title: Heat shock protein 90/Akt pathway participates in the cardioprotective effect of exogenous hydrogen sulfide against high glucose-induced injury to H9c2 cells.
abstract: It has been reported that exogenous hydrogen sulfide (H2S) protects against high glucose (HG)-induced cardiac injury and has a modulatory effect on heat shock protein (HSP) and Akt, which play a cardioprotective role. In this study, we examined whether the HSP90/Akt pathway contributes to the protective effects of exogenous H2S against HG-induced injury to H9c2 cardiac cells. Our results revealed that the exposure of H9c2 cardiac cells to 35 mM glucose (HG) for 1 to 24 h decreased the expression of HSP90 and markedly reduced the expression level of phosphorylated (p)-Akt in a time-dependent manner. Co-exposure of the cells to HG and geldanamycin (GA; an inhibitor of HSP90) aggravated the inhibition of the p-Akt expression level by HG. Of note, treatment of the cells with 400 µM NaHS (a donor of H2S) for 30 min prior to exposure to HG significantly attenuated the HG-induced decrease in the expression levels of both HSP90 and p-Akt, along with inhibition of HG-induced cell injury, as indicated by the increase in cell viability and superoxide dismutase (SOD) activity, and by a decrease in the number of apoptotic cells, reactive oxygen species (ROS) generation, as well as by the decreased dissipation of mitochondrial membrance potential (MMP). Importantly, treatment of the cells with GA or LY294002 (an inhibitor of Akt) prior to exposure to NaHS and HG considerably blocked the cardioprotective effects of NaHS against the HG-induced injury mentioned above. On the whole, the findings of this study demonstrate that the inhibition of the HSP90/Akt pathway may be an important mechanism responsible for HG-induced cardiomyocyte injury. We also provide novel evidence that exogenous H2S protects H9c2 cells against HG-induced injury by activating the HSP90/Akt pathway.
authors.affiliation: Department of Cardiology, Shenzhen Sun Yat-sen Cardiovascular Hospital, Shenzhen, Guangdong, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ke
authors.affiliation: Department of Cardiovascular Medicine and Dongguan Cardiovascular Institute, The Third People's Hospital of Dongguan City, Dongguan, Guangdong, P.R. China.
authors.forename: Jingfu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Longyun
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Cardiovasology and Cardiac Care Unit (CCU), Huangpu Division of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cardiovasology and Cardiac Care Unit (CCU), Huangpu Division of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Anesthesiology, Huangpu Division of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Liqiu
authors.initials: L
authors.lastname: Mo
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ruixian
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Huangpu Division of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Chengheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen Universtity, Guangzhou, Guangdong, P.R. China.
authors.forename: Ruqiong
authors.initials: R
authors.lastname: Nie
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D005947:Glucose / Q000009:adverse effects* / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D002867:Chromones; D018841:HSP90 Heat-Shock Proteins; D009025:Morpholines; D017382:Reactive Oxygen Species; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D006862:Hydrogen Sulfide