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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
Alternative TitleAdenosine triphosphate-sensitive potassium channel opener protects PC12 cells against hypoxia-induced apoptosis through PI3K/Akt and Bcl-2 signaling pathways
Zhang Hong; Jia Chunhong; Zhao Danyang; Lu Yang; Wang Runling; Li Jia
2010
Source PublicationNEURAL REGENERATION RESEARCH
ISSN1673-5374
Volume5Issue:22Pages:1706-1711
AbstractAlthough 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.
Other AbstractAlthough 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
KeywordBRAIN ISCHEMIA AKT NEUROPROTECTION EXPRESSION SURVIVAL DEATH ATP-sensitive potassium channel PC12 cells hypoxia apoptosis pinacidil phosphatidylinositol-3 kinase/v-akt murine thymoma viral oncogene homolog Bcl-2
Indexed ByCSCD
Language英语
Funding Project[Natural Science Foundation of Liaoning Province]
CSCD IDCSCD:4095098
Citation statistics
Document Type期刊论文
Identifierhttp://ir.imr.ac.cn/handle/321006/149367
Collection中国科学院金属研究所
Affiliation中国科学院金属研究所
Recommended Citation
GB/T 7714
Zhang Hong,Jia Chunhong,Zhao Danyang,et al. Adenosine triphosphate-sensitive potassium channel opener protects PC12 cells against hypoxia-induced apoptosis through PI3K/Akt and Bcl-2 signaling pathways[J]. NEURAL REGENERATION RESEARCH,2010,5(22):1706-1711.
APA Zhang Hong,Jia Chunhong,Zhao Danyang,Lu Yang,Wang Runling,&Li Jia.(2010).Adenosine triphosphate-sensitive potassium channel opener protects PC12 cells against hypoxia-induced apoptosis through PI3K/Akt and Bcl-2 signaling pathways.NEURAL REGENERATION RESEARCH,5(22),1706-1711.
MLA Zhang Hong,et al."Adenosine triphosphate-sensitive potassium channel opener protects PC12 cells against hypoxia-induced apoptosis through PI3K/Akt and Bcl-2 signaling pathways".NEURAL REGENERATION RESEARCH 5.22(2010):1706-1711.
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