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The Journal of Biochemistry
Year: 2010  |  Volume: 148  |  Issue: 4  |  Page No.: 413 - 421

Diazoxide preconditioning alleviates caspase-dependent and caspase-independent apoptosis induced by anoxia-reoxygenation of PC12 cells

H Zhang, D Zhao, Z Wang and D. Zheng    

Abstract:

Although there is increasing evidence that the ATP sensitive potassium channel (KATP) opener exhibits neuroprotective effects against ischaemic neural damage, little is known about the mechanism. Mitochondria play a key role in apoptosis by releasing many important factors, including cytochrome c and apoptosis-inducing factor, which in turn initiate the caspase-dependent and -independent mitochondrial pathway, respectively. In the present study, we sought to determine the locus that KATP opener uses to mediate this protection in PC12 cells. We found that pre-treatment of PC12 cells with diazoxide (DZX), a mitochondrial ATP sensitive potassium channel (mitoKATP) opener, dose-dependently increased cell viability under conditions of oxygen glucose deprivation (OGD). The protective effect of this pre-conditioning was attenuated by 5-hydroxydecanoic acid, a selective mitoKATP blocker. The results showed that DZX inhibits the release of cytochrome c, the activation of caspase-3 and the release of AIF evoked by OGD. Taken together, our results demonstrate for the first time that activation of the mitoKATP channel elicits protective effects against OGD-induced cell apoptosis by caspase-dependent and -independent mitochondrial pathways.

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