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1
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Wong WK, Ren Y, Leung FKC. Photothermal-chemotherapy: the emerging supramolecular photothermal molecules and the recent advances. NANOPHOTOTHERAPY 2025:463-499. [DOI: 10.1016/b978-0-443-13937-6.00007-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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2
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Guo Y, Li L, Yan S, Shi B. Plant Extracts to Alleviating Heat Stress in Dairy Cows. Animals (Basel) 2023; 13:2831. [PMID: 37760231 PMCID: PMC10525364 DOI: 10.3390/ani13182831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/31/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
Heat stress (HS) in cows is a critical issue in the dairy industry. Dairy cows accumulate heat from body metabolism, along with that imposed by air temperature, humidity, air flow and solar radiation. HS in animals can occur during hot and humid summers when the ambient temperature is extremely high. Dairy cows have relatively high feed intakes and metabolic heat production and are thus susceptible to HS, leading to reductions in feed intake, lower milk yield, affected milk quality, reduced animal health and even shortening the productive lifespan of cows. Therefore, alleviating HS is a top priority for the dairy industry. Suitable plant extracts have advantages in safety, efficiency and few toxic side effects or residues for applications to alleviate HS in dairy cows. This paper reviews the effects of some plant extract products on alleviating HS in dairy cows and briefly discusses their possible mechanisms of action.
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Affiliation(s)
| | | | - Sumei Yan
- Key Laboratory of Animal Nutrition and Feed Science at University of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
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3
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Madelaire CB, Klink AC, Israelsen WJ, Hindle AG. Fibroblasts as an experimental model system for the study of comparative physiology. Comp Biochem Physiol B Biochem Mol Biol 2022; 260:110735. [PMID: 35321853 DOI: 10.1016/j.cbpb.2022.110735] [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: 12/30/2021] [Revised: 03/15/2022] [Accepted: 03/17/2022] [Indexed: 10/18/2022]
Abstract
Mechanistic evaluations of processes that underlie organism-level physiology often require reductionist approaches. Dermal fibroblasts offer one such approach. These cells are easily obtained from minimally invasive skin biopsy, making them appropriate for the study of protected and/or logistically challenging species. Cell culture approaches permit extensive and fine-scale sampling regimes as well as gene manipulation techniques that are not feasible in vivo. Fibroblast isolation and culture protocols are outlined here for primary cells, and the benefits and drawbacks of immortalization are discussed. We show examples of physiological metrics that can be used to characterize primary cells (oxygen consumption, translation, proliferation) and readouts that can be informative in understanding cell-level responses to environmental stress (lactate production, heat shock protein induction). Importantly, fibroblasts may display fidelity to whole animal physiological phenotypes, facilitating their study. Fibroblasts from Antarctic Weddell seals show greater resilience to low temperatures and hypoxia exposure than fibroblasts from humans or rats. Fibroblast oxygen consumption rates are not affected by temperature stress in the heat-tolerant camel, whereas similar temperature exposures depress mitochondrial metabolism in fibroblasts from rhinoceros. Finally, dermal fibroblasts from a hibernator, the meadow jumping mouse, better resist experimental cooling than a fibroblast line from the laboratory mouse, with the hibernator demonstrating a greater maintenance of homeostatic processes such as protein translation. These results exemplify the parallels that can be drawn between fibroblast physiology and expectations in vivo, and provide evidence for the power of fibroblasts as a model system to understand comparative physiology and biomedicine.
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Affiliation(s)
- Carla B Madelaire
- School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA
| | - Amy C Klink
- School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA
| | - William J Israelsen
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA; Skroot Laboratory, Inc., Ames, IA, USA
| | - Allyson G Hindle
- School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA.
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4
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Bouchama A, Abuyassin B, Lehe C, Laitano O, Jay O, O'Connor FG, Leon LR. Classic and exertional heatstroke. Nat Rev Dis Primers 2022; 8:8. [PMID: 35115565 DOI: 10.1038/s41572-021-00334-6] [Citation(s) in RCA: 186] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/20/2021] [Indexed: 12/28/2022]
Abstract
In the past two decades, record-breaking heatwaves have caused an increasing number of heat-related deaths, including heatstroke, globally. Heatstroke is a heat illness characterized by the rapid rise of core body temperature above 40 °C and central nervous system dysfunction. It is categorized as classic when it results from passive exposure to extreme environmental heat and as exertional when it develops during strenuous exercise. Classic heatstroke occurs in epidemic form and contributes to 9-37% of heat-related fatalities during heatwaves. Exertional heatstroke sporadically affects predominantly young and healthy individuals. Under intensive care, mortality reaches 26.5% and 63.2% in exertional and classic heatstroke, respectively. Pathological studies disclose endothelial cell injury, inflammation, widespread thrombosis and bleeding in most organs. Survivors of heatstroke may experience long-term neurological and cardiovascular complications with a persistent risk of death. No specific therapy other than rapid cooling is available. Physiological and morphological factors contribute to the susceptibility to heatstroke. Future research should identify genetic factors that further describe individual heat illness risk and form the basis of precision-based public health response. Prioritizing research towards fundamental mechanism and diagnostic biomarker discovery is crucial for the design of specific management approaches.
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Affiliation(s)
- Abderrezak Bouchama
- King Abdullah International Medical Research Center, Experimental Medicine Department, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia.
| | - Bisher Abuyassin
- King Abdullah International Medical Research Center, Experimental Medicine Department, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia
| | - Cynthia Lehe
- King Abdullah International Medical Research Center, Experimental Medicine Department, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia
| | - Orlando Laitano
- Department of Nutrition & Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, USA
| | - Ollie Jay
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Francis G O'Connor
- Military and Emergency Medicine, Uniformed Services University, Bethesda, MD, USA
| | - Lisa R Leon
- Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
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5
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Araki Y, Ida Y, Nonaka M, Yoshizaki Y, Fujii A, Nagano M, Kanouchi H. The Induction of Heat Shock Protein 70 after Oral Administration of Concentrated Brewed Rice Vinegar Kurozu in Mice. J Nutr Sci Vitaminol (Tokyo) 2021; 66:478-480. [PMID: 33132352 DOI: 10.3177/jnsv.66.478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Heat shock protein 70 (HSP70) is induced by various stresses. Since HSP70 has a protein refolding activity and an anti-inflammatory activity, the HSP70 induction will help cells from harmful acute stresses. Feeding a diet containing concentrated brewed rice vinegar Kurozu (CK) diet for 5 wk resulted in an increase of HSP70 in the brains of mice. In the present study, we evaluated whether oral feeding of 25 μL CK induces HSP70 mRNA in brain and other tissues. HSP70 mRNA was significantly increased in the esophagus, small intestine, liver, and brown adipose tissue within 1 h after the oral administration of CK. A weaker induction of HSP70 mRNA was demonstrated in the stomach, large intestine, and brain. HSP70 mRNA induction returned to basal levels within 3 h after feeding. We doubted that the induction of HSP70 mRNA was caused by manual restraint of the mice during CK administration. Manual restraint of the mice did not influence HSP70 mRNA expression in intestine 1 h after these treatments. Our results suggest that transient HSP70 mRNA induction by oral feeding of CK was not caused by retention stress. There are some compounds in CK that increase HSP70 mRNA in various tissues.
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Affiliation(s)
- Yuri Araki
- Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University
| | - Yuta Ida
- Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University
| | - Miwa Nonaka
- Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University
| | - Yumiko Yoshizaki
- Education and Research Center for Fermentation Studies, Faculty of Agriculture, Kagoshima University
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6
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Shan Q, Ma F, Wei J, Li H, Ma H, Sun P. Physiological Functions of Heat Shock Proteins. Curr Protein Pept Sci 2021; 21:751-760. [PMID: 31713482 DOI: 10.2174/1389203720666191111113726] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 05/24/2019] [Accepted: 09/21/2019] [Indexed: 01/03/2023]
Abstract
Heat shock proteins (HSPs) are molecular chaperones involved in a variety of life activities. HSPs function in the refolding of misfolded proteins, thereby contributing to the maintenance of cellular homeostasis. Heat shock factor (HSF) is activated in response to environmental stresses and binds to heat shock elements (HSEs), promoting HSP translation and thus the production of high levels of HSPs to prevent damage to the organism. Here, we summarize the role of molecular chaperones as anti-heat stress molecules and their involvement in immune responses and the modulation of apoptosis. In addition, we review the potential application of HSPs to cancer therapy, general medicine, and the treatment of heart disease.
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Affiliation(s)
- Qiang Shan
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences,
Beijing, 100193, China
| | - Fengtao Ma
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences,
Beijing, 100193, China
| | - Jingya Wei
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences,
Beijing, 100193, China
| | - Hongyang Li
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences,
Beijing, 100193, China
| | - Hui Ma
- Beijing Sunlon Livestock Development Co., Ltd, Beijing, China
| | - Peng Sun
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences,
Beijing, 100193, China
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7
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Expression of Heat Shock Protein 70 Is Insufficient To Extend Drosophila melanogaster Longevity. G3-GENES GENOMES GENETICS 2019; 9:4197-4207. [PMID: 31624139 PMCID: PMC6893204 DOI: 10.1534/g3.119.400782] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
It has been known for over 20 years that Drosophila melanogaster flies with twelve additional copies of the hsp70 gene encoding the 70 kD heat shock protein lives longer after a non-lethal heat treatment. Since the heat treatment also induces the expression of additional heat shock proteins, the biological effect can be due either to HSP70 acting alone or in combination. This study used the UAS/GAL4 system to determine whether hsp70 is sufficient to affect the longevity and the resistance to thermal, oxidative or desiccation stresses of the whole organism. We observed that HSP70 expression in the nervous system or muscles has no effect on longevity or stress resistance but ubiquitous expression reduces the life span of males. We also observed that the down-regulation of hsp70 using RNAi did not affect longevity.
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8
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Abstract
Antibodies can be developed to directly inhibit almost any protein, but their inability to enter the cytosol limits inhibitory antibodies to membrane-associated or extracellular targets. Developing a cytosolic antibody delivery system would offer unique opportunities to directly inhibit and study intracellular protein function. Here we demonstrate that IgG antibodies that are conjugated with anionic polypeptides (ApPs) can be complexed with cationic lipids originally designed for nucleic acid delivery through electrostatic interactions, enabling close to 90% cytosolic delivery efficiency with only 500 nM IgG. The ApP is fused to a small photoreactive antibody-binding domain (pAbBD) that can be site-specifically photocrosslinked to nearly all off-the-shelf IgGs, enabling easy exchange of cargo IgGs. We show that cytosolically delivered IgGs can inhibit the drug efflux pump multidrug resistance-associated protein 1 (MRP1) and the transcription factor NFκB. This work establishes an approach for using existing antibody collections to modulate intracellular protein function.
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9
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Chiaramonte M, Inguglia L, Vazzana M, Deidun A, Arizza V. Stress and immune response to bacterial LPS in the sea urchin Paracentrotus lividus (Lamarck, 1816). FISH & SHELLFISH IMMUNOLOGY 2019; 92:384-394. [PMID: 31220574 DOI: 10.1016/j.fsi.2019.06.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 06/07/2019] [Accepted: 06/10/2019] [Indexed: 06/09/2023]
Abstract
The immune system of the sea urchin species Paracentrotus lividus is highly complex and, as yet, poorly understood. P. lividus coelomocytes mediate immune response through phagocytosis and encapsulation of non-self particles, in addition to the production of antimicrobial molecules. Despite this understanding, details of exactly how these processes occur and the mechanisms which drive them are still in need of clarification. In this study, we show how the bacterial lipopolysaccharides (LPS) is able to induce a stress response which increases the levels of the heat shock proteins HSP70 and HSP90 only a few hours after treatment. This study also shows that LPS treatment increases the expression of the β-thymosin-derivated protein paracentrin, the precursor of antimicrobial peptides.
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Affiliation(s)
- Marco Chiaramonte
- Dept. STEBICEF, Università Degli Studi di Palermo, Via Archirafi, 18, 90123, Palermo, Italy
| | - Luigi Inguglia
- Dept. STEBICEF, Università Degli Studi di Palermo, Via Archirafi, 18, 90123, Palermo, Italy.
| | - Mirella Vazzana
- Dept. STEBICEF, Università Degli Studi di Palermo, Via Archirafi, 18, 90123, Palermo, Italy
| | - Alan Deidun
- Dept. of Geosciences, University of Malta, Msida, MSD, 2080, Malta
| | - Vincenzo Arizza
- Dept. STEBICEF, Università Degli Studi di Palermo, Via Archirafi, 18, 90123, Palermo, Italy
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10
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Zheng J, Nie H, Yan X. Analysis of differential gene expression by SRAP-cDNA in mantle tissue of Meretrix petechialis with different external shell color. Anim Biotechnol 2019; 32:31-37. [PMID: 31328641 DOI: 10.1080/10495398.2019.1642907] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Gene expression of two shell colors in Meretrix petechialis were analyzed by sequence related amplified polymorphism-cDNA to screen the associated molecular markers. The two shell color genomes of M. petechialis were amplified using combinations of 30 primers; 11 pairs of primers showed differential fragments, and by recovery, cloning and sequencing, 18 different differential sequences were obtained. The sequencing results were analyzed by BlastX. Only one fragment shared high homology with memory-related protein-2 and TonB-dependent receptor was found that related to shell color. Sequence characterized amplified region primers were designed according to the difference sequences, and PCR amplification was performed in both 'yellow' and 'red' M. petechialis. Four pairs of differential primers were obtained. Using the population to verify the four markers (Me1-Em2, Me2-Em3, Me4-The Em11 and Me4-Em12), it was found that Me1-Em2 and Me2-Em3 were positive in the 'yellow' and Me4-The Em11 and Me4-Em12 were positive in the 'red' M. petechialis populations. All four markers can, therefore, be used as M. petechialis shell color related markers. This provides a theoretical basis for studying shell color regulation in M. petechialis, which may help to reveal the underlying molecular mechanisms more comprehensively.
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Affiliation(s)
- Junhong Zheng
- College of Fisheries and Life Science, Engineering and Technology Research Center of Shellfish Breeding in Liaoning Province, Dalian Ocean University, Dalian, 116023, China
| | - Hongtao Nie
- College of Fisheries and Life Science, Engineering and Technology Research Center of Shellfish Breeding in Liaoning Province, Dalian Ocean University, Dalian, 116023, China
| | - Xiwu Yan
- College of Fisheries and Life Science, Engineering and Technology Research Center of Shellfish Breeding in Liaoning Province, Dalian Ocean University, Dalian, 116023, China
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11
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Shevtsov M, Multhoff G. Therapeutic Implications of Heat Shock Proteins in Cancer. HEAT SHOCK PROTEINS 2019. [DOI: 10.1007/978-3-030-02254-9_11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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12
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Li X, Yu Y, Gorshkov B, Haigh S, Bordan Z, Weintraub D, Rudic RD, Chakraborty T, Barman SA, Verin AD, Su Y, Lucas R, Stepp DW, Chen F, Fulton DJR. Hsp70 Suppresses Mitochondrial Reactive Oxygen Species and Preserves Pulmonary Microvascular Barrier Integrity Following Exposure to Bacterial Toxins. Front Immunol 2018; 9:1309. [PMID: 29951058 PMCID: PMC6008539 DOI: 10.3389/fimmu.2018.01309] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 05/25/2018] [Indexed: 01/22/2023] Open
Abstract
Pneumonia is a leading cause of death in children and the elderly worldwide, accounting for 15% of all deaths of children under 5 years old. Streptococcus pneumoniae is a common and aggressive cause of pneumonia and can also contribute to meningitis and sepsis. Despite the widespread use of antibiotics, mortality rates for pneumonia remain unacceptably high in part due to the release of bacterial toxins. Pneumolysin (PLY) is a cholesterol-dependent toxin that is produced by Streptococcus, and it is both necessary and sufficient for the development of the extensive pulmonary permeability edema that underlies acute lung injury. The mechanisms by which PLY disrupts the pulmonary endothelial barrier are not fully understood. Previously, we found that reactive oxygen species (ROS) contribute to the barrier destructive effects of PLY and identified an unexpected but potent role of Hsp70 in suppressing ROS production. The ability of Hsp70 to influence PLY-induced barrier dysfunction is not yet described, and the goal of the current study was to identify whether Hsp70 upregulation is an effective strategy to protect the lung microvascular endothelial barrier from G+ bacterial toxins. Overexpression of Hsp70 via adenovirus-mediated gene transfer attenuated PLY-induced increases in permeability in human lung microvascular endothelial cells (HLMVEC) with no evidence of cytotoxicity. To adopt a more translational approach, we employed a pharmacological approach using geranylgeranylacetone (GGA) to acutely upregulate endogenous Hsp70 expression. Following acute treatment (6 h) with GGA, HLMVECs exposed to PLY displayed improved cell viability and enhanced endothelial barrier function as measured by both Electric Cell-substrate Impedance Sensing (ECIS) and transwell permeability assays compared to control treated cells. PLY promoted increased mitochondrial ROS, decreased mitochondrial oxygen consumption, and increased caspase 3 cleavage and cell death, which were collectively improved in cells pretreated with GGA. In mice, IP pretreatment with GGA 24 h prior to IT administration of PLY resulted in significantly less Evans Blue Dye extravasation compared to vehicle, indicating preserved endothelial barrier integrity and suggesting that the acute upregulation of Hsp70 may be an effective therapeutic approach in the treatment of lung injury associated with pneumonia.
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Affiliation(s)
- Xueyi Li
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia
| | - Yanfang Yu
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia.,Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Boris Gorshkov
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia
| | - Stephen Haigh
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia
| | - Zsuzsanna Bordan
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia
| | - Daniel Weintraub
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia
| | - Radu Daniel Rudic
- Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA, United States
| | - Trinad Chakraborty
- Institute for Medical Microbiology, Justus-Liebig University Giessen, Giessen, Germany
| | - Scott A Barman
- Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA, United States
| | - Alexander D Verin
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia
| | - Yunchao Su
- Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA, United States
| | - Rudolf Lucas
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia.,Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA, United States
| | - David W Stepp
- Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA, United States
| | - Feng Chen
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia.,Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - David J R Fulton
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia.,Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA, United States
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Xu J, Tang S, Song E, Yin B, Bao E. Inhibition of heat shock protein 70 intensifies heat-stressed damage and apoptosis of chicken primary myocardial cells in vitro. Mol Med Rep 2017; 15:2881-2889. [DOI: 10.3892/mmr.2017.6337] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 03/13/2017] [Indexed: 11/06/2022] Open
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14
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Saeed AL-Wajeeh N, Halabi MF, Hajrezaie M, M. Dhiyaaldeen S, Abdulaziz Bardi D, M. Salama S, Rouhollahi E, Karimian H, Abdolmalaki R, Azizan AHS, Mohd Ali H, Mohd Noor S, Abdulla MA. The Gastroprotective Effect of Vitex pubescens Leaf Extract against Ethanol-Provoked Gastric Mucosal Damage in Sprague-Dawley Rats. PLoS One 2016; 11:e0157431. [PMID: 27689880 PMCID: PMC5045201 DOI: 10.1371/journal.pone.0157431] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 05/30/2016] [Indexed: 12/26/2022] Open
Abstract
Vitex pubescens is a Malaysian therapeutic plant employed in traditional drug to remedy a variety of disorders. The purpose of this research is to assess the gastroprotective efficiency of V. pubescens leaves against ethanol-induced gastric hemorrhagic laceration in rats. Animals were randomly allocated into seven groups and pre-treated, separately, with 10% Tween 20 (normal and ulcer control groups), 20 mg/kg omeprazole (reference group), and 62.5, 125, 250, and 500 mg/kg of V. pubescens extract (experimental groups). All animals were sacrificed after another hour. Histological evaluation of the ulcer control group revealed significant injury to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. PAS staining, showed remarkably intense magenta color, remarkable increase of HSP70 and decrease of Bax proteins in rats pre-treated with plant extracts compared to the ulcer control group. Gastric homogenates revealed a remarkable increase in endogenous antioxidant enzyme activities (CAT, SOD, GSH) and a decrease in the lipid peroxidation level (MDA) in animals pre-treated with V. pubescens extract compared with the ulcer control group. The gastroprotective activity of this plant might be related to increased antioxidant enzymes and decrease lipid peroxidation upsurge of HSP70 and reduced expression of Bax proteins.
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Affiliation(s)
- Nahla Saeed AL-Wajeeh
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Mohammed Farouq Halabi
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Maryam Hajrezaie
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Summaya M. Dhiyaaldeen
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Daleya Abdulaziz Bardi
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Suzy M. Salama
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Elham Rouhollahi
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Hamed Karimian
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Rojin Abdolmalaki
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | | | - Hapipah Mohd Ali
- Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Suzita Mohd Noor
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Mahmood Ameen Abdulla
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
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15
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Wang S, Tian Y, Tian W, Sun J, Zhao S, Liu Y, Wang C, Tang Y, Ma X, Teng Z, Lu G. Selectively Sensitizing Malignant Cells to Photothermal Therapy Using a CD44-Targeting Heat Shock Protein 72 Depletion Nanosystem. ACS NANO 2016; 10:8578-90. [PMID: 27576159 DOI: 10.1021/acsnano.6b03874] [Citation(s) in RCA: 118] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
Selectively enhance the therapeutic efficacy to malignancy is one of the most important issues for photothermal therapy (PTT). However, most solid tumors, such as triple negative breast cancer (TNBC), do not have identifiable surface markers to distinguish themselves from normal cells, thus it is challenging to selectively identify and eliminate those malignances by PTT. In this report, we hypothesized that, by targeting CD44 (one TNBC-overexpressed surface molecule) and depleting heat shock protein 72 (HSP72, one malignancy-specific-overexpressed thermotolerance-related chaperone) subsequently, the TNBC could be selectively sensitized to PTT and improve the accuracy of treatment. To this end, a rationally designed nanosystem gold nanostar (GNS)/siRNA against HSP72 (siHSP72)/hyaluronic acid (HA) was successfully constructed using a layer-by-layer method. Hydrodynamic diameter and zeta potential analysis demonstrated the formation of GNS/siHSP72/HA having a particle size of 73.2 ± 3.8 nm and a negative surface charge of -18.3 ± 1.6 mV. The CD44-targeting ability of GNS/siHSP72/HA was confirmed by the flow cytometer, confocal microscopic imaging, and competitive binding analysis. The HSP72 silencing efficacy of GNS/siHSP72/HA was ∼95% in complete culture medium. By targeting CD44 and depleting HSP72 sequentially, GNS/siHSP72/HA could selectively sensitize TNBC cells to hyperthermia and enhance the therapeutic efficacy to TNBC with minimal side effect both in vitro and in vivo. Other advantages of GNS/siHSP72/HA included easy synthesis, robust siRNA loading capacity, endosome/lysosome escaping ability, high photothermal conversion efficacy and superior hemo- and biocompatibility.
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Affiliation(s)
- Shouju Wang
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China
| | - Ying Tian
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China
| | - Wei Tian
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
| | - Jing Sun
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
| | - Shuang Zhao
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
| | - Ying Liu
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
| | - Chunyan Wang
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
| | - Yuxia Tang
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China
| | - Xingqun Ma
- PLA Cancer Center of Nanjing Bayi Hospital , Nanjing 210002, P.R. China
| | - Zhaogang Teng
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China
| | - Guangming Lu
- Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China
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Riba I, Gabrielyan B, Khosrovyan A, Luque A, Del Valls TA. The influence of ph and waterborne metals on egg fertilization of the blue mussel (Mytilus edulis), the oyster (Crassostrea gigas) and the sea urchin (Paracentrotus lividus). ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2016; 23:14580-14588. [PMID: 27068916 DOI: 10.1007/s11356-016-6611-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 03/31/2016] [Indexed: 06/05/2023]
Abstract
This study evaluated the combined effect of pH and metals on the egg fertilization process of two estuarine species, the blue mussel (Mytilus edulis), the oyster (Crassostrea gigas) and a marine species, the sea urchin (Paracentrotus lividus). The success of egg fertilization was examined after exposure of gametes to sediment extracts of various degrees of contamination at pH 6.0, 6.5, 7.0, 7.5 and 8.0. At the pH levels from 6.5 to 8.0, the egg fertilization of the different species demonstrated different sensitivity to metal and/or acidic exposure. In all species, the results revealed that egg fertilization was almost completely inhibited at pH 6.0. The egg fertilization of the blue mussel M. edulis was the least sensitive to the exposure while that of the sea urchin P. lividus demonstrated a concentration-dependent response to the pH levels from 6.5 to 8.0. The results of this study revealed that acidity increased the concentration of several metal ions (Cr, Ni, Cu, Zn, Cd, and Pb) but reduced its availability to the organisms, probably related to the reactivity of the ions with most non-metals or to the competition among metals and other waterborne constituents.
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Affiliation(s)
- Inmaculada Riba
- UNESCO/UNITWIN WiCop, Department of Physical Chemistry, University of Cadiz, Poligono Río San Pedro, s/n, 11510, Puerto Real, Cádiz, Spain
| | - Bardukh Gabrielyan
- Scientific Center of Zoology and Hydrobiology, 7 Paruir Sevak, Yerevan, 0014, Armenia
| | - Alla Khosrovyan
- UNESCO/UNITWIN WiCop, Department of Physical Chemistry, University of Cadiz, Poligono Río San Pedro, s/n, 11510, Puerto Real, Cádiz, Spain.
| | - Angel Luque
- Department of Biology, University of Las Palmas de Gran Canaria, Tafira, Las Palmas, Spain
| | - T Angel Del Valls
- UNESCO/UNITWIN WiCop, Department of Physical Chemistry, University of Cadiz, Poligono Río San Pedro, s/n, 11510, Puerto Real, Cádiz, Spain
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Molecular Chaperones of Leishmania: Central Players in Many Stress-Related and -Unrelated Physiological Processes. BIOMED RESEARCH INTERNATIONAL 2015; 2015:301326. [PMID: 26167482 PMCID: PMC4488524 DOI: 10.1155/2015/301326] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2015] [Accepted: 05/24/2015] [Indexed: 12/12/2022]
Abstract
Molecular chaperones are key components in the maintenance of cellular homeostasis and survival, not only during stress but also under optimal growth conditions. Folding of nascent polypeptides is supported by molecular chaperones, which avoid the formation of aggregates by preventing nonspecific interactions and aid, when necessary, the translocation of proteins to their correct intracellular localization. Furthermore, when proteins are damaged, molecular chaperones may also facilitate their refolding or, in the case of irreparable proteins, their removal by the protein degradation machinery of the cell. During their digenetic lifestyle, Leishmania parasites encounter and adapt to harsh environmental conditions, such as nutrient deficiency, hypoxia, oxidative stress, changing pH, and shifts in temperature; all these factors are potential triggers of cellular stress. We summarize here our current knowledge on the main types of molecular chaperones in Leishmania and their functions. Among them, heat shock proteins play important roles in adaptation and survival of this parasite against temperature changes associated with its passage from the poikilothermic insect vector to the warm-blooded vertebrate host. The study of structural features and the function of chaperones in Leishmania biology is providing opportunities (and challenges) for drug discovery and improving of current treatments against leishmaniasis.
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18
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Vazzana M, Siragusa T, Arizza V, Buscaino G, Celi M. Cellular responses and HSP70 expression during wound healing in Holothuria tubulosa (Gmelin, 1788). FISH & SHELLFISH IMMUNOLOGY 2015; 42:306-315. [PMID: 25463287 DOI: 10.1016/j.fsi.2014.11.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 10/01/2014] [Accepted: 11/12/2014] [Indexed: 06/04/2023]
Abstract
Wound repair is a key event in the regeneration mechanisms of echinoderms. We studied, at the behavioural, cellular and molecular levels, the wound healing processes in Holothuria tubulosa after injuries to the body wall. The experiments were performed for periods of up to 72 h, and various coelomocyte counts, as well as the expression of heat shock proteins (HS27, HSP70 and HSP90), were recorded. Dermal wound healing was nearly complete within 72 h. In the early stages, we observed the injured animals twisting their bodies to keep their injuries on the surface of the water for the extrusion of the buccal pedicles. At the cellular level, we found time-dependent variations in the circulating coelomocyte counts. After injury, in particular, we observed a significant increase in spherule cells at 2.5 h post-injury. Using the western blot method, we observed and reported that the wounds produced, compared with controls, a significant increase in HSP27 and HSP70 expression in coelomocytes, whereas HSP70 was increased in scar tissue and HSP90 was increased only in cell-free coelomic fluid. These results highlight that the wounds were responsible for the stress condition with the induction of cellular and biochemical responses.
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Affiliation(s)
- Mirella Vazzana
- Dept. STEBICEF, Università degli Studi di Palermo, Via Archirafi, 18, 90123 Palermo, Italy
| | - Tiziana Siragusa
- Dept. STEBICEF, Università degli Studi di Palermo, Via Archirafi, 18, 90123 Palermo, Italy
| | - Vincenzo Arizza
- Dept. STEBICEF, Università degli Studi di Palermo, Via Archirafi, 18, 90123 Palermo, Italy; IEMEST - Istituto Euromediterraneo di Scienza e Tecnologia, Palermo, Italy.
| | - Giuseppa Buscaino
- IAMC - Istituto per l'Ambiente Marino Costiero U.O. di Capo Granitola - Consiglio Nazionale delle Ricerche, Via del Mare, 3, 91021 Torretta Granitola, TP, Italy
| | - Monica Celi
- Dept. STEBICEF, Università degli Studi di Palermo, Via Archirafi, 18, 90123 Palermo, Italy; IAMC - Istituto per l'Ambiente Marino Costiero U.O. di Capo Granitola - Consiglio Nazionale delle Ricerche, Via del Mare, 3, 91021 Torretta Granitola, TP, Italy
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19
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Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness. Amino Acids 2014; 46:1491-9. [DOI: 10.1007/s00726-014-1721-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Accepted: 03/03/2014] [Indexed: 10/25/2022]
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Heat shock protein 72 expressing stress in sepsis: unbridgeable gap between animal and human studies--a hypothetical "comparative" study. BIOMED RESEARCH INTERNATIONAL 2014; 2014:101023. [PMID: 24524071 PMCID: PMC3912989 DOI: 10.1155/2014/101023] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Accepted: 10/05/2013] [Indexed: 01/30/2023]
Abstract
Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical “comparative study” model.
Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies (P < 0.0001) were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P < 0.0001). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (P < 0.001). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (P < 0.02), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.
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Mansilla MJ, Comabella M, Río J, Castilló J, Castillo M, Martin R, Montalban X, Espejo C. Up-regulation of inducible heat shock protein-70 expression in multiple sclerosis patients. Autoimmunity 2013; 47:127-33. [PMID: 24328534 DOI: 10.3109/08916934.2013.866104] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Inducible heat shock protein (HSP)70 (HSP70-1A and HSP70-1B proteins) is a chaperone responsible for assisting proper protein folding. Following stress conditions, HSP70 is highly up-regulated to mediate cytoprotective functions. In addition, HSP70 is able to trigger innate and adaptive immune responses that promote the immune recognition of antigens and to act as a cytokine when it is released. The data in the literature are controversial with regard to expression studies in peripheral blood mononuclear cells (PBMCs). In the present study, we aimed to examine if alterations of HSP70-1A/B expression are involved in the autoimmune pathogenesis of multiple sclerosis (MS). We determined both mRNA and protein expression in PBMCs of MS patients and healthy donors (HDs). We found a baseline increased expression of the HSPA1A gene in PBMCs from MS patients compared with HDs. Gene expression findings were associated with an increased protein expression of HSP70-1A/B in T lymphocytes (CD4+ and CD8+) and monocytes from MS patients under basal conditions that may reflect the immunological activation occurring in MS patients. We also provided evidence that heat shock (HS) stimulus induced HSP70-1A/B protein expression in HDs and MS patients, and that HS-induced HSP70-1A/B protein expression in monocytes correlated with the number of T2 lesions at baseline in MS patients. However, after lipopolysaccharide inflammatory stimulus, monocytes from MS patients failed to induce HSP70-1A/B protein expression. Our data hint at altered immune responses in MS and may indicate either a state of chronic stress or increased vulnerability to physiological immune responses in MS patients.
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Affiliation(s)
- María José Mansilla
- Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (CEM-Cat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona , Barcelona , Spain and
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22
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Rohde MC, Corydon TJ, Hansen J, Pedersen CB, Schmidt SP, Gregersen N, Banner J. Heat stress and sudden infant death syndrome--stress gene expression after exposure to moderate heat stress. Forensic Sci Int 2013; 232:16-24. [PMID: 24053860 DOI: 10.1016/j.forsciint.2013.06.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2012] [Revised: 04/21/2013] [Accepted: 06/03/2013] [Indexed: 10/26/2022]
Abstract
The aim of the present study was to investigate stress gene expression in cultured primary fibroblasts established from Achilles tendons collected during autopsies from sudden infant death syndrome (SIDS) cases, and age-matched controls (infants dying in a traumatic event). Expression of 4 stress responsive genes, HSPA1B, HSPD1, HMOX1, and SOD2, was studied by quantitative reverse transcriptase PCR analysis of RNA purified from cells cultured under standard or various thermal stress conditions. The expression of all 4 genes was highly influenced by thermal stress in both SIDS and control cells. High interpersonal variance found in the SIDS group indicated that they represented a more heterogeneous group than controls. The SIDS group responded to thermal stress with a higher expression of the HSPA1B and HSPD1 genes compared to the control group, whereas no significant difference was observed in the expression of SOD2 and HMOX1 between the two groups. The differences were related to the heat shock treatment as none of the genes were expressed significantly different in SIDS at base levels at 37 °C. SOD2 and HMOX1 were up regulated in both groups, for SOD2 though the expression was lower in SIDS at all time points measured, and may be less related to heat stress. Being found dead in the prone position (a known risk factor for SIDS) was related to a lower HSPA1B up-regulation in SIDS compared to SIDS found on their side or back. The study demonstrates the potential usefulness of gene expression studies using cultured fibroblasts established from deceased individuals as a tool for molecular and pathological investigations in forensic and biomedical sciences.
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Affiliation(s)
- Marianne Cathrine Rohde
- Institute of Forensic Medicine, Department of Forensic Pathology, Aarhus University, Denmark.
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23
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Mansilla MJ, Montalban X, Espejo C. Heat shock protein 70: roles in multiple sclerosis. Mol Med 2012; 18:1018-28. [PMID: 22669475 DOI: 10.2119/molmed.2012.00119] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 05/31/2012] [Indexed: 11/06/2022] Open
Abstract
Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE.
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Affiliation(s)
- María José Mansilla
- Unitat de Neuroimmunologia Clínica, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
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24
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Raynes R, Leckey BD, Nguyen K, Westerheide SD. Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans. J Biol Chem 2012; 287:29045-53. [PMID: 22778258 DOI: 10.1074/jbc.m112.353714] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The heat shock response (HSR) is responsible for maintaining cellular and organismal health through the regulation of proteostasis. Recent data demonstrating that the mammalian HSR is regulated by SIRT1 suggest that this response may be under metabolic control. To test this hypothesis, we have determined the effect of caloric restriction in Caenorhabditis elegans on activation of the HSR and have found a synergistic effect on the induction of hsp70 gene expression. The homolog of mammalian SIRT1 in C. elegans is Sir2.1. Using a mutated C. elegans strain with a sir2.1 deletion, we show that heat shock and caloric restriction cooperate to promote increased survivability and fitness in a sir2.1-dependent manner. Finally, we show that caloric restriction increases the ability of heat shock to preserve movement in a polyglutamine toxicity neurodegenerative disease model and that this effect is dependent on sir2.1.
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Affiliation(s)
- Rachel Raynes
- Department of Cell Biology, Microbiology and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, Florida 33620, USA
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25
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Goloudina AR, Demidov ON, Garrido C. Inhibition of HSP70: a challenging anti-cancer strategy. Cancer Lett 2012; 325:117-24. [PMID: 22750096 DOI: 10.1016/j.canlet.2012.06.003] [Citation(s) in RCA: 165] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 06/11/2012] [Accepted: 06/18/2012] [Indexed: 12/15/2022]
Abstract
HSP70 is a chaperone that accumulates in the cells after many different stresses promoting cell survival in response to the adverse conditions. In contrast to normal cells, most cancer cells abundantly express HSP70 at the basal level to resist to various insults at different stages of tumorigenesis and during anti-cancer treatment. This cancer cells addiction for HSP70 is the rational for its targeting in cancer therapy. Much effort has been dedicated in the last years for the active search of HSP70 inhibitors. Additionally, the recent clinical trials on highly promising inhibitors of another stress protein, HSP90, showed compensatory increase in HSP70 levels and raised the question of necessity to combine HSP90 inhibitors with simultaneous inhibition of HSP70. Here we analyzed the recent advancement in creation of novel HSP70 inhibitors and different strategies for their use in anti-cancer therapy.
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Affiliation(s)
- Anastasia R Goloudina
- Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, University of Burgundy, Dijon, France
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26
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27
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Kiyatkin EA, Sharma HS. Expression of heat shock protein (HSP 72 kDa) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection? J Neural Transm (Vienna) 2011; 118:47-60. [PMID: 20931246 PMCID: PMC3150468 DOI: 10.1007/s00702-010-0477-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Accepted: 08/23/2010] [Indexed: 10/19/2022]
Abstract
In the present study, light and electron microscopy were used to examine heat shock protein (HSP 72 kD) expression during acute methamphetamine (METH) intoxication in rats and evaluate its relationships with brain temperature and alterations in a number of other histochemical and morphological parameters. Freely moving rats received METH at the same dose (9 mg/kg, sc) but at different ambient temperatures (23 and 29°C), showing a wide range of brain temperature elevations (37.6-42.5°C); brains were taken for histochemical and morphological evaluations at peak of brain temperature increase. We found that acute METH intoxication induces massive and wide-spread HSP expression in neural and glial cells examined in detail in the cortex, hippocampus, thalamus, and hypothalamus. In each of these structures, the number of HSP-positive cells tightly correlated with brain temperature elevation. The changes in HSP immunoreactivity were also tightly related to alterations in permeability of the blood-brain barrier, acute glial activation, and brain edema assessed by albumin and GFAP immunoreactivity and measuring tissue water content, respectively. While robust and generalized HSP production normally appears to be the part of an adaptive brain response associated with METH-induced metabolic activation, activation of this protective mechanism has its natural limits and could not counteract the damaging effects of oxidative stress, high temperature, and edema--the leading factors of METH-induced neurotoxicity.
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Affiliation(s)
- Eugene A Kiyatkin
- Behavioral Neuroscience Branch, National Institute on Drug Abuse-Intramural Research Program, NIH, 333 Cassell Drive, Baltimore, MD 21224, USA.
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28
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Abstract
Hyperthermia has been known to induce malformations in numerous animal models as well being associated with human abnormalities. This was apparent particularly when the hyperthermia exposure was during the early stages of neural development. Although it was recognized relatively early that these exposures induced cell death, the specific molecular mechanism of how a brief heat exposure was translated in to specific cellular functions remains largely unknown. While our understanding of the events that govern how cells react to heat, or stresses in general, has increased, there is much that remains undiscovered. In this brief review, animal and clinical observations are outlined as are some of the scientific explorations that were undertaken to characterize, define, and better understand the morphological, biochemical, and molecular effects of hyperthermia on the developing embryo.
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Affiliation(s)
- Gregory D Bennett
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.
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29
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Sharma HS, Muresanu D, Sharma A, Zimmermann-Meinzingen S. Cerebrolysin treatment attenuates heat shock protein overexpression in the brain following heat stress: an experimental study using immunohistochemistry at light and electron microscopy in the rat. Ann N Y Acad Sci 2010; 1199:138-48. [PMID: 20633119 DOI: 10.1111/j.1749-6632.2009.05330.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The possibility that overexpression of heat shock proteins (HSPs) in the CNS represents a neurodestructive signal following hyperthermia was examined in a rat model using a potent neuroprotective drug, Cerebrolysin (Ebewe Pharma, Austria). Rats subjected to four hours of heat stress in a biological oxygen demand incubator at 38 degrees C developed profound hyperthermia (41.23 +/- 0.14 degrees C) and overexpressed HSP 72 kD in several brain regions: cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, brain stem, and spinal cord compared to controls. This HSP overexpression closely correlated with the leakage of blood-brain barrier permeability and vasogenic edema formation in these brain areas. HSP positive cells are largely confined in the edematous brain regions showing Evans blue leakage. Pretreatment with Cerebrolysin (5 mL/kg, i.v.) 30 minutes before heat stress markedly attenuated hyperthermia (39.48 +/- 0.23 degrees C, P < 0.01) and the induction of HSP to all the brain regions examined. Leakage of Evans blue albumin and increase in brain water content in these brain areas are also markedly reduced with Cerebrolysin pretreatment. These results are the first to show that Cerebrolysin, if administered before heat stress, attenuates hyperthermia induced stress reaction and HSP 72 kD induction. Taken together, these novel observations suggest that upregulation of HSP 72 kD in brain represents neurodestructive signals and a reduction in cellular stress mechanisms leading to decline in HSP expression is neuroprotective in nature.
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Affiliation(s)
- Hari Shanker Sharma
- Department of Surgical Sciences, Anaesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, Sweden.
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30
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Yamashima T, Oikawa S. The role of lysosomal rupture in neuronal death. Prog Neurobiol 2009; 89:343-58. [PMID: 19772886 DOI: 10.1016/j.pneurobio.2009.09.003] [Citation(s) in RCA: 142] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2009] [Revised: 09/11/2009] [Accepted: 09/15/2009] [Indexed: 12/19/2022]
Abstract
Apoptosis research in the past two decades has provided an enormous insight into its role in regulating cell death. However, apoptosis is only part of the story, and inhibition of neuronal necrosis may have greater impact than apoptosis, on the treatment of stroke, traumatic brain injury, and neurodegenerative diseases. Since the "calpain-cathepsin hypothesis" was first formulated, the calpain- and cathepsin-mediated regulation of necrotic cascades observed in monkeys, has been demonstrated to be a common neuronal death mechanism occurring from simpler organisms to humans. However, the detailed mechanism inducing lysosomal destabilization still remains poorly understood. Heat-shock protein-70 (Hsp70) is known to stabilize lysosomal membrane and protect cells from oxidative stress and apoptotic stimuli in many cell death pathways. Recent proteomics approach comparing pre- and post-ischemic hippocampal CA1 neurons as well as normal and glaucoma-suffered retina of primates, suggested that the substrate protein upon which activated calpain acts at the lysosomal membrane of neurons might be Hsp70. Understanding the interaction between activated calpains and Hsp70 will help to unravel the mechanism that destabilizes the lysosomal membrane, and will provide new insights into clarifying the whole cascade of neuronal necrosis. Although available evidence is circumferential, it is hypothesized that activated calpain cleaves oxidative stress-induced carbonylated Hsp70.1 (a major human Hsp70) at the lysosomal membrane, which result in lysosomal rupture/permeabilization. This review aims at highlighting the possible mechanism of lysosomal rupture in neuronal death by a modified "calpain-cathepsin hypothesis". As the autophagy-lysosomal degradation pathway is a target of oxidative stress, the implication of autophagy is also discussed.
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Affiliation(s)
- Tetsumori Yamashima
- Department of Restorative Neurosurgery, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8641, Japan.
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CLONING AND EXPRESSION ANALYSIS OF AN INDUCIBLE HEAT SHOCK PROTEIN 70 GENE FROM RED SWAMP CRAYFISH, PRCCAMBARUS CLARKII. ACTA ACUST UNITED AC 2009. [DOI: 10.3724/sp.j.1035.2009.40627] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Lin L, Kragh PM, Purup S, Kuwayama M, Du Y, Zhang X, Yang H, Bolund L, Callesen H, Vajta G. Osmotic stress induced by sodium chloride, sucrose or trehalose improves cryotolerance and developmental competence of porcine oocytes. Reprod Fertil Dev 2009; 21:338-44. [DOI: 10.1071/rd08145] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2008] [Accepted: 09/29/2008] [Indexed: 12/20/2022] Open
Abstract
Exposure of porcine oocytes to increased concentrations of NaCl prior to manipulation has been reported not only to increase cryotolerance after vitrification, but also to improve developmental competence after somatic cell nuclear transfer (SCNT). In the present study we compared the effects of NaCl with those of concentrated solutions of two non-permeable osmotic agents, namely sucrose and trehalose, on the cryotolerance and developmental competence of porcine oocytes. In Experiment 1, porcine in vitro-matured cumulus–oocyte complexes (COCs; n = 1200) were exposed to 588 mOsmol NaCl, sucrose or trehalose solutions for 1 h, allowed to recover for a further 1 h, vitrified, warmed and subjected to parthenogenetic activation. Both Day 2 (where Day 0 is the day of activation) cleavage and Day 7 blastocyst rates were significantly increased after NaCl, sucrose and trehalose osmotic treatments compared with untreated controls (cleavage: 46 ± 5%, 44 ± 7%, 45 ± 4% and 26 ± 6%, respectively; expanded blastocyst rate: 6 ± 1%, 6 ± 2%, 7 ± 2% and 1 ± 1%, respectively). In Experiment 2, COCs (n = 2000) were treated with 588 mOsmol NaCl, sucrose or trehalose, then used as recipients for SCNT (Day 0). Cleavage rates on Day 1 did not differ between the NaCl-, sucrose-, trehalose-treated and the untreated control groups (92 ± 3%, 95 ± 3%, 92 ± 2% and 94 ± 2%, respectively), but blastocyst rates on Day 6 were higher in all treated groups compared with control (64 ± 2%, 69 ± 5%, 65 ± 3% and 47 ± 4%, respectively). Cell numbers of Day 6 blastocysts were higher in the control and NaCl-treated groups compared with the sucrose- and trehalose-treated groups. In conclusion, treatment of porcine oocytes with osmotic stress improved developmental competence after vitrification combined with parthenogenetic activation, as well as after SCNT.
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Allard JS, Heilbronn LK, Smith C, Hunt ND, Ingram DK, Ravussin E, de Cabo R. In vitro cellular adaptations of indicators of longevity in response to treatment with serum collected from humans on calorie restricted diets. PLoS One 2008; 3:e3211. [PMID: 18791640 PMCID: PMC2527659 DOI: 10.1371/journal.pone.0003211] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2008] [Accepted: 08/20/2008] [Indexed: 12/20/2022] Open
Abstract
Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period). Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1alpha mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans.
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Affiliation(s)
- Joanne S. Allard
- Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
| | - Leonie K. Heilbronn
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America
| | - Carolina Smith
- Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
| | - Nicole D. Hunt
- Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
| | - Donald K. Ingram
- Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America
| | - Eric Ravussin
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America
| | | | - Rafael de Cabo
- Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
- * E-mail:
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Gefen R, Eshel G, Abu-Kishk I, Lahat E, Youngster I, Rosenbloom E, Kozer E. Hemorrhagic shock and encephalopathy syndrome: clinical course and neurological outcome. J Child Neurol 2008; 23:589-92. [PMID: 18160555 DOI: 10.1177/0883073807309790] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The syndrome of hemorrhagic shock and encephalopathy is associated with an acute onset of diarrhea, followed by shock, disseminated intravascular coagulopathy, multiorgan failure, and encephalopathy. The etiology of this syndrome is unknown, and despite intensive treatment, the outcome is often fatal or associated with severe neurological sequelae. Two infants aged 6 and 9 months were admitted with this syndrome within a 24-hour time interval. The authors hereby present the clinical course and a prospective evaluation of the neurological outcome. A review of the literature regarding this infrequent syndrome is presented.
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Affiliation(s)
- Roni Gefen
- Pediatric Division, Assaf Harofeh Medical Center, Zerifin 70300, Israel.
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Abstract
Heat stroke is a life-threatening illness that affects all segments of society, including the young, aged, sick, and healthy. The recent high death toll in France (Dorozynski, 2003) and the death of high-profile athletes has increased public awareness of the adverse effects of heat injury. However, the etiology of the long-term consequences of this syndrome remains poorly understood such that preventive/treatment strategies are needed to mitigate its debilitating effects. Cytokines are important modulators of the acute phase response (APR) to stress, infection, and inflammation. Current data implicating cytokines in heat stroke responses are mainly from correlation studies showing elevated plasma levels in heat stroke patients and experimental animal models. Correlation data fall far short of revealing the mechanisms of cytokine actions such that additional research to determine the role of these endogenous substances in the heat stroke syndrome is required. Furthermore, cytokine determinations have occurred mainly at end-stage heat stroke, such that the role of these substances in progression and long-term recovery is poorly understood. Despite several studies implicating cytokines in heat stroke pathophysiology, few studies have examined the protective effect(s) of cytokine antagonism on the morbidity and mortality of heat stroke. This is particularly surprising since heat stroke responses resemble those observed in the endotoxemic syndrome, for which a role for endogenous cytokines has been strongly implicated. The implication of cytokines as mediators of endotoxemia and the presence of circulating endotoxin in heat stroke patients suggests that much knowledge can be gained from applying our current understanding of endotoxemic pathophysiology to the study of heat stroke. Heat shock proteins (HSPs) are highly conserved proteins that function as molecular chaperones for denatured proteins and reciprocally modulate cytokine production in response to stressful stimuli. HSPs have been shown repeatedly to confer protection in heat stroke and injury models. Interactions between HSPs and cytokines have received considerable attention in the literature within the last decade such that a complex pathway of interactions between cytokines, HSPs, and endotoxin is thought to be occurring in vivo in the orchestration of the APR to heat injury. These data suggest that much of the pathophysiologic changes observed with heat stroke are not a consequence of heat exposure, per se, but are representative of interactions among these three (and presumably additional) components of the innate immune response. This chapter will provide an overview of current knowledge regarding cytokine, HSP, and endotoxin interactions in heat stroke pathophysiology. Insight is provided into the potential therapeutic benefit of cytokine neutralization for mitigation of heat stroke morbidity and mortality based on our current understanding of their role in this syndrome.
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Affiliation(s)
- Lisa R Leon
- US Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, MA 01760-5007, USA.
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Obrenovitch TP. Molecular physiology of preconditioning-induced brain tolerance to ischemia. Physiol Rev 2008; 88:211-47. [PMID: 18195087 DOI: 10.1152/physrev.00039.2006] [Citation(s) in RCA: 176] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Ischemic tolerance describes the adaptive biological response of cells and organs that is initiated by preconditioning (i.e., exposure to stressor of mild severity) and the associated period during which their resistance to ischemia is markedly increased. This topic is attracting much attention because preconditioning-induced ischemic tolerance is an effective experimental probe to understand how the brain protects itself. This review is focused on the molecular and related functional changes that are associated with, and may contribute to, brain ischemic tolerance. When the tolerant brain is subjected to ischemia, the resulting insult severity (i.e., residual blood flow, disruption of cellular transmembrane gradients) appears to be the same as in the naive brain, but the ensuing lesion is substantially reduced. This suggests that the adaptive changes in the tolerant brain may be primarily directed against postischemic and delayed processes that contribute to ischemic damage, but adaptive changes that are beneficial during the subsequent test insult cannot be ruled out. It has become clear that multiple effectors contribute to ischemic tolerance, including: 1) activation of fundamental cellular defense mechanisms such as antioxidant systems, heat shock proteins, and cell death/survival determinants; 2) responses at tissue level, especially reduced inflammatory responsiveness; and 3) a shift of the neuronal excitatory/inhibitory balance toward inhibition. Accordingly, an improved knowledge of preconditioning/ischemic tolerance should help us to identify neuroprotective strategies that are similar in nature to combination therapy, hence potentially capable of suppressing the multiple, parallel pathophysiological events that cause ischemic brain damage.
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Affiliation(s)
- Tihomir Paul Obrenovitch
- Division of Pharmacology, School of Life Sciences, University of Bradford, Bradford, United Kingdom.
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Sandström ME, Siegler JC, Lovell RJ, Madden LA, McNaughton L. The effect of 15 consecutive days of heat-exercise acclimation on heat shock protein 70. Cell Stress Chaperones 2008; 13:169-75. [PMID: 18759002 PMCID: PMC2673895 DOI: 10.1007/s12192-008-0022-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2007] [Revised: 10/16/2007] [Accepted: 10/29/2007] [Indexed: 10/22/2022] Open
Abstract
The purpose of this study was to investigate the alterations in serum heat shock protein (Hsp) 70 levels during a 15-consecutive-day intermittent heat-exercise protocol in a 29-year-old male ultra marathon runner. Heat acclimation, for the purpose of physical activities in elevated ambient temperatures, has numerous physiological benefits including mechanisms such as improved cardiac output, increased plasma volume and a decreased core temperature (T (c)). In addition to the central adaptations, the role of Hsp during heat acclimation has received an increasing amount of attention. The acclimation protocol applied was designed to correspond with the athlete's tapering period for the 2007 Marathon Des Sables. The subject (VO(2)max = 50.7 ml.kg(-1).min(-1), peak power output [PPO] = 376 W) cycled daily for 90 min at a workload corresponding to 50% of VO(2)max in a temperature-controlled room (average WBGT = 31.9 +/- 0.9 degrees C). Venous blood was sampled before and after each session for measurement of serum osmolality and serum Hsp70. In addition, T (c), heart rate (HR) and power output (PO) was measured throughout the 90 min to ensure that heat acclimation was achieved during the 15-day period. The results show that the subject was successfully heat acclimated as seen by the lowered HR at rest and during exercise, decreased resting and exercising T (c) and an increased PO. The heat exercise resulted in an initial increase in Hsp70 concentrations, known as thermotolerance, and the increase in Hsp70 after exercise was inversely correlated to the resting values of Hsp70 (Spearman's rank correlation = -0.81, p < 0.01). Furthermore, the 15-day heat-exercise protocol also increased the basal levels of Hsp70, a response different from that of thermotolerance. This is, as far as we are aware, the first report showing Hsp70 levels during consecutive days of intermittent heat exposure giving rise to heat acclimation. In conclusion, a relatively longer heat acclimation protocol is suggested to obtain maximum benefit of heat acclimation inclusive of both cellular and systemic adaptations.
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Affiliation(s)
- Marie E Sandström
- Department of Sport, Health and Exercise Science, University of Hull, Cottingham Road, Hull, UK.
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Ishibashi J, Yamashita K, Ishikawa T, Hosokawa H, Sumida K, Nagayama M, Kitamura S. The effects inhibiting the proliferation of cancer cells by far-infrared radiation (FIR) are controlled by the basal expression level of heat shock protein (HSP) 70A. Med Oncol 2007; 25:229-37. [PMID: 17968683 PMCID: PMC2386844 DOI: 10.1007/s12032-007-9020-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2007] [Accepted: 10/09/2007] [Indexed: 11/28/2022]
Abstract
We developed a tissue culture incubator that can continuously irradiate cells with far-infrared radiation (FIR) of wavelengths between 4 and 20 μm with a peak of 7–12 μm, and found that FIR caused different inhibiting effects to five human cancer cell lines, namely A431 (vulva), HSC3 (tongue), Sa3 (gingiva), A549 (lung), and MCF7 (breast). Then, in order to make clear the control system for the effect of FIR, the gene expression concerned to the inhibition effect by FIR were analyzed. In consequence, basal expression level of HSP70A mRNA was higher in A431 and MCF7 cells than in the FIR-sensitive HSC3, Sa3, and A549 cells. Also, the over expression of HSP70 inhibited FIR-induced growth arrest in HSC3 cells, and an HSP70 siRNA inhibited the proliferation of A431 cells by irradiation with FIR. These results indicate that the effect of a body temperature range of FIR suppressing the proliferation of some cancer cells is controlled by the basal expression level of heat shock protein (HSP) 70A. This finding suggested that FIR should be very effective medical treatment for some cancer cells which have a low level of HSP70. Still more, if the level of HSP70 in any cancer of a patient was measured, the effect of medical treatment by FIR can be foreseen for the cancer.
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Affiliation(s)
- Jun Ishibashi
- Department of Oral and Maxillofacial Anatomy, Medical Science for Oral and Maxillofacial Regeneration, Graduate School of Health Biosciences, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8504, Japan
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Mottola MF, Vanderspank D, Schachter CL, VanHeest J, Tanguay RM. Cellular accumulation of heat shock protein (Hsp) 72i in fetuses of trained rats. Cell Stress Chaperones 2007; 12:101-5. [PMID: 17688188 PMCID: PMC1949329 DOI: 10.1379/csc-223r.1] [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: 11/24/2022] Open
Abstract
Forty-five Sprague-Dawley rats (60-80 days old) were randomly placed into one of three groups: sedentary pregnant control (PC); prepregnancy trained animals that exercised throughout pregnancy (PR); and nonpregnant trained animals (NPR). Each exercising animal ran at approximately 60-70% aerobic capacity (VO2max) for 1 hour/day up to and including day 18 of gestation (term = 21 days). On day 20 of gestation, fetuses were excised from each pregnant animal and scrutinized for gross abnormalities. In 3 randomly chosen fetuses from each litter, brain, heart, kidney, hind limb, and placental tissues were removed to assess the accumulation of the inducible isoform of the 70-kilodalton heat shock protein (Hsp 72i). No significant differences were detected between fetal hearts, hind limbs, or placental tissues of PC or PR groups. No Hsp 72i signal could be detected in fetal kidney or brain tissues from either pregnant group. Results indicate that maternal core temperature did not reach the threshold that would induce either gross fetal abnormalities or a fetal heat shock protein response. However, fetal and placental growth was reduced by the exercise protocol.
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Affiliation(s)
- Michelle F Mottola
- School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, ON N6A 3K7, Canada.
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Hagiwara S, Iwasaka H, Matsumoto S, Noguchi T, Yoshioka H. Association between heat stress protein 70 induction and decreased pulmonary fibrosis in an animal model of acute lung injury. Lung 2007; 185:287-293. [PMID: 17629797 DOI: 10.1007/s00408-007-9018-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2007] [Accepted: 06/03/2007] [Indexed: 10/23/2022]
Abstract
The hyperthermia-induced activation of the stress protein response allows cells to withstand metabolic insults that would otherwise be lethal. This phenomenon is referred to as thermotolerance. Heat shock protein 70 (HSP70) has been shown to play an important role in this hyperthermia-related cell protection. HSP70 confers protection against cellular and tissue injury. Our objective was to determine the effect of heat stress on the histopathology of pulmonary fibrosis caused by the administration of lipopolysaccharide (LPS) in Wistar rats. The rats were randomly divided into three groups. In the control group, rats were heated to 42 degrees C for 15 min. In the LPS group, rats were given LPS in 0.9% NaCl solution (10 mg/kg body weight). In the WH (whole-body hyperthermia) +LPS group, rats were heated to 42 degrees C for 15 min, and 48 h later they were injected with LPS dissolved in a 0.9% NaCl solution (10 mg/kg body weight). We investigated lung histopathology and performed a Northern blot analysis daily. Hyperthermia was shown to reduce tissue injury caused by the administration of LPS. Pulmonary tissue HSP70 mRNA was found to be elevated at 3 h after heating. HSP70 protein levels in the serum increased after whole-body hyperthermia. However, neither the expression of HSP47 mRNA nor the expression of type I or type III collagen mRNA was induced by the administration of LPS after whole-body hyperthermia. These data indicate that thermal pretreatment is associated with the induction of HSP70 protein synthesis, which subsequently attenuates tissue damage in experimental lung fibrosis.
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Affiliation(s)
- Satoshi Hagiwara
- Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan.
| | - Hideo Iwasaka
- Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan
| | - Shigekiyo Matsumoto
- Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan
| | - Takayuki Noguchi
- Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan
| | - Hidekatsu Yoshioka
- Department of Anatomy, Biology and Medicine, Biochemistry, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan
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Escobedo I, Peraile I, Orio L, Colado MI, O'Shea E. Evidence for a role of Hsp70 in the neuroprotection induced by heat shock pre-treatment against 3,4-methylenedioxymethamphetamine toxicity in rat brain. J Neurochem 2007; 101:1272-83. [PMID: 17328712 DOI: 10.1111/j.1471-4159.2007.04459.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') produces acute hyperthermia which increases the severity of the selective serotoninergic neurotoxicity produced by the drug in rats. Heat shock protein 70 (Hsp70) is a major inducible cellular protein expressed in stress conditions and which is thought to exert protective functions. MDMA (12.5 mg/kg, i.p.), given to rats housed at 22 degrees C, produced an immediate hyperthermia and increased Hsp70 in frontal cortex between 3 h and 7 days after administration. MDMA, given to rats housed at low ambient temperature (4 degrees C) produced transient hypothermia followed by mild hyperthermia but no increase in Hsp70 expression, while rats treated at elevated room temperature (30 degrees C) showed enhanced hyperthermia and similar expression of Hsp70 to that seen in rats housed at 22 degrees C. Fluoxetine-induced inhibition of 5-HT release and hydroxyl radical formation did not modify MDMA-induced Hsp70 expression 3 h later. Four- or 8-day heat shock (elevation of basal rectal temperature by 1.5 degrees C for 1 h) or geldanamycin pre-treatment induced Hsp70 expression and protected against MDMA-induced serotoninergic neurotoxicity without affecting drug-induced hyperthermia. Thus, MDMA-induced Hsp70 expression depends on the drug-induced hyperthermic response and not on 5-HT release or hydroxyl radical formation and pre-induction of Hsp70 protects against the long-term serotoninergic damage produced by MDMA.
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Affiliation(s)
- Isabel Escobedo
- Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
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42
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Daugaard M, Rohde M, Jäättelä M. The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett 2007; 581:3702-10. [PMID: 17544402 DOI: 10.1016/j.febslet.2007.05.039] [Citation(s) in RCA: 820] [Impact Index Per Article: 45.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2007] [Revised: 05/14/2007] [Accepted: 05/14/2007] [Indexed: 12/12/2022]
Abstract
The human heat shock protein 70 (Hsp70) family contains at least eight homologous chaperone proteins. Endoplasmatic reticulum and mitochondria have their specific Hsp70 proteins, whereas the remaining six family members reside mainly in the cytosol and nucleus. The requirement for multiple highly homologous although different Hsp70 proteins is still far from clear, but their individual and tissue-specific expression suggests that they are assigned distinct biological tasks. This concept is supported by the fact that mice knockout for different Hsp70 genes display remarkably discrete phenotypes. Moreover, emerging data suggest that individual Hsp70 proteins can bring about non-overlapping and chaperone-independent functions essential for growth and survival of cancer cells. This review summarizes our present knowledge of the individual members of human Hsp70 family and elaborate on the functional differences between the cytosolic/nuclear representatives.
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Affiliation(s)
- Mads Daugaard
- Apoptosis Department and Centre for Genotoxic Stress Response, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
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Bayerl C, Jung EG. Microinjection of an antibody against HSP 72 in keratinocytes to study acute UV injury⊃. Exp Dermatol 2007. [DOI: 10.1111/j.1600-0625.1999.tb00378.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Villalobos ARA, Renfro JL. Trimethylamine oxide suppresses stress-induced alteration of organic anion transport in choroid plexus. J Exp Biol 2007; 210:541-52. [PMID: 17234624 DOI: 10.1242/jeb.02681] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
SUMMARYThe effect of physicochemical stress on organic anion transport across the vertebrate blood–cerebrospinal fluid (CSF) barrier in the presence and absence of an endogenous cytoprotectant, trimethylamine oxide (TMAO), was investigated in isolated IVth choroid plexus (CP) of spiny dogfish shark(Squalus acanthias), an animal with naturally high levels of TMAO(∼70 mmol l–1). Active transepithelial absorption of the organic anion, 2,4-dichlorophenoxyacetic acid (2,4-D), by IVth CP mounted in Ussing chambers was measured after in vitro stress, and a marker for the cellular stress response, inducible heat shock protein 70 (Hsp70), was assayed by immunoblot analysis. Transient heat stress (a shift from the normal 13.5°C to 23.5°C for 1 h) decreased 2,4-D transport by ∼66%;however, the same stress minus TMAO (isosmotic replacement with urea) had no effect on transport rate. In the absence of TMAO, stress-induced Hsp70 accumulation was more than double that seen in the presence of TMAO. Likewise,exposure to 50 μmol l–1 Zn for 6 h induced a twofold greater Hsp70 accumulation in the absence of TMAO than in its presence, and the higher Hsp70 level was associated with a higher 2,4-D transport rate. Heat stress and 50 μmol l–1 Zn also induced more pronounced increases in Hsp70 mRNA in the absence of TMAO. Thus, the cellular stress response can significantly alter CP organic anion transport capacity, and an endogenous osmolyte can suppress that response.
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Affiliation(s)
- Alice R A Villalobos
- Center for Membrane Toxicological Studies, Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672, USA.
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45
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Wheeler DS, Wong HR. Heat shock response and acute lung injury. Free Radic Biol Med 2007; 42:1-14. [PMID: 17157189 PMCID: PMC1790871 DOI: 10.1016/j.freeradbiomed.2006.08.028] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2006] [Revised: 08/23/2006] [Accepted: 08/29/2006] [Indexed: 11/19/2022]
Abstract
All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e., exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury.
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Affiliation(s)
- Derek S. Wheeler
- Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center; Kindervelt Laboratory for Critical Care Medicine Research, Children’s Hospital Research Foundation;]Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Hector R. Wong
- Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center; Kindervelt Laboratory for Critical Care Medicine Research, Children’s Hospital Research Foundation;]Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
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47
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Khazzaka A, Figwer P, Poirel M, Serrar M, Franck M. Hsp70 response in pigs is affected by their Halothane genotypes after heat stress. J Therm Biol 2006. [DOI: 10.1016/j.jtherbio.2006.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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Feng X, Bonni S, Riabowol K. HSP70 induction by ING proteins sensitizes cells to tumor necrosis factor alpha receptor-mediated apoptosis. Mol Cell Biol 2006; 26:9244-55. [PMID: 17030616 PMCID: PMC1698524 DOI: 10.1128/mcb.01538-06] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
ING proteins affect apoptosis, growth, and DNA repair by transducing stress signals such as DNA damage, binding histones, and subsequently regulating chromatin structure and p53 activity. p53 target genes, including the p21 cyclin-dependent kinase inhibitor and Bax, an inducer of apoptosis, are regulated by ING proteins. To identify additional targets downstream of p33ING1 and p32ING2, cDNA microarrays were performed on phenotypically normal human primary fibroblasts. The 0.36% of genes affected by ING proteins in primary fibroblasts were distinct from targets seen in established cells and included the HSP70 heat shock gene, whose promoter was specifically induced >10-fold. ING1-induced expression of HSP70 shifted cells from survival to a death pathway in response to tumor necrosis factor alpha (TNF-alpha), and p33ING1b protein showed synergy with TNF-alpha in inducing apoptosis, which correlated with reduced NF-kappaB-dependent transcription. These findings are consistent with previous reports that HSP70 promotes TNF-alpha-mediated apoptosis by binding I-kappaBeta kinase gamma and impairing NF-kappaB survival signaling. Induction of HSP70 required the amino terminus of ING1b but not the plant homeodomain region that was recently identified as a histone binding domain. Regulation of HSP70 gene expression by the ING tumor suppressors provides a novel link between the INGs and the stress-regulated NF-kappaB survival pathway important in hypoxia and angiogenesis.
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Affiliation(s)
- Xiaolan Feng
- Southern Alberta Cancer Research Institute, Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1
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49
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Wang X, Xu C, Wang X, Wang D, Wang Q, Zhang B. Heat shock response and mammal adaptation to high elevation (hypoxia). ACTA ACUST UNITED AC 2006; 49:500-12. [PMID: 17172058 DOI: 10.1007/s11427-006-2027-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
The mammal's high elevation (hypoxia) adaptation was studied by using the immunological and the molecular biological methods to understand the significance of Hsp (hypoxia) adaptation in the organic high elevation, through the mammal heat shock response. (1) From high elevation to low elevation (natural hypoxia): Western blot and conventional RT-PCR and real-time fluorescence quota PCR were adopted. Expression difference of heat shock protein of 70 (Hsp70) and natural expression of brain tissue of Hsp70 gene was determined in the cardiac muscle tissue among the different elevation mammals (yak). (2) From low elevation to high elevation (hypoxia induction): The mammals (domestic rabbits) from the low elevation were sent directly to the areas with different high elevations like 2300, 3300 and 5000 m above sea level to be raised for a period of 3 weeks before being slaughtered and the genetic inductive expression of the brain tissue of Hsp70 was determined with RT-PCR. The result indicated that all of the mammals at different elevations possessed their heat shock response gene. Hsp70 of the high elevation mammal rose abruptly under stress and might be induced to come into being by high elevation (hypoxia). The speedy synthesis of Hsp70 in the process of heat shock response is suitable to maintain the cells' normal physiological functions under stress. The Hsp70 has its threshold value. The altitude of 5000 m above sea level is the best condition for the heat shock response, and it starts to reduce when the altitude is over 6000 m above sea level. The Hsp70 production quantity and the cell hypoxia bearing capacity have their direct ratio.
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Affiliation(s)
- Xiaolin Wang
- Northwest Plateau Biological Research Institute, Chinese Academy of Sciences, Xining 810001, China.
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Lee WC, Wen HC, Chang CP, Chen MY, Lin MT. Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke. J Appl Physiol (1985) 2006; 100:2073-82. [PMID: 16627676 DOI: 10.1152/japplphysiol.01433.2005] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
This study extends our earlier studies in rats by applying our heatstroke model to a new species. Additionally, transgenic mice are used to examine the role of heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate controls ([−]HSP72), and normal Institute of Cancer Research strain mice (ICR) under pentobarbital sodium anesthesia were subjected to heat stress (40°C) to induce heatstroke. In [−]HSP72 or ICR, the values for mean arterial pressure, the striatal blood flow, and the striatal Po2after the onset of heatstroke were significantly lower than those in preheat controls. The core and brain temperatures, the extracellular concentrations of ischemic and injury markers in the striatum, and the striatal neuronal damage scores were significantly greater than those in the preheat controls. In [−]HSP72 or ICR, the body temperatures, cell ischemia content, and injury marker in the striatum were significantly higher, and the mean arterial pressure, striatal blood flow, and striatal Po2concentration were significantly lower during heatstroke than in [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72 significantly exceeded those of [−]HSP72 or ICR. These results demonstrate that the overexpression of HSP72 in multiple organs improves survival during heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and damage in mice.
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Affiliation(s)
- W C Lee
- Division of Biotechnology, Animal Technology Institute Taiwan, Miaoli, Taiwan
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