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|Title:||Hydrogen sulfide protects neurons against hypoxic injury via stimulation of ATP-sensitive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein90 pathway|
|Keywords:||ATP-sensitive potassium channels|
Heat shock protein
Protein kinase C
|Source:||Tay, A.S., Hu, L.F., Lu, M., Wong, P.T.H., Bian, J.S. (2010). Hydrogen sulfide protects neurons against hypoxic injury via stimulation of ATP-sensitive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein90 pathway. Neuroscience 167 (2) : 277-286. ScholarBank@NUS Repository. https://doi.org/10.1016/j.neuroscience.2010.02.006|
|Abstract:||Cerebral hypoxia is one of the main causes of cerebral injury. This study was conducted to investigate the potential protective effect of H2S in in vitro hypoxic models by subjecting SH-SY5Y cells to either oxygen-glucose deprivation or Na2S2O4 (an oxygen scavenger) treatment. We found that treatment with NaHS (an H2S donor, 10-100 μM) 15 min prior to hypoxia increased cell viability in a concentration-dependent manner. Time-course study showed that NaHS was able to exert its protective effect even when added 8 h before or less than 4 h after hypoxia induction. Interestingly, endogenous H2S level was markedly reduced by hypoxia induction. Over-expression of cystathionine-β-synthase prevented hypoxia induced cell apoptosis. Blockade of ATP-sensitive K+ (KATP) channels with glibenclamide and HMR-1098, protein kinase C (PKC) with its three specific inhibitors (chelerythrine, bisindolylmaleide I and calphostin C), extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059 and heat shock protein 90 (Hsp90) with geldanamycin and radicicol significantly attenuated the protective effects of NaHS. Western blots showed that NaHS significantly stimulated ERK1/2 activation and Hsp90 expression. In conclusion, H2S exerts a protective effect against cerebral hypoxia induced neuronal cell death via KATP/PKC/ERK1/2/Hsp90 pathway. Our findings emphasize the important neuroprotective role of H2S in the brain during cerebral hypoxia. © 2010 IBRO.|
|Appears in Collections:||Staff Publications|
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