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Heat shock protein 90 mediates cytoprotection by H.
- Source :
- Clinical & Experimental Pharmacology & Physiology; Jan2011, Vol. 38 Issue 1, p42-49, 8p, 5 Graphs
- Publication Year :
- 2011
-
Abstract
- 1. Increasing evidence indicates that hydrogen sulphide (HS) 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 HS against chemical hypoxia-induced injury in PC12 cells is not known. 2. In the present study, CoCl (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 HS 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 HS donor, for 3 h prior to exposure to 600 μmol/L CoCl provided significant, concentration-dependant protection to PC12 cells against CoCl-induced cytotoxicity. Specifically, pretreatment of PC12 cells with 400 μmol/L NaHS decreased apoptosis to 16.77 ± 1.77% and blocked the CoCl-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 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 HS-induced neuroprotection against chemical hypoxia-induced injury via anti-oxidant and anti-apoptotic effects. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03051870
- Volume :
- 38
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Pharmacology & Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 56630041
- Full Text :
- https://doi.org/10.1111/j.1440-1681.2010.05462.x