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

• Published in: Neural regeneration research Vol. 5; no. 22; pp. 1706 - 1711
• Main Author: Hong Zhang Chunhong Jia Danyang Zhao Yang Lu Runling Wang Jia Li
• Format: Journal Article
• Language: English
• Published: Department of Neurology, the Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China 30.11.2010
• Subjects: PC12细胞; 三磷酸腺苷; 信号转导通路; 敏感性; 细胞凋亡; 钾通道; Bcl-2; hypoxia; pinacidil; phosphatidylinositol-3 kinase/v-akt murine thymoma viral oncogene homolog; apoptosis; PC12 cells; ATP-sensitive potassium channel
• ISSN: 1673-5374
• DOI: 10.3969/j.issn.1673-5374.2010.22.004

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 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 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.