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

作者：Zhang, Hong^*; Jia, Chunhong; Zhao, Danyang; Lu, Yang; Wang, Runling; Li, Jia

来源：Neural Regeneration Research, 2010, 5(22): 1706-1711.

DOI：10.3969/j.issn.1673-5374.2010.22.004

• ATP-sensitive potassium channel
• PC12 cells
• hypoxia
• apoptosis
• pinacidil
• phosphatidylinositol-3 kinase/v-akt murine thymoma viral oncogene homolog
• Bcl-2

Although previous studies have shown the neuroprotective effects of the adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channel opener against ischemic neuronal damage, little is known about the mechanisms involved. Phosphatidylinositol-3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt) and Bcl-2 are thought to be important factors that mediate neuroprotection. The present study investigated the effects of K-ATP openers on hypoxia-induced PC12 cell apoptosis, as well as mRNA and protein expression of Akt and Bcl-2. Results demonstrated that pretreatment of PC12 cells with pinacidil, a K-ATP 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 phosphorylated 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 K-ATP blocker. These results demonstrate for the first time that the protective mechanisms of K-ATP 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.

• 出版日期2010-11-30
• 单位中国医科大学