title: Novel insights into the role of HSP90 in cytoprotection of H2S against chemical hypoxia-induced injury in H9c2 cardiac myocytes.
abstract: The present study evaluated potential mechanisms of hydrogen sulfide (H2S)-mediated cardioprotection using an in vitro chemical hypoxia-induced injury model. We have demonstrated that H2S protects H9c2 cardiomyoblasts (H9c2) against chemical hypoxia-induced injuries by suppressing oxidative stress and preserving mitochondrial function. The aim of this study was to investigate the role of heat shock protein 90 (HSP90) in cardioprotection of H2S in H9c2 cells. The findings of the present study showed that cobalt chloride (CoCl2), a chemical hypoxia agent, significantly enhanced the expression of HSP90 and that 17-allylamino-17-demethoxy geldanamycin (17-AAG), a selective inhibitor of HSP90, aggravated concentration-dependent cytotoxicity induced by CoCl2. Exogenous administration of NaHS (a donor of H2S) augmented not only HSP90 expression under normal conditions, but also CoCl2-induced overexpression of HSP90. Pre-treatment with 17-AAG significantly blocked the cardioprotection of H2S against CoCl2-induced injuries, leading to increases in cytotoxicity and apoptotic cells. Furthermore, pre-treatment with 17-AAG also antagonized the inhibitory effects of NaHS on overproduction of reactive oxygen species (ROS), a loss of mitochondrial membrane potential (MMP) and ATP depletion induced by CoCl2. In conclusion, these results demonstrate that the increased expression of HSP90 may be one of the endogenous defensive mechanisms for resisting chemical hypoxia-induced injury in H9c2 cells. We also provide novel evidence that HSP90 mediates the cardioprotection of H2S against CoCl2-induced injuries by its antioxidant effect and preservation of mitochondrial function in H9c2 cells.
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China.
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Yang
authors.forename: Chuntao
authors.initials: C
authors.lastname: Yang
authors.forename: Liangcan
authors.initials: L
authors.lastname: Xiao
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liao
authors.forename: Aiping
authors.initials: A
authors.lastname: Lan
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Wang
authors.forename: Ruixian
authors.initials: R
authors.lastname: Guo
authors.forename: Peixi
authors.initials: P
authors.lastname: Chen
authors.forename: Chengheng
authors.initials: C
authors.lastname: Hu
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Feng
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000378:metabolism; D015153:Blotting, Western; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D047029:Lactams, Macrocyclic / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D017382:Reactive Oxygen Species; D003035:Cobalt; C112765:tanespimycin; D000255:Adenosine Triphosphate; C018021:cobaltous chloride; D006862:Hydrogen Sulfide