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Wen J, Liu C, Deng C. Research progress on the mechanism of aging of vascular endothelial cells and the intervention of traditional Chinese medicine: A review. Medicine (Baltimore) 2022; 101:e32248. [PMID: 36626478 PMCID: PMC9750530 DOI: 10.1097/md.0000000000032248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Vascular senescence is the basic factor of many cardiovascular diseases. Vascular endothelium, as a protective barrier between blood and vascular wall, plays an important role in maintaining the integrity and homeostasis of vascular system. Endothelial cell senescence is an important pathological change of vascular senescence. In recent years, more and more studies have been conducted on vascular endothelial cell senescence, especially on its mechanism. Many research results showed that the mechanism is various, but the systematic elucidation still lacks. Western medicine has little choice in the prevention and treatment of endothelial cell senescence, and the control effect is also limited, while Chinese medicine makes up for the deficiency in this regard. The main mechanisms of vascular endothelial cell aging and the related research progress of traditional Chinese medicine in the prevention and treatment of vascular endothelial aging in recent years were summarized in this paper to provide reference for the research of traditional Chinese medicine in anti-vascular aging and the prevention and treatment of cardiovascular disease.
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Affiliation(s)
- Jiang Wen
- College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Caixia Liu
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Changqing Deng
- College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
- * Correspondence: Changqing Deng, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China (e-mail: )
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Diwan B, Sharma R. Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review. Food Sci Biotechnol 2022; 31:1089-1109. [PMID: 35756719 PMCID: PMC9206104 DOI: 10.1007/s10068-022-01114-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/27/2022] [Accepted: 06/01/2022] [Indexed: 11/06/2022] Open
Abstract
The process of cellular senescence is rapidly emerging as a modulator of organismal aging and disease. Targeting the development and removal of senescent cells is considered a viable approach to achieving improved organismal healthspan and lifespan. Nutrition and health are intimately linked and an appropriate dietary regimen can greatly impact organismal response to stress and diseases including during aging. With a renewed focus on cellular senescence, emerging studies demonstrate that both primary and secondary nutritional elements such as carbohydrates, proteins, fatty acids, vitamins, minerals, polyphenols, and probiotics can influence multiple aspects of cellular senescence. The present review describes the recent molecular aspects of cellular senescence-mediated understanding of aging and then studies available evidence of the cellular senescence modulatory attributes of major and minor dietary elements. Underlying pathways and future research directions are deliberated to promote a nutrition-centric approach for targeting cellular senescence and thus improving human health and longevity.
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Affiliation(s)
- Bhawna Diwan
- Faculty of Applied Sciences & Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, 173229 India
| | - Rohit Sharma
- Faculty of Applied Sciences & Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, 173229 India
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Jüttner AA, Danser AHJ, Roks AJM. Pharmacological developments in antihypertensive treatment through nitric oxide-cGMP modulation. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2022; 94:57-94. [PMID: 35659377 DOI: 10.1016/bs.apha.2022.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Treatment of hypertension until now has been directed at inhibition of vasoconstriction, of cardiac contractility and of blood volume regulation. Despite the arsenal of drugs available for this purpose, the control of target blood pressure is still a difficult goal to reach in outpatients. The nitric oxide-cyclic guanosine monophosphate signaling is one of the most important mediators of vasodilation. It might therefore be a potential and most welcome drug target for optimization of the treatment of hypertension. In this chapter we review the problems that can occur in this signaling system, the attempts that have been made to correct these problems, and those that are still under investigation. Recently developed, clinically safe medicines that are currently approved for other applications, such as myocardial infarction, await to be tested for essential systemic hypertension. We conclude that despite many years of research without translation, stimulation of nitric oxide-cyclic guanosine monophosphate is still a viable strategy in the prevention of the health risk posed by chronic hypertension.
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Affiliation(s)
- Annika A Jüttner
- Department of Internal Medicine, Division of Vascular Disease and Pharmacology, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands
| | - A H Jan Danser
- Department of Internal Medicine, Division of Vascular Disease and Pharmacology, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands
| | - Anton J M Roks
- Department of Internal Medicine, Division of Vascular Disease and Pharmacology, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands.
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Wu L, Sowers JR, Zhang Y, Ren J. OUP accepted manuscript. Cardiovasc Res 2022; 119:691-709. [PMID: 35576480 DOI: 10.1093/cvr/cvac080] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/21/2022] [Accepted: 04/25/2022] [Indexed: 11/13/2022] Open
Abstract
Cardiovascular diseases (CVDs) arise from a complex interplay among genomic, proteomic, and metabolomic abnormalities. Emerging evidence has recently consolidated the presence of robust DNA damage in a variety of cardiovascular disorders. DNA damage triggers a series of cellular responses termed DNA damage response (DDR) including detection of DNA lesions, cell cycle arrest, DNA repair, cellular senescence, and apoptosis, in all organ systems including hearts and vasculature. Although transient DDR in response to temporary DNA damage can be beneficial for cardiovascular function, persistent activation of DDR promotes the onset and development of CVDs. Moreover, therapeutic interventions that target DNA damage and DDR have the potential to attenuate cardiovascular dysfunction and improve disease outcome. In this review, we will discuss molecular mechanisms of DNA damage and repair in the onset and development of CVDs, and explore how DDR in specific cardiac cell types contributes to CVDs. Moreover, we will highlight the latest advances regarding the potential therapeutic strategies targeting DNA damage signalling in CVDs.
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Affiliation(s)
- Lin Wu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - James R Sowers
- Diabetes and Cardiovascular Research Center, University of Missouri Columbia, Columbia, MO 65212, USA
| | - Yingmei Zhang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Jun Ren
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
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Systematic Pharmacology Reveals the Antioxidative Stress and Anti-Inflammatory Mechanisms of Resveratrol Intervention in Myocardial Ischemia-Reperfusion Injury. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5515396. [PMID: 34093716 PMCID: PMC8163539 DOI: 10.1155/2021/5515396] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 04/10/2021] [Accepted: 04/17/2021] [Indexed: 11/21/2022]
Abstract
Objective To explore the oxidative stress and inflammatory mechanisms of resveratrol intervention in myocardial ischemia-reperfusion injury (MIRI). Methods The potential targets of resveratrol were predicted by PharmMapper. The MIRI genes were collected by Online Mendelian Inheritance in Man (OMIM), GeneCards is used to collect related disease genes, and String is used for enrichment analysis. Animal experiments were then performed to verify the systematic pharmacological results. Hematoxylin-eosin (HE) staining was used to observe myocardial damage. The levels of serum interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in each experimental group were detected. The protein and mRNA expressions of Toll-like receptor 4 (TLR4), nuclear factor-kappa (NF-κB) p65, IL-1β, IL-6, and TNF-α in rat myocardial tissue were measured. Results The results of systematic pharmacology showed that insulin resistance, FoxO signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, PI3K-Akt signaling pathway, ErbB signaling pathway, T-cell receptor signaling pathway, peroxisome proliferator-activated receptors (PPAR) signaling pathway, Ras signaling pathway, TNF signaling pathway, and so on were regulated to improve MIRI. The results of animal experiments showed that the myocardial cells of the sham operation group were arranged in fibrous form, and the myocardial ischemia-reperfusion injury group had obvious cell morphology disorder. Compared with the MIRI group, the resveratrol group had a certain degree of relief. Compared with the MIRI group, serum IL-1β, TNF-α, and IL-6 in the resveratrol group was significantly reduced (P < 0.05), and myocardial tissue TLR4, NF-κB p65, IL-1β, IL-6, and TNF-α mRNA and protein expressions were significantly reduced (P < 0.05). Conclusion Resveratrol can effectively improve MIRI, and its mechanism may be related to antioxidative stress and anti-inflammatory.
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Kitada M, Ogura Y, Monno I, Koya D. Supplementation with Red Wine Extract Increases Insulin Sensitivity and Peripheral Blood Mononuclear Sirt1 Expression in Nondiabetic Humans. Nutrients 2020; 12:nu12103108. [PMID: 33053742 PMCID: PMC7600896 DOI: 10.3390/nu12103108] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 09/28/2020] [Accepted: 10/09/2020] [Indexed: 02/07/2023] Open
Abstract
The aim of this study was to investigate the effects of dietary supplementation with a nonalcoholic red wine extract (RWE), including resveratrol and polyphenols, on insulin sensitivity and Sirt1 expression in nondiabetic humans. The present study was a single-arm, open-label and prospective study. Twelve subjects received supplementation with RWE, including 19.2 mg resveratrol and 136 mg polyphenols, daily for 8 weeks. After 8 weeks, metabolic parameters, including glucose/lipid metabolism and inflammatory markers, were evaluated. mRNA expression of Sirt1 was evaluated in isolated peripheral blood mononuclear cells (PBMNCs). Additionally, Sirt1 and phosphorylated AMP-activated kinase (p-AMPK) expression were evaluated in cultured human monocytes (THP-1 cells). Supplementation with RWE for 8 weeks decreased the homeostasis model assessment for insulin resistance (HOMA-IR), which indicates an increase in insulin sensitivity. Serum low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and interleukin-6 (IL-6) were significantly decreased by RWE supplementation for 8 weeks. Additionally, Sirt1 mRNA expression in isolated PBMNCs was significantly increased after 8 weeks of RWE supplementation. Moreover, the rate of increase in Sirt1 expression was positively correlated with the rate of change in HOMA-IR. The administration of RWE increased Sirt1 and p-AMPK expression in cultured THP-1 cells. Supplementation with RWE improved metabolism, such as insulin sensitivity, lipid profile and inflammation, in humans. Additionally, RWE supplementation induced an increase in Sirt1 expression in PBMNCs, which may be associated with an improvement in insulin sensitivity.
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Affiliation(s)
- Munehiro Kitada
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Daigaku, Uchinada, Ishikawa 920-0293, Japan; (Y.O.); (I.M.)
- Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Daigaku, Uchinada, Ishikawa 920-0293, Japan
- Correspondence: (M.K.); (D.K.); Tel.: +81-76-286-2211 (M.K. & D.K.); Fax: +81-76-286-6927 (M.K. & D.K.)
| | - Yoshio Ogura
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Daigaku, Uchinada, Ishikawa 920-0293, Japan; (Y.O.); (I.M.)
| | - Itaru Monno
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Daigaku, Uchinada, Ishikawa 920-0293, Japan; (Y.O.); (I.M.)
| | - Daisuke Koya
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Daigaku, Uchinada, Ishikawa 920-0293, Japan; (Y.O.); (I.M.)
- Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Daigaku, Uchinada, Ishikawa 920-0293, Japan
- Correspondence: (M.K.); (D.K.); Tel.: +81-76-286-2211 (M.K. & D.K.); Fax: +81-76-286-6927 (M.K. & D.K.)
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Park J, Kim J, Chen Y, Song HC, Chen Y, Zheng M, Surh YJ, Kim UH, Park JW, Joe Y, Chung HT. CO ameliorates cellular senescence and aging by modulating the miR-34a/Sirt1 pathway. Free Radic Res 2020; 54:848-858. [PMID: 32228197 DOI: 10.1080/10715762.2019.1710142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human diploid fibroblast WI-38 cells measured with SA-β-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-α IL-6, and PAI-1 and increased the transcriptional levels of antioxidant genes, such as HO-1 and NQO1. Moreover, CO apparently enhanced the expression of Sirt1 through down-regulation of miR-34a. Next, to determine whether Sirt1 mediates the inhibitory effect of CO on cellular senescence, we pre-treated WI-38 cells with the Sirt1 inhibitor Ex527 and a miR-34a mimic followed by the administration of H2O2 and evaluated the expression of SASP and antioxidant genes as well as ROS production. According to our results, Sirt1 is crucial for the antiaging and antioxidant effects of CO. Finally, CO prolonged the lifespan of Caenorhabditis elegans and delayed high-fat diet-induced liver aging. Taken together, these findings demonstrate that CO reduces cellular senescence and liver aging through the regulation of miR-34a and Sirt1.
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Affiliation(s)
- Jeongmin Park
- Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
| | - Jin Kim
- Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
| | - Yingqing Chen
- National Creative Research Laboratory for Ca2+ Signaling Network, Chonbuk National University Medical School, Jeonju, Republic of Korea.,Department of Pharmacology, Dalian University Medical College, Dalian, China
| | - Hyun-Chul Song
- Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
| | - Yubing Chen
- Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
| | - Min Zheng
- Department of Neurology, Affliated Hospital of Yanbian University, Yanji, China
| | - Young-Joon Surh
- Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
| | - Uh-Hyun Kim
- National Creative Research Laboratory for Ca2+ Signaling Network, Chonbuk National University Medical School, Jeonju, Republic of Korea
| | - Jeong Woo Park
- Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
| | - Yeonsoo Joe
- Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
| | - Hun Taeg Chung
- Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
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Farooq MA, Gaertner S, Amoura L, Niazi ZR, Park SH, Qureshi AW, Oak MH, Toti F, Schini-Kerth VB, Auger C. Intake of omega-3 formulation EPA:DHA 6:1 by old rats for 2 weeks improved endothelium-dependent relaxations and normalized the expression level of ACE/AT1R/NADPH oxidase and the formation of ROS in the mesenteric artery. Biochem Pharmacol 2019; 173:113749. [PMID: 31830469 DOI: 10.1016/j.bcp.2019.113749] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/06/2019] [Indexed: 01/21/2023]
Abstract
Omega-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to protect the cardiovascular system, in part, by stimulating the endothelial formation of nitric oxide (NO). EPA:DHA 6:1 has been identified as a potent omega 3 PUFA formulation to induce endothelium-dependent vasorelaxation and activation of endothelial NO synthase (eNOS). This study examined whether intake of EPA:DHA 6:1 (500 mg/kg/day) for 2 weeks improves an established endothelial dysfunction in old rats (20 months old), and, if so, the underlying mechanism was subsequently determined. In the main mesenteric artery rings, an endothelial dysfunction characterized by a blunted NO component, an abolished endothelium-dependent hyperpolarization component, and increased endothelium-dependent contractile responses (EDCFs) are observed in old rats compared to young rats. Age-related endothelial dysfunction was associated with increased vascular formation of reactive oxygen species (ROS) and expression of eNOS, components of the local angiotensin system, senescence markers, and cyclooxygenase-2 (COX-2), and the downregulation of COX-1. The EPA:DHA 6:1 treatment improved the NO-mediated relaxation, reduced the EDCF-dependent contractile response and the vascular formation of ROS, and normalized the expression level of all target proteins in the old arterial wall. Thus, the present findings indicate that a 2-week intake of EPA:DHA 6:1 by old rats restored endothelium-dependent NO-mediated relaxations, most likely, by preventing the upregulation of the local angiotensin system and the subsequent formation of ROS.
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Affiliation(s)
- Muhammad A Farooq
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France
| | - Sébastien Gaertner
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Hôpitaux Universitaire de Strasbourg (HUS), Service des Maladies Vasculaires - Hypertension Artérielle, 67000 Strasbourg, France
| | - Lamia Amoura
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France
| | - Zahid R Niazi
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France
| | - Sin-Hee Park
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France
| | - Abdul W Qureshi
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France
| | - Min-Ho Oak
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France
| | - Florence Toti
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France
| | - Valérie B Schini-Kerth
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France; Hôpitaux Universitaire de Strasbourg (HUS), Service des Maladies Vasculaires - Hypertension Artérielle, 67000 Strasbourg, France
| | - Cyril Auger
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 67000 Strasbourg, France; Université de Strasbourg, Faculté de Pharmacie, 67000 Strasbourg, France.
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Mikhailova MV, Belyaeva NF, Kozlova NI, Zolotarev KV, Mikhailov AN, Berman AE, Archakov AI. [Protective action of fish muscle extracts against cellular senescence induced by oxidative stress]. BIOMEDIT︠S︡INSKAI︠A︡ KHIMII︠A︡ 2019; 63:351-355. [PMID: 28862607 DOI: 10.18097/pbmc20176304351] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Muscle extracts of some fish species, i.e. pike (Esox lucius), sterlet (Acipenser ruthenus), pink salmon (Oncorhynchus gorbuscha) and, to a lesser extent, perch (Perca fluviatilis) and Russian sturgeon, (Acipenser gueldenstaedtii) prevent the development of premature senescence of the human embryonic fibroblasts induced by the sublethal concentration of H2O2. Muscle extracts of other fish species tested, i.e. coho salmon (Oncorhynchus kisutch) and zander (Sander lucioperca), have not demonstrated this feature. Cell proliferation increased after the action of the senescence-inhibiting muscle extracts. Possible mechanisms of the action of nature biologically active compounds that interfere with the development of stress-induced cell senescence are discussed.
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Affiliation(s)
| | - N F Belyaeva
- Institute of Biomedical Chemistry, Moscow, Russia
| | - N I Kozlova
- Institute of Biomedical Chemistry, Moscow, Russia
| | | | | | - A E Berman
- Institute of Biomedical Chemistry, Moscow, Russia
| | - A I Archakov
- Institute of Biomedical Chemistry, Moscow, Russia
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Silva GC, Abbas M, Khemais-Benkhiat S, Burban M, Ribeiro TP, Toti F, Idris-Khodja N, Côrtes SF, Schini-Kerth VB. Replicative senescence promotes prothrombotic responses in endothelial cells: Role of NADPH oxidase- and cyclooxygenase-derived oxidative stress. Exp Gerontol 2017; 93:7-15. [PMID: 28412252 DOI: 10.1016/j.exger.2017.04.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 03/01/2017] [Accepted: 04/11/2017] [Indexed: 12/15/2022]
Abstract
Endothelial senescence has been suggested to promote endothelial dysfunction in age-related vascular disorders. This study evaluated the prothrombotic properties of senescent endothelial cells (ECs) and the underlying mechanism. Serial passaging from passage (P)1 to P4 (replicative senescence) of porcine coronary artery ECs, or treatment of P1 ECs with the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME (premature senescence) induced acquisition of markers of senescence including increased senescence-associated-β-galactosidase (SA-β-gal) activity and p53, p21, p16 expression. Approximately 55% of P3 cells were senescent with a high level oxidative stress, and decreased eNOS-derived nitric oxide (NO) formation associated with increased expression of NADPH oxidase subunits (gp91phox, p47phox), cyclooxygenase (COX)-2 but not COX-1, and a decreased eNOS expression leading to a reduced ability of ECs to inhibit platelet aggregation. P3 cells also presented increased expression and activity of tissue factor (TF), a key initiator of the coagulation cascade. Treatment of senesecent cells with a NADPH oxidase inhibitor (VAS-2870) or by a COX inhibitor (indomethacin) reduced oxidative stress, decreased TF activity and expression, and reduced the expression of gp91phox, p47phox and COX-2 and restored the ability of ECs to inhibit effectively platelet aggregation. Thus, replicative endothelial senescence promotes a prothrombotic response involving the down-regulation of the protective NO pathway and the upregulation of the NADPH oxidase- and COXs-dependent oxidative stress pathway promoting TF expression and activity.
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Affiliation(s)
- Grazielle Caroline Silva
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France; Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Malak Abbas
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France
| | - Sonia Khemais-Benkhiat
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France
| | - Melanie Burban
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France
| | - Thais Porto Ribeiro
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France
| | - Florence Toti
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France
| | - Noureddine Idris-Khodja
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France
| | - Steyner F Côrtes
- Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Valérie B Schini-Kerth
- Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, France.
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Health-beneficial nutraceuticals—myth or reality? Appl Microbiol Biotechnol 2017; 101:951-961. [DOI: 10.1007/s00253-016-8068-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 12/14/2016] [Accepted: 12/17/2016] [Indexed: 01/11/2023]
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12
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Polyphenols and DNA Damage: A Mixed Blessing. Nutrients 2016; 8:nu8120785. [PMID: 27918471 PMCID: PMC5188440 DOI: 10.3390/nu8120785] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 11/15/2016] [Accepted: 11/23/2016] [Indexed: 12/26/2022] Open
Abstract
Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds. A variety of assays are in use to study genetic damage endpoints. Human trials, of which there are rather few, tend to show decreases in endogenous DNA damage and protection against DNA damage induced ex vivo in blood cells. Most animal experiments have investigated the effects of polyphenols (often at high doses) in combination with known DNA-damaging agents, and generally they show protection. High concentrations can themselves induce DNA damage, as demonstrated in numerous cell culture experiments; low concentrations, on the other hand, tend to decrease DNA damage.
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MA YI, GONG XUN, MO YINGLI, WU SAIZHU. Polydatin inhibits the oxidative stress-induced proliferation of vascular smooth muscle cells by activating the eNOS/SIRT1 pathway. Int J Mol Med 2016; 37:1652-60. [DOI: 10.3892/ijmm.2016.2554] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2015] [Accepted: 03/28/2016] [Indexed: 11/06/2022] Open
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Khemais-Benkhiat S, Idris-Khodja N, Ribeiro TP, Silva GC, Abbas M, Kheloufi M, Lee JO, Toti F, Auger C, Schini-Kerth VB. The Redox-sensitive Induction of the Local Angiotensin System Promotes Both Premature and Replicative Endothelial Senescence: Preventive Effect of a Standardized Crataegus Extract. J Gerontol A Biol Sci Med Sci 2015; 71:1581-1590. [PMID: 26672612 DOI: 10.1093/gerona/glv213] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/03/2015] [Indexed: 11/13/2022] Open
Abstract
Endothelial senescence, characterized by an irreversible cell cycle arrest, oxidative stress, and downregulation of endothelial nitric oxide synthase (eNOS), has been shown to promote endothelial dysfunction leading to the development of age-related vascular disorders. This study has assessed the possibility that the local angiotensin system promotes endothelial senescence in coronary artery endothelial cells and also the protective effect of the Crataegus extract WS1442, a quantified hawthorn extract. Serial passaging from P1 to P4 (replicative senescence) and treatment of P1 endothelial cells with the eNOS inhibitor L-NAME (premature senescence) promoted acquisition of markers of senescence, enhanced ROS formation, decreased eNOS expression, and upregulation of angiotensin-converting enzyme (ACE) and AT1 receptors. Increased SA-β-gal activity and the upregulation of ACE and AT1R in senescent cells were prevented by antioxidants, an ACE inhibitor, and by an AT1 receptor blocker. WS1442 prevented SA-β-gal activity, the downregulation of eNOS, and oxidative stress in P3 cells. These findings indicate that the impairment of eNOS-derived nitric oxide formation favors a pro-oxidant response triggering the local angiotensin system, which, in turn, promotes endothelial senescence. Such a sequence of events can be effectively inhibited by a standardized polyphenol-rich extract mainly by targeting the oxidative stress.
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Affiliation(s)
- Sonia Khemais-Benkhiat
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Noureddine Idris-Khodja
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Thais Porto Ribeiro
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Grazielle Caroline Silva
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Malak Abbas
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France.,EA 7293 Stress Vasculaire et Tissulaire en Transplantation, Faculté de Pharmacie, Université de Strasbourg. Illkirch, France
| | - Marouane Kheloufi
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Jung-Ok Lee
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Florence Toti
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Cyril Auger
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
| | - Valérie B Schini-Kerth
- UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France.
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Santilli F, D'Ardes D, Davì G. Oxidative stress in chronic vascular disease: From prediction to prevention. Vascul Pharmacol 2015; 74:23-37. [DOI: 10.1016/j.vph.2015.09.003] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 09/04/2015] [Accepted: 09/08/2015] [Indexed: 12/14/2022]
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16
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Phosphodiesterase 1 regulation is a key mechanism in vascular aging. Clin Sci (Lond) 2015; 129:1061-75. [PMID: 26464516 DOI: 10.1042/cs20140753] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 06/25/2015] [Indexed: 12/31/2022]
Abstract
Reduced nitric oxide (NO)/cGMP signalling is observed in age-related vascular disease. We hypothesize that this disturbed signalling involves effects of genomic instability, a primary causal factor in aging, on vascular smooth muscle cells (VSMCs) and that the underlying mechanism plays a role in human age-related vascular disease. To test our hypothesis, we combined experiments in mice with genomic instability resulting from the defective nucleotide excision repair gene ERCC1 (Ercc1(d/-) mice), human VSMC cultures and population genome-wide association studies (GWAS). Aortic rings of Ercc1(d/-) mice showed 43% reduced responses to the soluble guanylate cyclase (sGC) stimulator sodium nitroprusside (SNP). Inhibition of phosphodiesterase (PDE) 1 and 5 normalized SNP-relaxing effects in Ercc1(d/-) to wild-type (WT) levels. PDE1C levels were increased in lung and aorta. cGMP hydrolysis by PDE in lungs was higher in Ercc1(d/-) mice. No differences in activity or levels of cGMP-dependent protein kinase 1 or sGC were observed in Ercc1(d/-) mice compared with WT. Senescent human VSMC showed elevated PDE1A and PDE1C and PDE5 mRNA levels (11.6-, 9- and 2.3-fold respectively), which associated with markers of cellular senescence. Conversely, PDE1 inhibition lowered expression of these markers. Human genetic studies revealed significant associations of PDE1A single nucleotide polymorphisms with diastolic blood pressure (DBP; β=0.28, P=2.47×10(-5)) and carotid intima-media thickness (cIMT; β=-0.0061, P=2.89×10(-5)). In summary, these results show that genomic instability and cellular senescence in VSMCs increase PDE1 expression. This might play a role in aging-related loss of vasodilator function, VSMC senescence, increased blood pressure and vascular hypertrophy.
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Abenavoli L, Milic N, Peta V, Alfieri F, De Lorenzo A, Bellentani S. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet. World J Gastroenterol 2014; 20:16831-16840. [PMID: 25492997 PMCID: PMC4258553 DOI: 10.3748/wjg.v20.i45.16831] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Revised: 07/20/2014] [Accepted: 09/16/2014] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The mechanisms of the underlying disease development and progression are awaiting clarification. Insulin resistance and obesity-related inflammation status, among other possible genetic, dietary, and lifestyle factors, are thought to play the key role. There is no consensus concerning the pharmacological treatment. However, the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy. On the basis of its components, the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases, including obesity and diabetes. New evidence supports the idea that the Mediterranean diet, associated with physical activity and cognitive behaviour therapy, may have an important role in the prevention and the treatment of NAFLD.
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Lee J, Jo DG, Park D, Chung HY, Mattson MP. Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev 2014; 66:815-68. [PMID: 24958636 PMCID: PMC4081729 DOI: 10.1124/pr.113.007757] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-κB, hypoxia-inducible factor 1α, peroxisome proliferator-activated receptor γ, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied.
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Affiliation(s)
- Jaewon Lee
- Department of Pharmacy, College of Pharmacy, and Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Geumjeong-gu, Busan, Republic of Korea (J.L., D.P., H.Y.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea (D.-G.J.); Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland (M.P.M.); and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (M.P.M.)
| | - Dong-Gyu Jo
- Department of Pharmacy, College of Pharmacy, and Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Geumjeong-gu, Busan, Republic of Korea (J.L., D.P., H.Y.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea (D.-G.J.); Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland (M.P.M.); and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (M.P.M.)
| | - Daeui Park
- Department of Pharmacy, College of Pharmacy, and Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Geumjeong-gu, Busan, Republic of Korea (J.L., D.P., H.Y.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea (D.-G.J.); Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland (M.P.M.); and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (M.P.M.)
| | - Hae Young Chung
- Department of Pharmacy, College of Pharmacy, and Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Geumjeong-gu, Busan, Republic of Korea (J.L., D.P., H.Y.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea (D.-G.J.); Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland (M.P.M.); and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (M.P.M.)
| | - Mark P Mattson
- Department of Pharmacy, College of Pharmacy, and Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Geumjeong-gu, Busan, Republic of Korea (J.L., D.P., H.Y.C.); School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea (D.-G.J.); Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland (M.P.M.); and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (M.P.M.)
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Wu H, Roks AJ. Genomic instability and vascular aging: A focus on nucleotide excision repair. Trends Cardiovasc Med 2014; 24:61-8. [DOI: 10.1016/j.tcm.2013.06.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Revised: 06/19/2013] [Accepted: 06/20/2013] [Indexed: 11/26/2022]
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Gordish KL, Beierwaltes WH. Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging. Am J Physiol Renal Physiol 2014; 306:F542-50. [PMID: 24431202 DOI: 10.1152/ajprenal.00437.2013] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min(-1)·gram of kidney weight(-1) (gkw); n = 8; P < 0.002] and decreased renal vascular resistance (RVR) by 18% from 15.00 ± 1.65 to 12.32 ± 1.20 arbitrary resistance units (ARU; P < 0.002). To test the participation of NO, we administered 5.0 mg/kg bw resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min(-1)·gkw(-1); n = 10; P < 0.001). To test the participation of ROS, we gave 5.0 mg/kg bw resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min(-1)·gkw(-1); n = 7; P < 0.001) and decreased RVR 19% (from 18.83 ± 1.37 to 15.27 ± 1.37 ARU). Tempol blocked resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min(-1)·gkw(-1); n = 7; P < 0.03) and the decrease in RVR posttempol was 44% of the control response (3.56 ± 0.34 vs. 1.57 ± 0.21 ARU; n = 7; P < 0.006). We also tested the role of endothelium-derived prostanoids. Two days of 10 mg/kg bw indomethacin pretreatment did not alter basal blood pressure or RBF. Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products.
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Affiliation(s)
- Kevin L Gordish
- Dept. Internal Medicine, Hypertension and Vascular Research Div., Henry Ford Hospital, 7088 E&R Bldg., 2799 W. Grand Blvd., Detroit, MI 48202.
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Hwang JW, Yao H, Caito S, Sundar IK, Rahman I. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med 2013; 61:95-110. [PMID: 23542362 PMCID: PMC3762912 DOI: 10.1016/j.freeradbiomed.2013.03.015] [Citation(s) in RCA: 387] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2012] [Revised: 12/06/2012] [Accepted: 03/20/2013] [Indexed: 12/31/2022]
Abstract
Sirtuin 1 (SIRT1) regulates inflammation, aging (life span and health span), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging, in which oxidative stress occurs. SIRT1 is regulated by a NAD(+)-dependent DNA repair enzyme, poly(ADP-ribose) polymerase-1 (PARP1), and subsequent NAD(+) depletion by oxidative stress may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to posttranslational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65, and FOXO3, thereby enhancing the inflammatory, prosenescent, and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox posttranslational modifications of SIRT1 and its roles in PARP1 and NF-κB activation, and FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging, are discussed. Furthermore, we have also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases.
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Affiliation(s)
- Jae-woong Hwang
- Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Hongwei Yao
- Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Samuel Caito
- Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Isaac K Sundar
- Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Irfan Rahman
- Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
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Stenvinkel P, Larsson TE. Chronic kidney disease: a clinical model of premature aging. Am J Kidney Dis 2013; 62:339-51. [PMID: 23357108 DOI: 10.1053/j.ajkd.2012.11.051] [Citation(s) in RCA: 224] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Accepted: 11/19/2012] [Indexed: 12/21/2022]
Abstract
Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population.
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Affiliation(s)
- Peter Stenvinkel
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
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Lei J, Gu X, Ye Z, Shi J, Zheng X. Antiaging effects of simvastatin on vascular endothelial cells. Clin Appl Thromb Hemost 2012; 20:212-8. [PMID: 22964779 DOI: 10.1177/1076029612458967] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The anti-inflammatory, antioxidative, and antiarteriosclerosis activities of simvastatin along with its protective effects on the endothelium suggest that it may also have antiaging effects. The aim of this study was to investigate the antiaging effects of simvastatin as well as its effects on sirtuin 1 (SIRT1) expression in endothelial cells. Aged rats and human umbilical vein endothelial cells were treated with simvastatin in the presence and absence of oxidized low-density lipoprotein (OX-LDL). Aortic β-galactosidase staining was undertaken to determine senescence, and SIRT1 protein expression was evaluated using Western blot analysis. After simvastatin therapy, arterial endothelial cell aging was significantly reduced, and SIRT1 expression was significantly increased. The OX-LDL significantly accelerated the senescence of umbilical vein endothelial cells and decreased SIRT1 expression. The OX-LDL-induced downregulation of SIRT1 was blocked by simvastatin. Simvastatin treatment also reduced umbilical vein endothelial cell aging and increased SIRT1 expression.
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Affiliation(s)
- Junping Lei
- 1Department of Cardiovascular Diseases, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
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