Adenosine triphosphate-sensitive potassium channel opener protects PC12 cells against hypoxia-induced apoptosis through PI3K/Akt and Bcl-2 signaling pathways

Although previous studies have shown the neuroprotective effects of the adenosine triphosphate(ATP)-sensitive potassium(KATP) channel opener against ischemic neuronal damage,little is known about the mechanisms involved.Phosphatidylinositol-3 kinase(PI3K)/v-akt murine thy-moma viral oncogene homolog(Akt) and Bcl-2 are thought to be important factors that mediate neuroprotection.The present study investigated the effects of KATP openers on hypoxia-induced PC12 cell apoptosis,as well as mRNA and protein expression of Akt and Bcl-2.Results demon-strated that pretreatment of PC12 cells with pinacidil,a KATP opener,resulted in decreased PC12 cell apoptosis following hypoxia,as detected by Annexin-V fluorescein isothiocyanate/propidium iodide double staining flow cytometry.In addition,mRNA and protein expression of phosphory-lated Akt(p-Akt) and Bcl-2 increased,as detected by immunofluorescence,Western blot analysis,and reverse-transcription polymerase chain reaction.The protective effect of this preconditioning was attenuated by glipizide,a selective KATP blocker.These results demonstrate for the first time that the protective mechanisms of KATP openers on PC12 cell apoptosis following hypoxia could result from activation of the PI3K/Akt signaling pathway,which further activates expression of the downstream Bcl-2 gene.