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

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文摘 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 thymoma 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 demonstrated 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
来源 Neural Regeneration Research ,2010,5(22):1706-1711 【核心库】
DOI 10.3969/j.issn.1673-5374. 2010.22.004
关键词 ATP-sensitive potassium channel ; PC12 cells ; hypoxia ; apoptosis ; pinacidil ; phosphatidylinositol-3 kinase/v-akt murine thymoma viral oncogene homolog ; Bcl-2
地址

Department of Neurology, the Affiliated Shengjing Hospital of China Medical University, Liaoning, Shenyang, 110004

语种 英文
文献类型 研究性论文
ISSN 1673-5374
学科 神经病学与精神病学
基金 辽宁省自然科学基金
文献收藏号 CSCD:4095098

参考文献 共 26 共2页

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