Diazoxide preconditioning alleviates caspase-dependent and caspase-independent apoptosis induced by anoxia-reoxygenation of PC12 cells.
Although there is increasing evidence that the ATP sensitive potassium channel (K(ATP)) 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 K(ATP) 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 (mitoK(ATP)) 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 mitoK(ATP) 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 mitoK(ATP) channel elicits protective effects against OGD-induced cell apoptosis by caspase-dependent and -independent mitochondrial pathways.
Zhang
Hong
H
Department of Neurology, the Affiliated Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China. zhangh.7211@163.com
Zhao
Danyang
D
Wang
Zhanqiang
Z
Zheng
Dongming
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival; D003981:Diazoxide / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D020169:Caspases; D005947:Glucose; D003981:Diazoxide; D010100:Oxygen