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M3受体通过激活MEK1/2-ERK1/2信号通路促进H9c2心肌细胞生存 被引量：2

M3 muscarinic acetylcholine receptors promote the survival of H9c2 cardiomyocytes through activating MEK1/2-ERK1/2 signaling pathway
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摘要 目的研究毒蕈碱型胆碱受体(M受体)对H9c2心肌细胞MEK1/2-ERK1/2信号通路的调控作用及其对细胞活力的影响。方法 H9c2心肌细胞用非选择性或选择性M受体拮抗药处理30 min之后,以氨甲酰胆碱刺激细胞,然后用Western Blot检测全细胞蛋白质中MEK1/2和ERK1/2磷酸化水平的变化,采用Alamar Blue法检测细胞活力。结果以氨甲酰胆碱刺激H9c2心肌细胞能显著增加MEK1/2和ERK1/2的磷酸化水平,这种活化作用可被非选择性M受体拮抗药阿托品完全阻断;M3受体选择性拮抗药DAU 5884可以阻断氨甲酰胆碱对MEK1/2-ERK1/2的激活,但M1、M2和M4受体的选择性拮抗药则没有这种阻断作用;在无血清的培养基中,氨甲酰胆碱能增加H9c2心肌细胞的生存能力,这种细胞保护作用可被阿托品和DAU 5884消除。结论在H9c2心肌细胞中,氨甲酰胆碱通过M3受体调控MEK1/2-ERK1/2信号通路,并由此促进细胞的生存。 Objective To determine the effect of muscarinic acetylcholine receptor（M-receptor） stimulation on the activation of MEK1/2-ERK1/2 signaling pathway and the cell viability in H9c2 cardiomyocytes.Methods H9c2 cardiomyocytes were treated with or without non-selective or subtype selective M-receptor antagonists,then treated with carbachol or vehicle.The cell lysates were subjected to Western Blot to determine the phosphorylation level of MEK1/2 and ERK1/2.Alarma Blue assays were employed to measure the cell viability.Results M receptor stimulation with carbachol significantly increased the phosphorylation of MEK1/2 and ERK1/2,which was abrogated by atropine pretreatment,a non-selective M-receptor antagonist,and DAU 5584,an M3-receptor selective antagonist.M1-,M2-or M4-receptor selective antagonists did not block the effect of carbachol.In an cell survival/death model in H9c2 cardiomyocytes deprived of serum growth factors,carbachol increased the cell viability,an effect blocked by atropine and DAU 5584.Conclusion M3-receptor activates MEK1/2-ERK1/2 signaling pathway and promotes the cell survival response in H9c2 cardiomyocytes.
作者 张伟志 黄灿 杨一峰
机构地区 中南大学湘雅二医院小儿心脏外科
出处 《中南药学》 CAS 2011年第3期161-165,共5页 Central South Pharmacy
关键词 毒蕈碱型胆碱受体 MEK1/2-ERK1/2信号通路 H9C2心肌细胞 细胞生存 muscarinic acetylcholine receptor MEK1/2-ERK1/2 signaling pathway H9c2 cardiomyocyte cell survival
分类号 R963 [医药卫生—微生物与生化药学]
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参考文献20

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同被引文献35

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引证文献2

中南药学
2011年 第3期

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