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Heat shock protein 90 mediates cytoprotection by H 2 S against chemical hypoxia‐induced injury in PC12 cells
Author(s) -
Meng JinLan,
Mei WeiYi,
Dong YanFen,
Wang JianHong,
Zhao ChunMei,
Lan AiPing,
Yang ChunTao,
Chen PeiXi,
Feng JianQiang,
Hu ChenHeng
Publication year - 2011
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05462.x
Subject(s) - cytoprotection , chemistry , hypoxia (environmental) , heat shock protein , apoptosis , reactive oxygen species , hsp90 , downregulation and upregulation , pharmacology , hsp70 , oxygen , biochemistry , microbiology and biotechnology , medicine , biology , organic chemistry , gene
Summary 1. Increasing evidence indicates that hydrogen sulphide (H 2 S) may serve as an important biological cytoprotective agent. Heat shock protein (Hsp) 90 can attenuate stress‐induced injury. However, whether Hsp90 mediates the cytoprotective effect of H 2 S against chemical hypoxia‐induced injury in PC12 cells is not known. 2. In the present study, CoCl 2 (a chemical hypoxia mimetic) was used to treat PC12 cells to create a model of chemical hypoxia. To explore the role of Hsp90 in the cytoprotection afforded by H 2 S against chemical hypoxia‐induced injury, 2 μmol/L 17‐allylaminogeldanamycin (17‐AAG), a selective inhibitor of Hsp90, was administered for 30 min prior to preconditioning with 400 μmol/L NaHS, followed by chemical hypoxia. 3. Cobalt chloride reduced cell viability (by 52.7 ± 1.5%), increased PC12 cell apoptosis (by 42.1 ± 1.5%), induced reactive oxygen species (ROS) by 3.79% compared with control and induced the dissipation of mitochondrial membrane potential (MMP) by 2.56% compared with control. 4. Pretreatment of PC12 cells with 100–400 μmol/L sodium hydrosulphide (NaHS), an H 2 S donor, for 3 h prior to exposure to 600 μmol/L CoCl 2 provided significant, concentration‐dependant protection to PC12 cells against CoCl 2 ‐induced cytotoxicity. Specifically, pretreatment of PC12 cells with 400 μmol/L NaHS decreased apoptosis to 16.77 ± 1.77% and blocked the CoCl 2 ‐induced increase in ROS production and loss of MMP. 5. At 400 μmol/L, NaHS upregulated Hsp90 in a time‐dependant manner (over the period 0–180 min). In addition to its effects on Hsp90 expression, NaHS pretreatment of PC12 cells augmented the overexpression of Hsp90 induced by 600 μmol/L CoCl 2 by 1.38‐fold ( P < 0.01). 6. Treatment of PC12 cells with 2 μmol/L 17‐AAG for 30 min prior to NaHS pretreatment blocked the overexpression of Hsp90 induced by NaHS preconditioning, as evidenced by decreased cell viability (by 54.2 + 1.2%; P < 0.01), increased PC12 cell apoptosis (by 36.6 ± 1.2%; P < 0.01) and increasing ROS production. 7. The findings of the present study provide novel evidence that Hsp90 mediates H 2 S‐induced neuroprotection against chemical hypoxia‐induced injury via anti‐oxidant and anti‐apoptotic effects.