliation(s)
- Kamal Fatima Zahra
- Faculty of Sciences and Techniques, Laboratory of Physical Chemistry of Processes and Materials/Agri-Food and Health, Hassan First University, B.P. 539, 26000 Settat, Morocco
| | - Radu Lefter
- Center of Biomedical Research, Romanian Academy, 8th Carol I Avenue, 700506 Iasi, Romania
| | - Ahmad Ali
- Department of Life Sciences, University of Mumbai, Vidyanagari, Santacruz (East), Mumbai 400098, India
| | - Ech-Chahad Abdellah
- Faculty of Sciences and Techniques, Laboratory of Physical Chemistry of Processes and Materials, Hassan First University, B.P. 539, 26000 Settat, Morocco
| | - Constantin Trus
- Department of Morphological and Functional Sciences, Faculty of Medicine, Dunarea de Jos University, 800008 Galati, Romania
| | - Alin Ciobica
- Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University, 11th Carol I Avenue, 700506 Iasi, Romania
| | - Daniel Timofte
- Faculty of Medicine, “Grigore T. Popa”, University of Medicine and Pharmacy, Strada Universitatii 16, 700115 Iasi, Romania
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19
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Real time detection of 3-nitrotyrosine using smartphone-based electrochemiluminescence. Biosens Bioelectron 2021; 187:113284. [PMID: 34022499 DOI: 10.1016/j.bios.2021.113284] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 01/31/2023]
Abstract
As an oxidase stress biomarker, 3-nitrotyrosine is closely associated with many cardiovascular diseases. Thus, early diagnosis and real time detection of 3-nitrotyrosine at bedside are highly important. Herein, we developed a handheld electrochemiluminescence (ECL) analysis device, which integrates printed circuit board (PCB) for electrical stimulation and smartphone for optical signals readout. Fast and accurate determination of 3-nitrotyrosine was achieved with Antibody/Ru(dcpy)32+@AuNPs/MoS2 modified Au electrode (Ab/Ru@AuNPs/MoS2) for ECL analysis. The linear range of 3-nitrotyrosine detection was from 10-8 mol/L to 10-6 mol/L with a detection limit of 8.4 × 10-9 mol/L. In addition, an Android application was developed to realize real time analysis of ECL emissions and results readout for detection. To confirm the usage of the device, spiked serum with different concentrations was tested and the results indicated the practical reliability and stability of this device. The operating procedure for ECL analysis in this device is extremely easy and electrical stimulation was adjustable from 0 V to 5 V for general ECL systems. Thus, we believe this handheld device for ECL analysis has extensive prospects for application in Point-of-care testing and health caring.
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20
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Bala CG, Rusu A, Ciobanu D, Bucsa C, Roman G. Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research. Antioxidants (Basel) 2021; 10:610. [PMID: 33921149 PMCID: PMC8071553 DOI: 10.3390/antiox10040610] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/11/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023] Open
Abstract
Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1-Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism.
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Affiliation(s)
- Cornelia G. Bala
- Department of Diabetes and Nutrition Diseases, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.G.B.); (D.C.); (G.R.)
| | - Adriana Rusu
- Department of Diabetes and Nutrition Diseases, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.G.B.); (D.C.); (G.R.)
| | - Dana Ciobanu
- Department of Diabetes and Nutrition Diseases, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.G.B.); (D.C.); (G.R.)
| | - Camelia Bucsa
- Drug Information Research Centre, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Gabriela Roman
- Department of Diabetes and Nutrition Diseases, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.G.B.); (D.C.); (G.R.)
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21
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Seong SH, Jung HA, Choi JS. Discovery of Flazin, an Alkaloid Isolated from Cherry Tomato Juice, As a Novel Non-Enzymatic Protein Glycation Inhibitor via in Vitro and in Silico Studies. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:3647-3657. [PMID: 33739098 DOI: 10.1021/acs.jafc.0c07486] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Both overproduced reactive oxygen species/reactive nitrogen species and hyperglycemic conditions accompany a significant increase in protein glycation and nitration that contribute to the initiation and progression of diabetic complications and neuronal disorders. In this study, 19 compounds, including steroidal saponins, alkaloids, cerebroside, phenolic compounds, sterols, and nucleosides, were isolated from cherry tomato (Solanum lycopersicum var. cerasiforme) juice, of which flazin showed good inhibition on monosaccharide-induced non-enzymatic bovine pancreas insulin and bovine serum albumin (BSA) glycation. Molecular dynamics simulations revealed that flazin continuously interacts with Phe1, Val2, Tyr26, and Lys29 insulin residues, which play a key role in insulin glycation/dimerization. In addition, depending upon the flazin dose, this blocked the tyrosine nitration of BSA via scavenging peroxynitrite anions. Taken together, our novel findings suggest that flazin could be a lead compound for the treatment of diabetes and neuronal disorders via the inhibition of non-enzymatic protein glycation and the elimination of peroxynitrite.
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Affiliation(s)
- Su Hui Seong
- Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea
| | - Hyun Ah Jung
- Department of Food Science and Human Nutrition, Jeonbuk National University, Jeonju 54896, Republic of Korea
| | - Jae Sue Choi
- Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea
- Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea
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Insulin-Mimetic Dihydroxanthyletin-Type Coumarins from Angelica decursiva with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms. Antioxidants (Basel) 2021; 10:antiox10020292. [PMID: 33672051 PMCID: PMC7919472 DOI: 10.3390/antiox10020292] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 01/04/2023] Open
Abstract
As a traditional medicine, Angelica decursiva has been used for the treatment of many diseases. The goal of this study was to evaluate the potential of four natural major dihydroxanthyletin-type coumarins—(+)-trans-decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III—to inhibit the enzymes, protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. In the kinetic study of the PTP1B enzyme’s inhibition, we found that (+)-trans-decursidinol, Pd-C-I, and Pd-C-II led to competitive inhibition, while Pd-C-III displayed mixed-type inhibition. Moreover, (+)-trans-decursidinol exhibited competitive-type, and Pd-C-I and Pd-C-II mixed-type, while Pd-C-III showed non-competitive type inhibition of α-glucosidase. Docking simulations of these coumarins showed negative binding energies and a similar proximity to residues in the PTP1B and α-glucosidase binding pocket, which means they are closely connected and strongly binding with the active enzyme site. In addition, dihydroxanthyletin-type coumarins are up to 40 µM non-toxic in HepG2 cells and have substantially increased glucose uptake and decreased expression of PTP1B in insulin-resistant HepG2 cells. Further, coumarins inhibited ONOO−-mediated albumin nitration and scavenged peroxynitrite (ONOO−), and reactive oxygen species (ROS). Our overall findings showed that dihydroxanthyletin-type coumarins derived from A. decursiva is used as a dual inhibitor for enzymes, such as PTP1B and α-glucosidase, as well as for insulin susceptibility.
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Williamson-Reisdorph CM, Quindry TS, Tiemessen KG, Cuddy J, Hailes W, Slivka D, Ruby BC, Quindry JC. Blood oxidative stress and post-exercise recovery are unaffected byhypobaric and hypoxic environments. J Sports Sci 2021; 39:1356-1365. [PMID: 33423613 DOI: 10.1080/02640414.2021.1872960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Hypobaria and hypoxia exert independent effects on oxidative stress during exercise, while combined effectson the post-exercise recovery period remain unclear.Accordingly, this study examined the recovery period during lab-simulated hypoxic and hypobaric conditions following exercise-induced oxidative stress. Participants (n=13) performed 60-minutes of cycling (70% watts max) in a normobaric normoxic environment followed by a four-hour recovery under three conditions; 1000m normobaric normoxia (NN, 675mmHg), 4400m normobaric hypoxia (NH, 675mmHg), or 4400m hypobaric hypoxia (HH, 440mmHg). Blood samples collected at Pre, Post, 2-Hours (2-HR), and 4-Hours (4-HR) post-exercise were analyzed fora potential increase in biochemical modifications of proteins(protein carbonyls, PC; 3-nitrotyrosines, 3NT) lipids (lipid hydroperoxides, LOOH; 8-isoprostanes, 8-ISO), and antioxidant capacity (FRAP, TEAC). Gene transcripts (EPAS, HMOX1, SOD2, NFE2L2) were quantified by qRT-PCR from muscle biopsies taken Pre and Post exercise. Hypoxia and hypobaria had no effect throughout recovery. Post-exercise TEAC (p=0.041), FRAP (p=0.013), and 8-ISO (p=0.044) increased, while PC (p=0.002) and 3-NT (p=0.032) were decreased. LOOH was lower in Post (p=0.018) NH trial samples. Exercise-dependent increases occurred in NFE2L2 (p=0.003), HMXO1 (p<0.001), SOD2 (p=0.046), and EPAS (p=0.038). Exercise recovery under conditions of NH and HH did not impact blood oxidative stress or redox-sensitive gene transcripts.
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Affiliation(s)
| | - Tiffany S Quindry
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT, USA
| | - Kathryn G Tiemessen
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT, USA
| | - John Cuddy
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT, USA
| | - Walter Hailes
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT, USA
| | - Dustin Slivka
- School of Health and Kinesiology, University of Nebraska - Omaha, Omaha, NE, USA
| | - Brent C Ruby
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT, USA
| | - John C Quindry
- School of Integrative Physiology and Athletic Training, University of Montana, Missoula, MT, USA
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Kim G, Lim S, Kwon H, Park IB, Ahn KJ, Park C, Kwon SK, Kim HS, Park SW, Kim SG, Moon MK, Kim ES, Chung CH, Park KS, Kim M, Chung DJ, Lee CB, Kim TH, Lee M. Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active-controlled, randomized, double-blind study with open-label extension (the EVERGREEN study). Diabetes Obes Metab 2020; 22:1527-1536. [PMID: 32319168 PMCID: PMC7496811 DOI: 10.1111/dom.14061] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 04/13/2020] [Accepted: 04/15/2020] [Indexed: 02/07/2023]
Abstract
AIM To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes. MATERIALS AND METHODS In this 12-week, multicentre, randomized, double-blind, active-controlled, and 12-week open-label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%-10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92). RESULTS After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was -0.85% and -0.75%, respectively. The between-group difference was -0.10% (95% CI: -0.32 to 0.11), showing non-inferiority based on a non-inferiority margin of 0.4%. The change in MAGE was -24.6 mg/dL in the evogliptin group and -16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by -0.94%, with HbA1c values of <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks. CONCLUSION In this study, the glucose-lowering efficacy of evogliptin was non-inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycaemic variability without causing any serious adverse events in patients with type 2 diabetes.
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Affiliation(s)
- Gyuri Kim
- Department of Medicine, Samsung Medical CenterSungkyunkwan UniversitySeoulKorea
| | - Soo Lim
- Department of Internal Medicine, Seoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Hyuk‐Sang Kwon
- Department of Internal Medicine, Yeouido St. Mary's Hospital, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Ie B. Park
- Department of Internal MedicineGachon University Gil Medical CenterIncheonKorea
| | - Kyu J. Ahn
- Department of Internal MedicineKangdong Kyung Hee University HospitalSeoulKorea
| | - Cheol‐Young Park
- Department of Internal MedicineKangbuk Samsung HospitalSeoulKorea
| | - Su K. Kwon
- Department of Internal MedicineKosin University Gospel HospitalBusanKorea
| | - Hye S. Kim
- Department of Internal MedicineKeimyung University Dongsan Medical CenterDaeguKorea
| | - Seok W. Park
- Department of Internal MedicineYonsei University College of MedicineSeoulKorea
| | - Sin G. Kim
- Department of Internal MedicineKorea University Anam HospitalSeoulKorea
| | - Min K. Moon
- Department of Internal MedicineSeoul National University Boramae Medical CenterSeoulKorea
| | - Eun S. Kim
- Department of Internal Medicine, Ulsan University HospitalCollege of Medicine University of UlsanUlsanKorea
| | - Choon H. Chung
- Department of Internal MedicineWonju Severance Christian HospitalWonjuKorea
| | - Kang S. Park
- Department of Internal MedicineEulji University HospitalDaejeonKorea
| | - Mikyung Kim
- Department of Internal MedicineInje University Haeundae Paik HospitalBusanKorea
| | - Dong J. Chung
- Department of Internal Medicine, Chonnam National University Medical SchoolChonnam National University HospitalGwangjuKorea
| | - Chang B. Lee
- Department of Internal MedicineHanyang University Guri HospitalGuriKorea
| | - Tae H. Kim
- Department of Internal MedicineSeoul Medical CenterSeoulKorea
| | - Moon‐Kyu Lee
- Department of Internal MedicineSoonchunhyang University Gumi HospitalGumiSouth Korea
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Zhang A, Fang H, Chen J, He L, Chen Y. Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy. Front Physiol 2020; 11:1064. [PMID: 32982792 PMCID: PMC7488177 DOI: 10.3389/fphys.2020.01064] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 07/31/2020] [Indexed: 12/12/2022] Open
Abstract
Diabetic nephropathy (DN) is an important public health concern of increasing proportions and the leading cause of end-stage renal disease (ESRD) in diabetic patients. It is one of the most common long-term microvascular complications of diabetes mellitus that is characterized by proteinuria and glomerular structural changes. Angiogenesis has long been considered to contribute to the pathogenesis of DN, whereas the molecular mechanisms of which are barely known. Angiogenic factors associated with angiogenesis are the major candidates to explain the microvascular and pathologic finds of DN. Vascular endothelial growth factor A (VEGF-A), leucine-rich α-2-glycoprotein 1, angiopoietins and vasohibin family signal between the podocytes, endothelium, and mesangium have important roles in the maintenance of renal functions. An appropriate amount of VEGF-A is beneficial to maintaining glomerular structure, while excessive VEGF-A can lead to abnormal angiogenesis. LRG1 is a novel pro-angiogenic factors involved in the abnormal angiogenesis and renal fibrosis in DN. The imbalance of Ang1/Ang2 ratio has a role in leading to glomerular disease. Vasohibin-2 is recently shown to be in diabetes-induced glomerular alterations. This review will focus on current understanding of these angiogenic factors in angiogenesis and pathogenesis associated with the development of DN, with the aim of evaluating the potential of anti-angiogenesis therapy in patients with DN.
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Affiliation(s)
- Afei Zhang
- Department of Nephrology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Huawei Fang
- Department of Nephrology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Jie Chen
- Department of Nephrology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Leyu He
- Department of Nephrology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Youwei Chen
- Department of Nephrology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
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Samson F, He W, Sripathi SR, Patrick AT, Madu J, Chung H, Frost MC, Jee D, Gutsaeva DR, Jahng WJ. Dual Switch Mechanism of Erythropoietin as an Antiapoptotic and Pro-Angiogenic Determinant in the Retina. ACS OMEGA 2020; 5:21113-21126. [PMID: 32875248 PMCID: PMC7450639 DOI: 10.1021/acsomega.0c02763] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 07/28/2020] [Indexed: 05/07/2023]
Abstract
Constant or intense light degenerates the retina and retinal pigment epithelial cells. Light generates reactive oxygen species and nitric oxide leading to initial reactions of retinal degeneration. Apoptosis is the primary mechanism of abnormal death of photoreceptors, retinal ganglion cells, or retinal pigment epithelium (RPE) in degenerative retinal diseases, including diabetic retinopathy and age-related macular degeneration. The current study evaluated the function of erythropoietin (EPO) on angiogenesis and apoptosis in the retina and RPE under oxidative stress. We determined the pro-angiogenic and antiapoptotic mechanism of EPO under stress conditions using a conditional EPO knockdown model using siRNA, EPO addition, proteomics, immunocytochemistry, and bioinformatic analysis. Our studies verified that EPO protected retinal cells from light-, hypoxia-, hyperoxia-, and hydrogen peroxide-induced apoptosis through caspase inhibition, whereas up-regulated angiogenic reactions through vascular endothelial growth factor (VEGF) and angiotensin pathway. We demonstrated that the EPO expression in the retina and subsequent serine/threonine/tyrosine kinase phosphorylations might be linked to oxidative stress response tightly to determining angiogenesis and apoptosis. Neuroprotective roles of EPO may involve the balance between antiapoptotic and pro-angiogenic signaling molecules, including BCL-xL, c-FOS, caspase-3, nitric oxide, angiotensin, and VEGF receptor. Our data indicate a new therapeutic application of EPO toward retinal degeneration based on the dual roles in apoptosis and angiogenesis at the molecular level under oxidative stress.
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Affiliation(s)
| | - Weilue He
- Department
of Biomedical Engineering, Michigan Technological
University, Houghton 49931, United States
| | - Srinivas R. Sripathi
- Department
of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
| | - Ambrose Teru Patrick
- Department
of Petroleum Chemistry, American University
of Nigeria, Yola 640101, Nigeria
| | - Joshua Madu
- Department
of Petroleum Chemistry, American University
of Nigeria, Yola 640101, Nigeria
| | - Hyewon Chung
- Department
of Ophthalmology, School of Medicine, Konkuk
University, Seoul 05030, Korea
| | - Megan C. Frost
- Department
of Biomedical Engineering, Michigan Technological
University, Houghton 49931, United States
| | - Donghyun Jee
- Division
of Vitreous and Retina, Department of Ophthalmology, St. Vincent’s
Hospital, College of Medicine, The Catholic
University of Korea, Suwon 16247, Korea
| | - Diana R. Gutsaeva
- Department
of Ophthalmology, Augusta University, Augusta, Georgia 30912, United States
| | - Wan Jin Jahng
- Department
of Petroleum Chemistry, American University
of Nigeria, Yola 640101, Nigeria
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Tran DT, Pottekat A, Mir SA, Loguercio S, Jang I, Campos AR, Scully KM, Lahmy R, Liu M, Arvan P, Balch WE, Kaufman RJ, Itkin-Ansari P. Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role for Peroxiredoxin 4 in Proinsulin Folding. Diabetes 2020; 69:1723-1734. [PMID: 32457219 PMCID: PMC7372081 DOI: 10.2337/db20-0245] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 05/15/2020] [Indexed: 12/12/2022]
Abstract
The β-cell protein synthetic machinery is dedicated to the production of mature insulin, which requires the proper folding and trafficking of its precursor, proinsulin. The complete network of proteins that mediate proinsulin folding and advancement through the secretory pathway, however, remains poorly defined. Here we used affinity purification and mass spectrometry to identify, for the first time, the proinsulin biosynthetic interaction network in human islets. Stringent analysis established a central node of proinsulin interactions with endoplasmic reticulum (ER) folding factors, including chaperones and oxidoreductases, that is remarkably conserved in both sexes and across three ethnicities. The ER-localized peroxiredoxin PRDX4 was identified as a prominent proinsulin-interacting protein. In β-cells, gene silencing of PRDX4 rendered proinsulin susceptible to misfolding, particularly in response to oxidative stress, while exogenous PRDX4 improved proinsulin folding. Moreover, proinsulin misfolding induced by oxidative stress or high glucose was accompanied by sulfonylation of PRDX4, a modification known to inactivate peroxiredoxins. Notably, islets from patients with type 2 diabetes (T2D) exhibited significantly higher levels of sulfonylated PRDX4 than islets from healthy individuals. In conclusion, we have generated the first reference map of the human proinsulin interactome to identify critical factors controlling insulin biosynthesis, β-cell function, and T2D.
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Affiliation(s)
- Duc T Tran
- Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
| | - Anita Pottekat
- Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
| | - Saiful A Mir
- Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
| | | | - Insook Jang
- Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
| | | | - Kathleen M Scully
- Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
| | - Reyhaneh Lahmy
- Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
| | - Ming Liu
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI
- Department of Endocrinology and Metabolism, Tianjin Medical University, Tianjin, China
| | - Peter Arvan
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI
| | - William E Balch
- Department of Molecular Medicine, Scripps Research, La Jolla, CA
- Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA
| | - Randal J Kaufman
- Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
| | - Pamela Itkin-Ansari
- Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
- Department of Pediatrics, University of California, San Diego, La Jolla, CA
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The Single Administration of a Chromophore Alleviates Neural Defects in Diabetic Retinopathy. THE AMERICAN JOURNAL OF PATHOLOGY 2020; 190:1505-1512. [PMID: 32275905 DOI: 10.1016/j.ajpath.2020.03.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 03/04/2020] [Accepted: 03/24/2020] [Indexed: 12/20/2022]
Abstract
Diabetic retinopathy (DR) is a common complication of diabetes and a leading cause of blindness among the working-age population. Diabetic patients often experience functional deficits in dark adaptation, contrast sensitivity, and color perception before any microvascular pathologies on the fundus become detectable. Previous studies showed that the regeneration of 11-cis-retinal and visual pigment is impaired in a type 1 diabetes animal model, which negatively affects visual function at the early stage of DR. Here, Akita mice, type 1 diabetic model, were treated with the visual pigment chromophore, 9-cis-retinal. This treatment rescued a- and b-wave amplitudes of scotopic electroretinography responses, compared with vehicle-treated Akita mice. In addition, the administration of 9-cis-retinal alleviated oxidative stress significantly as shown by reduced 3-nitrotyrosine levels in the retina of Akita mice. Furthermore, the 9-cis-retinal treatment decreased retinal apoptosis as shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and DNA fragment enzyme-linked immunosorbent assay. Overall, these findings showed that 9-cis-retinal administration restored visual pigment formation and decreased oxidative stress and retinal degeneration, which resulted in improved visual function in diabetic mice, suggesting that chromophore deficiency plays a causative role in visual defects in early DR.
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del Olmo García MI, Merino-Torres JF. GLP 1 receptor agonists, glycemic variability, oxidative stress and acute coronary syndrome. Med Hypotheses 2020; 136:109504. [PMID: 31794876 DOI: 10.1016/j.mehy.2019.109504] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 11/08/2019] [Accepted: 11/16/2019] [Indexed: 01/05/2023]
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Incorporating of gold nanoclusters into metal-organic frameworks for highly sensitive detection of 3-nitrotyrosine as an oxidative stress biomarker. J Photochem Photobiol A Chem 2020. [DOI: 10.1016/j.jphotochem.2020.112370] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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31
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Azemi AK, Mokhtar SS, Rasool AHG. Clinacanthus nutans: Its potential against diabetic vascular diseases. BRAZ J PHARM SCI 2020. [DOI: 10.1590/s2175-97902020000118838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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32
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Dimova R, Chakarova N, Grozeva G, Kirilov G, Tankova T. The relationship between glucose variability and insulin sensitivity and oxidative stress in subjects with prediabetes. Diabetes Res Clin Pract 2019; 158:107911. [PMID: 31707004 DOI: 10.1016/j.diabres.2019.107911] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 10/13/2019] [Accepted: 10/28/2019] [Indexed: 12/21/2022]
Abstract
AIM The present study assessed the relationship between glucose variability (GV) and insulin levels, insulin resistance and oxidative stress at early stages of glucose intolerance. MATERIAL AND METHODS A total of 50 subjects - 12 males and 38 females, mean age 55.6 ± 9.7 years, mean BMI 28.4 ± 6.4 kg/m2, divided into 2 groups according to glucose tolerance: 32 with prediabetes and 18 with normal glucose tolerance were included. Glucose tolerance was assessed by OGTT according to WHO 2006 criteria. Plasma glucose and serum insulin were measured at fasting, 120-minute and 180-minute during the test; and oxLDL and 3-Nitrotyrosine - at fasting and 120-minute. HOMA-IR and OGIS indexes were calculated. HbA1c and lipid levels was assessed. Continuous glucose monitoring was performed with a blind sensor (FreeStyle Libre Pro) for a mean period of 13.6 ± 2.3 days. RESULTS Our results demonstrate significantly increased insulin resistance in subjects with prediabetes, whereas there is no difference in oxidative stress markers between the two groups. OxLDL and 3-NT correlate positively with insulin levels and HOMA-IR and negatively with OGIS in both groups. There is a positive association between oxidative stress markers and 120-minute glucose in the prediabetes group. Insulin levels and HOMA-IR are positively related to plasma glucose and reciprocally to CV and M-Value in prediabetes, since the latter association is with borderline significance after adjustment for hypertension and smoking. CONCLUSIONS Our results demonstrate a significant correlation between oxidative stress and insulin resistance at early stages of glucose intolerance. Both chronic hyperglycemia and GV seem to be related to insulin levels and insulin resistance, and just postload glycaemia to oxidative stress in prediabetes.
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Affiliation(s)
- Rumyana Dimova
- Department of Endocrinology, Medical University - Sofia, Bulgaria.
| | - Nevena Chakarova
- Department of Endocrinology, Medical University - Sofia, Bulgaria
| | - Greta Grozeva
- Department of Endocrinology, Medical University - Sofia, Bulgaria
| | - Georgi Kirilov
- Department of Endocrinology, Medical University - Sofia, Bulgaria
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Roudsari NM, Lashgari NA, Momtaz S, Farzaei MH, Marques AM, Abdolghaffari AH. Natural polyphenols for the prevention of irritable bowel syndrome: molecular mechanisms and targets; a comprehensive review. Daru 2019; 27:755-780. [PMID: 31273572 PMCID: PMC6895345 DOI: 10.1007/s40199-019-00284-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 06/14/2019] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a well diagnosed disease, thoroughly attributed to series of symptoms criteria that embrace a broad range of abdominal complainers. Such criteria help to diagnosis the disease and can guide controlled clinical trials to seek new therapeutic agents. Accordingly, a verity of mechanisms and pathophysiological conditions including inflammation, oxidative stress, lipid peroxidation and different life styles are involved in IBS. Predictably, diverse therapeutic approaches are available and prescribed by clinicians due to major manifestations (i.e., diarrhea-predominance, constipation-predominance, abdominal pain and visceral hypersensitivity), psychological disturbances, and patient preferences between herbal treatments versus pharmacological therapies, dietary or microbiological approaches. Herein, we gathered the latest scientific data between 1973 and 2019 from databases such as PubMed, Google Scholar, Scopus and Cochrane library on relevant studies concerning beneficial effects of herbal treatments for IBS, in particular polyphenols. This is concluded that polyphenols might be applicable for preventing IBS and improving the IBS symptoms, mainly through suppressing the inflammatory signaling pathways, which nowadays are known as novel platform for the IBS management. Graphical abstract.
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Affiliation(s)
- Nazanin Momeni Roudsari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Naser-Aldin Lashgari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - André M Marques
- Oswaldo Cruz Foundation (FIOCRUZ), Institute of Technology in Pharmaceuticals (Farmanguinhos), Rio de Janeiro, RJ, Brazil
| | - Amir Hossein Abdolghaffari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
- Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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Abstract
OBJECTIVES The current laboratory study quantified blood oxidative stress to woodsmoke exposure. METHODS Participants inhaled woodsmoke during three randomized crossover exercise trials (Clean Air [0 μg/m], Low Exposure [250 μg/m], and High Exposure [500 μg/m], Woodsmoke [particulate matter less than 2.5 μm, PM2.5]). Trolox equivalent antioxidant capacity (TEAC), uric acid (UA), 8-isoprostanes (8-ISO), lipid hydroperoxides (LOOH), protein carbonyls (PC), nitrotyrosine (3-NT), 8-isoprostane, and myeloperoxidase (MPO) were quantified in Pre, immediately Post, and 1- (1Hr) hour post blood samples. RESULTS UA decreased following Low Exposure, while plasma TEAC levels increased Post and 1Hr. LOOH levels decreased 1Hr Post (High Exposure), while 8-Iso increased following both smoke trials. PC and MPO were unchanged following all trials, while 3-NT increased over Clean Air. CONCLUSION Blood oxidative stress occurred largely independent of PM2.5 concentrations. Future studies should employ longer duration smoke and exercise combined with physiologic parameters.
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35
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Tang L, Fang C. Nitration of Tyrosine Channels Photoenergy through a Conical Intersection in Water. J Phys Chem B 2019; 123:4915-4928. [PMID: 31094198 DOI: 10.1021/acs.jpcb.9b03464] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Nitration of tyrosine occurs under oxidative stress in vivo. The product, 3-nitrotyrosine (3NY), has a dramatically decreased quantum yield and can be used as a molecular ruler. In this study, femtosecond transient absorption spectroscopy and quantum calculations were implemented to elucidate the photoinduced relaxation processes of anionic 3NY in water. Upon 400 nm excitation into an excited electronic state with notable charge-transfer (CT) character, a barrierless nitro-twisting motion rapidly (<100 fs) guides the chromophore into an adjacent twisted intramolecular CT state, therein reaching a sloped S1/S0 conical intersection on the ∼100 fs time scale. Once in the hot ground state, excess energy is further released through vibrational cooling with biexponential time constants of ∼140 and 680 fs in water. Nitro back-twisting occurs on longer time scales (∼1.1 and 9 ps in water), returning the system to original ground state. Systematic evaluations of excited-state potential energies of anionic 3NY were performed by density functional theory (DFT) and time-dependent DFT calculations, showing that intersystem crossing (ISC) from the first singlet state (S1) to the first or second triplet state (T1 or T2) is unlikely. Inclusion of an explicit water molecule in calculations leads to improved mapping of the excited-state energy ordering of the second singlet state (S2) and T2, further diminishing ISC probability from S1 and favoring an ultrafast internal conversion to S0. These results provide deep insights into the highly efficient nonradiative decay of anionic 3NY in aqueous solution, with nitro-site-specific information that can help infer the characterization and potential optogenetic control of 3NY in protein environment.
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Affiliation(s)
- Longteng Tang
- Department of Chemistry , Oregon State University , 153 Gilbert Hall , Corvallis , Oregon 97331-4003 , United States
| | - Chong Fang
- Department of Chemistry , Oregon State University , 153 Gilbert Hall , Corvallis , Oregon 97331-4003 , United States
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Age-Dependent Oxidative Stress Elevates Arginase 1 and Uncoupled Nitric Oxide Synthesis in Skeletal Muscle of Aged Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:1704650. [PMID: 31205583 PMCID: PMC6530149 DOI: 10.1155/2019/1704650] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/04/2019] [Indexed: 12/21/2022]
Abstract
Aging is associated with reduced muscle mass (sarcopenia) and poor bone quality (osteoporosis), which together increase the incidence of falls and bone fractures. It is widely appreciated that aging triggers systemic oxidative stress, which can impair myoblast cell survival and differentiation. We previously reported that arginase plays an important role in oxidative stress-dependent bone loss. We hypothesized that arginase activity is dysregulated with aging in muscles and may be involved in muscle pathophysiology. To investigate this, we analyzed arginase activity and its expression in skeletal muscles of young and aged mice. We found that arginase activity and arginase 1 expression were significantly elevated in aged muscles. We also demonstrated that SOD2, GPx1, and NOX2 increased with age in skeletal muscle. Most importantly, we also demonstrated elevated levels of peroxynitrite formation and uncoupling of eNOS in aged muscles. Our in vitro studies using C2C12 myoblasts showed that the oxidative stress treatment increased arginase activity, decreased cell survival, and increased apoptotic markers. These effects were reversed by treatment with an arginase inhibitor, 2(S)-amino-6-boronohexanoic acid (ABH). Our study provides strong evidence that L-arginine metabolism is altered in aged muscle and that arginase inhibition could be used as a novel therapeutic target for age-related muscle complications.
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Ali MY, Zaib S, Rahman MM, Jannat S, Iqbal J, Park SK, Chang MS. Didymin, a dietary citrus flavonoid exhibits anti-diabetic complications and promotes glucose uptake through the activation of PI3K/Akt signaling pathway in insulin-resistant HepG2 cells. Chem Biol Interact 2019; 305:180-194. [PMID: 30928401 DOI: 10.1016/j.cbi.2019.03.018] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 03/12/2019] [Accepted: 03/21/2019] [Indexed: 02/06/2023]
Abstract
Didymin is a naturally occurring orally active flavonoid glycoside (isosakuranetin 7-O-rutinoside) found in various citrus fruits, which has been previously reported to possess a wide variety of pharmacological activities including anticancer, antioxidant, antinociceptive, neuroprotective, hepatoprotective, inflammatory, and cardiovascular. However, there have not been any reports concerning its anti-diabetic potential until now. Therefore, we evaluated the anti-diabetic potential of didymin via inhibition of α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), rat lens aldose reductase (RLAR), human recombinant AR (HRAR), and advanced glycation end-product (AGE) formation inhibitory assays. Didymin strongly inhibited PTP1B, α-glucosidase, HRAR, RLAR, and AGE in the corresponding assays. Kinetic study revealed that didymin exhibited a mixed type inhibition against α-glucosidase and HRAR, while it competitively inhibited PTP1B and RLAR. Docking simulations of didymin demonstrated negative binding energies and close proximity to residues in the binding pocket of HRAR, RLAR, PTP1B and α-glucosidase, indicating that didymin have high affinity and tight binding capacity towards the active site of these enzymes. Furthermore, we also examined the molecular mechanisms underlying the anti-diabetic effects of didymin in insulin-resistant HepG2 cells which significantly increased glucose uptake and decreased the expression of PTP1B in insulin-resistant HepG2 cells. In addition, didymin activated insulin receptor substrate (IRS)-1 by increasing phosphorylation at tyrosine 895 and enhanced the phosphorylations of phosphoinositide 3-kinase (PI3K), Akt, and glycogen synthasekinase-3(GSK-3). Interestingly, didymin reduced the expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, two key enzymes involved in the gluconeogenesis and leading to a diminished glucose production. The results of the present study clearly demonstrated that didymin will be useful for developing multiple target-oriented therapeutic modalities for treatment of diabetes, and diabetes-associated complications.
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Affiliation(s)
- Md Yousof Ali
- Department of Chemistry and Biochemistry, Faculty of Arts and Science, Concordia University, 7141 Sherbrooke St. W., Montreal, Quebec, Canada; Department of Biology, Faculty of Arts and Science, Concordia University, 7141 Sherbrooke St. W., Montreal, Quebec, Canada; Centre for Structural and Functional Genomic, Dept. of Biology, Faculty of Arts and Science, Concordia University, 7141 Sherbrooke St. W., Montreal, QC, Canada; Department of Prescriptionology, College of Korean Medicine, Kyung Hee University, 26, Kyunghee Dae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
| | - Sumera Zaib
- Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan
| | - M Mizanur Rahman
- Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia, 7003, Bangladesh
| | - Susoma Jannat
- Department of Biochemistry and Molecular Biology, College of Medicine, Korea Molecular Medicine and Nutrition Research Institute, Korea University, Seoul, 02841, Republic of Korea
| | - Jamshed Iqbal
- Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan
| | - Seong Kyu Park
- Department of Prescriptionology, College of Korean Medicine, Kyung Hee University, 26, Kyunghee Dae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea
| | - Mun Seog Chang
- Department of Prescriptionology, College of Korean Medicine, Kyung Hee University, 26, Kyunghee Dae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea
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Zhao J, Wu J, Yang Z, Ouyang L, Zhu L, Gao Z, Li H. Nitration of hIAPP promotes its toxic oligomer formation and exacerbates its toxicity towards INS-1 cells. Nitric Oxide 2019; 87:23-30. [PMID: 30849493 DOI: 10.1016/j.niox.2019.02.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 02/27/2019] [Accepted: 02/28/2019] [Indexed: 01/09/2023]
Abstract
Amyloid formation of human islet amyloid polypeptide (hIAPP) is one of the most common pathological features of type 2 diabetes (T2D). Increasing evidences have shown that the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an important role in the development of the T2D. Interestingly, our previous studies indicated that heme could bind to hIAPP, and the complex might induce the nitration of tyrosine residue (Y37) of hIAPP in the presence of hydrogen peroxide and nitrite. However, it remains unclear about effect of the nitration on the implicated function of hIAPP in the development of T2D. In this study, fluorescent assays, transmission electron microscopy (TEM), atomic force microscope (AFM) were used to demonstrate that nitration of hIAPP significantly decreased its fibril formation. But the decreased fibril formation was not through the diminished aggregation of hIAPP monomer as suggested by the results of circular dichroism spectroscopy (CD) and gel electrophoresis assay. Surface-enhanced raman spectroscopy (SERS) indicated that nitration of hIAPP impaired the intermolecular hydrogen bonding. On the basis of these results, we hypothesize that nitration of hIAPP may block the intermolecular hydrogen bonding, leading to the inhibition of its fibril formation. In addition, cytotoxicity study of native and modified hIAPP was also performed on INS-1 cells, which revealed exacerbated toxicity of hIAPP by its nitration. The findings in this study that nitration of hIAPP promotes its oligomer formation and thus exacerbates its cytotoxicity suggests a possible link between the nitrite (or the sum of nitrite and nitrate) levels and T2D, and ameliorated nitration of hIAPP by diminishing nitrative stress might be a promising therapeutic strategy for T2D.
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Affiliation(s)
- Jie Zhao
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China
| | - Jinming Wu
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China
| | - Zhen Yang
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China; Center for Bioenergetics, Houston Methodist Research Institute, Houston, TX, 77030, United States
| | - Lei Ouyang
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China
| | - Lihua Zhu
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China
| | - Zhonghong Gao
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
| | - Hailing Li
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
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Abstract
Current kidney-on-chip models lack the 3D geometry, complexity, and functionality vital for recapitulating in vivo renal tissue. We report the fabrication and perfusion of 3D vascularized proximal tubules embedded within an engineered ECM that exhibit active reabsorption of solutes via tubular–vascular exchange. Using this model, we quantified albumin and glucose reabsorption over time. We also studied hyperglycemic effects in the absence and presence of a glucose transport inhibitor. Our 3D kidney tissue provides a platform for in vitro studies of kidney function, disease modeling, and pharmacology. Three-dimensional renal tissues that emulate the cellular composition, geometry, and function of native kidney tissue would enable fundamental studies of filtration and reabsorption. Here, we have created 3D vascularized proximal tubule models composed of adjacent conduits that are lined with confluent epithelium and endothelium, embedded in a permeable ECM, and independently addressed using a closed-loop perfusion system to investigate renal reabsorption. Our 3D kidney tissue allows for coculture of proximal tubule epithelium and vascular endothelium that exhibits active reabsorption via tubular–vascular exchange of solutes akin to native kidney tissue. Using this model, both albumin uptake and glucose reabsorption are quantified as a function of time. Epithelium–endothelium cross-talk is further studied by exposing proximal tubule cells to hyperglycemic conditions and monitoring endothelial cell dysfunction. This diseased state can be rescued by administering a glucose transport inhibitor. Our 3D kidney tissue provides a platform for in vitro studies of kidney function, disease modeling, and pharmacology.
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Aggarwal H, Kanuri BN, Dikshit M. Role of iNOS in Insulin Resistance and Endothelial Dysfunction. OXIDATIVE STRESS IN HEART DISEASES 2019:461-482. [DOI: 10.1007/978-981-13-8273-4_21] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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He Q, Chen Y, Shen D, Cui X, Zhang C, Yang H, Zhong W, Eremin SA, Fang Y, Zhao S. Development of a surface plasmon resonance immunosensor and ELISA for 3-nitrotyrosine in human urine. Talanta 2018; 195:655-661. [PMID: 30625597 DOI: 10.1016/j.talanta.2018.11.110] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 11/21/2018] [Accepted: 11/29/2018] [Indexed: 12/20/2022]
Abstract
3-Nitrotyrosine (3-NT) is thought to be a relevant biomarker of nitrosative stress which is associated with many inflammatory and chronic diseases. It is necessary to develop confidential method for specific and sensitive 3-NT detection. In this paper, on the basis of anti-3-NT specific antibody, we developed a label-free indirect competitive surface plasmon resonance (SPR) immunosensor and ELISA for the detection of 3-NT. Under the optimized conditions, the SPR immunosensor can obtain a linear range of 0.17-6.07 μg/mL and a limit of detection (LOD) of 0.12 μg/mL while the ELISA can reach 0.33-9.94 μg/mL and a LOD of 0.24 μg/mL.The selectivity of 3-NT was also testified by six kinds of amino acid analogues. Besides, the developed SPR immunosensor was compared thoroughly with a conventional ELISA in spiked analysis of urine samples. Good recoveries and correlation between these two methods were observed (R2 = 0.964). Therefore, it is concluded that the automated SPR platform can be applied to quantify 3-NT in biological samples with its sensitivity, accuracy, and real-timing.
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Affiliation(s)
- Qiyi He
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Yingshan Chen
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Ding Shen
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Xiping Cui
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Chunguo Zhang
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Huiyi Yang
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Wenying Zhong
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Sergei A Eremin
- Faculty of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia; National Research Technical University MISiS, 119049 Moscow, Russia.
| | - Yanxiong Fang
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Suqing Zhao
- Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
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Han X, Wang Z, Wang J, Li Y, Hu H, Hu Y, Zhao X, Zhan Y, Yuan J, Wei S, Liang Y, Zhang X, Guo H, Yang H, Wu T, Kong W, He M. Metabolic syndrome is associated with hearing loss among a middle-aged and older Chinese population: a cross-sectional study. Ann Med 2018; 50:587-595. [PMID: 29693425 DOI: 10.1080/07853890.2018.1469786] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Abstract
BACKGROUND Although the association of metabolic syndrome (MetS) and hearing loss has been evaluated, findings are controversial. This study investigated this association in a Chinese population. METHODS A cross-sectional study including a total of 18,824 middle-aged and older participants from the Dongfeng-Tongji Cohort study was conducted. Hearing loss was defined as the pure-tone average (PTA) of frequencies 0.5, 1.0, 2.0, and 4.0 kHz >25 decibels hearing level (dB HL) in the better ear and graded as mild (PTA 26-40 dB HL), moderate (PTA >40 to ≤60 dB HL), and severe (PTA >60 dB HL). MetS was defined according to the International Diabetes Foundation (IDF) criteria of 2005. Association analysis was performed by logistic regression. RESULTS After adjustment for potential confounders, participants with MetS showed higher OR of hearing loss (OR, 1.11; 95% CI: 1.03-1.19). The MetS components including central obesity (OR, 1.07; 95% CI: 1.01-1.15) and hyperglycemia (OR, 1.12; 95% CI: 1.04-1.20) were also positively associated with hearing loss. Low HDL-C levels were also associated with higher OR of moderate/severe hearing loss (OR, 1.21; 95% CI: 1.07-1.36). CONCLUSIONS The MetS, including its components central obesity, hyperglycemia, and low HDL-C levels were positively associated with hearing loss. Key messages Studies indicated that cardiovascular disease and diabetes might be risk factors of hearing loss. However, few efforts have been made to establish a direct relationship between metabolic syndrome and hearing loss, especially in Chinese population. In the present study, a cross-sectional design using data from the Dongfeng-Tongji Cohort study was conducted to assess the association between metabolic syndrome and hearing loss. The metabolic syndrome, as well as its components central obesity, hyperglycemia, and low HDL-C levels were positively associated with hearing loss.
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Affiliation(s)
- Xu Han
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Zhichao Wang
- b Department of Otorhinolaryngology , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Jing Wang
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Yaru Li
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Hua Hu
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Yujuan Hu
- b Department of Otorhinolaryngology , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Xueyan Zhao
- b Department of Otorhinolaryngology , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Yue Zhan
- b Department of Otorhinolaryngology , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Jing Yuan
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Sheng Wei
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Yuan Liang
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Xiaomin Zhang
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Huan Guo
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Handong Yang
- c Dongfeng Central Hospital , Dongfeng Motor Corporation and Hubei University of Medicine , Shiyan , Hubei , China
| | - Tangchun Wu
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
| | - Weijia Kong
- b Department of Otorhinolaryngology , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Meian He
- a Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health , School of Public Health, Huazhong University of Science and Technology , Wuhan , China
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Zhai L, Wang X. Syringaresinol‑di‑O‑β‑D‑glucoside, a phenolic compound from Polygonatum sibiricum, exhibits an antidiabetic and antioxidative effect on a streptozotocin‑induced mouse model of diabetes. Mol Med Rep 2018; 18:5511-5519. [PMID: 30365054 PMCID: PMC6236259 DOI: 10.3892/mmr.2018.9580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 03/22/2018] [Indexed: 11/26/2022] Open
Abstract
Syringaresinol-di-O-β-D-glucoside (SOG) is a phenolic compound extracted from Polygonatum sibiricum. The present study aimed to investigate the antidiabetic effect of SOG on streptozocin (STZ)-induced diabetic mice and determine the potential underlying mechanisms. In the present study, fasting blood glucose and organ indexes of mice were analyzed. Body weight, water intake and food intake were also recorded. Furthermore, serum fasting insulin, pancreatic insulin and pancreatic interleukin-6 levels of mice were determined using ELISA kits to investigate the effect of SOG on the levels of insulin. Levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and free fatty acid (FFA) in the serum of mice, and levels of TC, TG and total protein in the kidney, were also determined to investigate the effects of SOG on lipid and protein metabolism in mice. Furthermore, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) levels, as well as total antioxidant capacity (T-AOC), in the kidneys of mice were determined to investigate the effect of SOG on oxidative stress. Western blotting was also performed to determine the expression of proteins associated with oxidative stress. The results demonstrated that SOG (25, 50 and 75 mg/kg) induced a significant antidiabetic effect in mice. Treatment with SOG promoted insulin secretion and decreased TC, TG, LDL-C, VLDL-C, FFA, MDA, SOD, CAT, AST, ALT and ALP levels in the kidneys of mice, as well as kidney TC and TG levels, but increased the levels of kidney total protein and the T-AOC in kidneys. Furthermore, SOG treatment could significantly downregulate the expressions of nitrotyrosine and transforming growth factor-β1 in diabetic mice. Therefore, the present study indicated that SOG may exert an antidiabetic effect on STZ-induced diabetic mice and that the mechanism of SOG may be associated with its antioxidative activity.
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Affiliation(s)
- Liping Zhai
- Department of Endocrinology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Xu Wang
- Department of Endocrinology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
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44
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Affiliation(s)
- Yan Gao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China
| | - Kit Ieng Kuok
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China
| | - Ying Jin
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China
| | - Ruibing Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China
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Supplementation with l -glutathione improves oxidative status and reduces protein nitration in myenteric neurons in the jejunum in diabetic Rattus norvegicus. Exp Mol Pathol 2018; 104:227-234. [DOI: 10.1016/j.yexmp.2018.05.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 04/23/2018] [Accepted: 05/10/2018] [Indexed: 12/29/2022]
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Knight AR, Taylor EL, Lukaszewski R, Jensen KT, Jones HE, Carré JE, Isupov MN, Littlechild JA, Bailey SJ, Brewer E, McDonald TJ, Pitt AR, Spickett CM, Winyard PG. A high-sensitivity electrochemiluminescence-based ELISA for the measurement of the oxidative stress biomarker, 3-nitrotyrosine, in human blood serum and cells. Free Radic Biol Med 2018; 120:246-254. [PMID: 29555590 DOI: 10.1016/j.freeradbiomed.2018.03.026] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 03/13/2018] [Accepted: 03/14/2018] [Indexed: 02/02/2023]
Abstract
The generation of 3-nitrotyrosine, within proteins, is a post-translational modification resulting from oxidative or nitrative stress. It has been suggested that this modification could be used as a biomarker for inflammatory diseases. Despite the superiority of mass spectrometry-based determinations of nitrotyrosine, in a high-throughput clinical setting the measurement of nitrotyrosine by an enzyme-linked immunosorbent assay (ELISA) is likely to be more cost-effective. ELISAs offer an alternative means to detect nitrotyrosine, but many commercially available ELISAs are insufficiently sensitive to detect nitrotyrosine in healthy human serum. Here, we report the development, validation and clinical application of a novel electrochemiluminescence-based ELISA for nitrotyrosine which provides superior sensitivity (e.g. a 50-fold increase in sensitivity compared with one of the tested commercial colorimetric ELISAs). This nitrotyrosine ELISA has the following characteristics: a lower limit of quantitation of 0.04 nM nitrated albumin equivalents; intra- and inter-assay coefficients of variation of 6.5% and 11.3%, respectively; a mean recovery of 106 ± 3% and a mean linearity of 0.998 ± 0.001. Far higher nitration levels were measured in normal human blood cell populations when compared to plasma. Mass spectrometry was used to validate the new ELISA method. The analysis of the same set of chemically modified albumin samples using the ELISA method and mass spectrometry showed good agreement for the relative levels of nitration present in each sample. The assay was applied to serum samples from patients undergoing elective surgery which induces the human inflammatory response. Matched samples were collected before and one day after surgery. An increase in nitration was detected following surgery (median (IQR): 0.59 (0.00-1.34) and 0.97 (0.00-1.70) nitrotyrosine (fmol of nitrated albumin equivalents/mg protein) for pre- and post-surgery respectively. The reported assay is suitable for nitrotyrosine determination in patient serum samples, and may also be applicable as a means to determine oxidative stress in primary and cultured cell populations.
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Affiliation(s)
- Annie R Knight
- University of Exeter Medical School, St Luke's Campus, Magdalen Road, Exeter EX1 2LU, UK
| | - Emma L Taylor
- University of Exeter Medical School, St Luke's Campus, Magdalen Road, Exeter EX1 2LU, UK
| | | | - Karina Tveen Jensen
- School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
| | - Helen E Jones
- CBR Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK
| | - Jane E Carré
- University of Exeter Medical School, St Luke's Campus, Magdalen Road, Exeter EX1 2LU, UK
| | - Michail N Isupov
- Henry Wellcome Building for Biocatalysis, Biosciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK
| | - Jennifer A Littlechild
- Henry Wellcome Building for Biocatalysis, Biosciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK
| | - Stephen J Bailey
- Sport and Health Sciences, Richards Building, University of Exeter, St Luke's Campus, Magdalen Road, Exeter EX1 2LU, UK
| | - Emily Brewer
- Clinical Chemistry, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter EX2 5DW, UK
| | - Timothy J McDonald
- Clinical Chemistry, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter EX2 5DW, UK
| | - Andrew R Pitt
- School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
| | - Corinne M Spickett
- School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
| | - Paul G Winyard
- University of Exeter Medical School, St Luke's Campus, Magdalen Road, Exeter EX1 2LU, UK.
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Elshaer SL, Lemtalsi T, El-Remessy AB. High Glucose-Mediated Tyrosine Nitration of PI3-Kinase: A Molecular Switch of Survival and Apoptosis in Endothelial Cells. Antioxidants (Basel) 2018; 7:antiox7040047. [PMID: 29587384 PMCID: PMC5946113 DOI: 10.3390/antiox7040047] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 03/19/2018] [Accepted: 03/21/2018] [Indexed: 12/31/2022] Open
Abstract
Diabetes and hyperglycemia are associated with increased retinal oxidative and nitrative stress and vascular cell death. Paradoxically, high glucose stimulates expression of survival and angiogenic growth factors. Therefore, we examined the hypothesis that high glucose-mediated tyrosine nitration causes inhibition of the survival protein PI3-kinase, and in particular, its regulatory p85 subunit in retinal endothelial cell (EC) cultures. Retinal EC were cultured in high glucose (HG, 25 mM) for 3 days or peroxynitrite (PN, 100 µM) overnight in the presence or absence of a peroxynitrite decomposition catalyst (FeTPPs, 2.5 µM), or the selective nitration inhibitor epicatechin (100 µM). Apoptosis of ECs was assessed using TUNEL assay and caspase-3 activity. Immunoprecipitation and Western blot were used to assess protein expression and tyrosine nitration of p85 subunit and its interaction with the p110 subunit. HG or PN accelerated apoptosis of retinal ECs compared to normal glucose (NG, 5 mM) controls. HG- or PN-treated cells also showed significant increases in tyrosine nitration on the p85 subunit of PI3-kinase that inhibited its association with the catalytic p110 subunit and impaired PI3-kinase/Akt kinase activity. Decomposing peroxynitrite or blocking tyrosine nitration of p85 restored the activity of PI3-kinase, and prevented apoptosis and activation of p38 MAPK. Inhibiting p38 MAPK or overexpression of the constitutively activated Myr-Akt construct prevented HG- or peroxynitrite-mediated apoptosis. In conclusion, HG impairs pro-survival signals and causes accelerated EC apoptosis, at least in part via tyrosine nitration and inhibition of PI3-kinase. Inhibitors of nitration can be used in adjuvant therapy to delay diabetic retinopathy and microvascular complication.
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Affiliation(s)
- Sally L Elshaer
- Retinopathy Research, Augusta Biomedical Research Corporation Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
| | - Tahira Lemtalsi
- Retinopathy Research, Augusta Biomedical Research Corporation Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
| | - Azza B El-Remessy
- Retinopathy Research, Augusta Biomedical Research Corporation Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
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Tavares RS, Escada-Rebelo S, Silva AF, Sousa MI, Ramalho-Santos J, Amaral S. Antidiabetic therapies and male reproductive function: where do we stand? Reproduction 2018; 155:R13-R37. [DOI: 10.1530/rep-17-0390] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 09/15/2017] [Accepted: 10/09/2017] [Indexed: 12/21/2022]
Abstract
Diabetes mellitus has been increasing at alarming rates in recent years, thus jeopardizing human health worldwide. Several antidiabetic drugs have been introduced in the market to manage glycemic levels, and proven effective in avoiding, minimizing or preventing the appearance or development of diabetes mellitus-related complications. However, and despite the established association between such pathology and male reproductive dysfunction, the influence of these therapeutic interventions on such topics have been scarcely explored. Importantly, this pathology may contribute toward the global decline in male fertility, giving the increasing preponderance of diabetes mellitus in young men at their reproductive age. Therefore, it is mandatory that the reproductive health of diabetic individuals is maintained during the antidiabetic treatment. With this in mind, we have gathered the available information and made a critical analysis regarding the effects of several antidiabetic drugs on male reproductive function. Unlike insulin, which has a clear and fundamental role on male reproductive function, the other antidiabetic therapies' effects at this level seem incoherent. In fact, studies are highly controversial possibly due to the different experimental study approaches, which, in our opinion, suggests caution when it comes to prescribing such drugs to young diabetic patients. Overall, much is still to be determined and further studies are needed to clarify the safety of these antidiabetic strategies on male reproductive system. Aspects such as the effects of insulin levels variations, consequent of insulin therapy, as well as what will be the impact of the side effect hypoglycemia, common to several therapeutic strategies discussed, on the male reproductive system are still to be addressed.
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Qian Y, Chen X, Qi J, Liu X. A novel analytical method based on HPLC-PDA coupled post-column derivatization to evaluate the ability to inhibit tyrosine nitration in lotus leaf extracts. RSC Adv 2018; 8:38715-38720. [PMID: 35558301 PMCID: PMC9090667 DOI: 10.1039/c8ra07087c] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 10/23/2018] [Indexed: 01/16/2023] Open
Abstract
Protein tyrosine nitration plays a key role in many inflammatory and cardiovascular diseases and diabetes. Many natural products are used to treat these diseases through their ability to potentially interfere this reaction. Here, we describe a novel method to provide active fingerprinting of inhibition of tyrosine nitration by natural products based on post-column tyrosine nitration reaction analysis using high-performance liquid chromatography coupled to a photometric diode array. Results indicated that lotus leaf extracts exhibited obvious inhibitory activity against tyrosine nitration by peroxynitrite, and that chemical and active fingerprints were simultaneously established, with the active fingerprints indicating the active compounds of the lotus leaves. Additionally, flavonoids were screened as the principal active compounds involved in inhibiting tyrosine nitration in the lotus leaf extracts, with quercetin-3-O-glucuronide and quercetin-3-O-glucoside exhibiting the greatest contributions. Moreover, our results suggested that lotus leaves from three regions (Nanjing, Suzhou, and Hangzhou) exhibited the best inhibitory activity. These findings indicated the usefulness of this method for screening active compounds involved in inhibiting protein tyrosine nitration, and that similar strategies can likely be applied to evaluate the inhibitory activity against tyrosine nitration of other natural products. A novel analytical method based on HPLC-PDA coupled post-column derivatization to evaluate the inhibitory activity of tyrosine nitration in lotus leaf extracts.![]()
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Affiliation(s)
- Yin Qian
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research
- School of Traditional Chinese Pharmacy
- China Pharmaceutical University
- Nanjing 211198
- PR China
| | - Xi Chen
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research
- School of Traditional Chinese Pharmacy
- China Pharmaceutical University
- Nanjing 211198
- PR China
| | - Jin Qi
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research
- School of Traditional Chinese Pharmacy
- China Pharmaceutical University
- Nanjing 211198
- PR China
| | - Xuming Liu
- School of Life Science and Technology
- China Pharmaceutical University
- Nanjing 211198
- PR China
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Ali MY, Kim DH, Seong SH, Kim HR, Jung HA, Choi JS. α-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitory Activity of Plastoquinones from Marine Brown Alga Sargassum serratifolium. Mar Drugs 2017; 15:E368. [PMID: 29194348 PMCID: PMC5742828 DOI: 10.3390/md15120368] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 11/18/2017] [Accepted: 11/27/2017] [Indexed: 01/22/2023] Open
Abstract
Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-cancer, anti-inflammatory, antioxidant, and neuroprotective activity. This study aims to investigate the anti-diabetic activity of S. serratifolium and its major constituents through inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, and ONOO--mediated albumin nitration. S. serratifolium ethanolic extract and fractions exhibited broad PTP1B and α-glucosidase inhibitory activity (IC50, 1.83~7.04 and 3.16~24.16 µg/mL for PTP1B and α-glucosidase, respectively). In an attempt to identify bioactive compounds, three plastoquinones (sargahydroquinoic acid, sargachromenol and sargaquinoic acid) were isolated from the active n-hexane fraction of S. serratifolium. All three plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the IC50 range of 5.14-14.15 µM, while sargachromenol and sargaquinoic acid showed dose-dependent inhibitory activity against α-glucosidase (IC50 42.41 ± 3.09 and 96.17 ± 3.48 µM, respectively). In the kinetic study of PTP1B enzyme inhibition, sargahydroquinoic acid and sargaquinoic acid led to mixed-type inhibition, whereas sargachromenol displayed noncompetitive-type inhibition. Moreover, plastoquinones dose-dependently inhibited ONOO--mediated albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B and α-glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the prevention and treatment of type 2 diabetes.
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Affiliation(s)
- Md Yousof Ali
- Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
| | - Da Hye Kim
- Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
| | - Su Hui Seong
- Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
| | - Hyeung-Rak Kim
- Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
| | - Hyun Ah Jung
- Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Korea.
| | - Jae Sue Choi
- Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
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