title: Diazoxide preconditioning alleviates caspase-dependent and caspase-independent apoptosis induced by anoxia-reoxygenation of PC12 cells.
abstract: 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.
authors.affiliation: Department of Neurology, the Affiliated Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China. zhangh.7211@163.com
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Danyang
authors.initials: D
authors.lastname: Zhao
authors.forename: Zhanqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Dongming
authors.initials: D
authors.lastname: Zheng
mesh_terms: 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*
chemical_list: D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D020169:Caspases; D005947:Glucose; D003981:Diazoxide; D010100:Oxygen