Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1α
Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1α
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DOI：
10.1016/j.febslet.2005.02.065
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发表时间：
2005-04-11
期刊：
影响因子：
3.5
通讯作者：
Sato, T
中科院分区：
文献类型：
--
作者：
Kakinuma, Y;Ando, M;Sato, T
电刺激迷走神经可提高心肌梗死大鼠的存活率。然而，这种有益效果的机制尚不清楚。在常氧和低氧条件下，观察乙酰胆碱(ACh)对大鼠心肌细胞缺氧诱导因子-1α(HIF-1α)的影响。ACh翻译后调节HIF-1α，并使其在常氧下的蛋白水平升高。ACh增加Akt的磷酸化，Wortmannin或阿托品可阻断这一作用。ACh可阻止缺氧诱导的caspase-3激活和线粒体膜电位崩溃。显性负性HIF-1α抑制ACh的细胞保护作用。在急性心肌缺血时，迷走神经刺激可增加HIF-1α的表达，缩小心肌梗死面积。这些结果表明，ACh和迷走神经刺激通过PI3K/Akt/HIF-1α通路保护心肌细胞。(C)2005年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Electrical stimulation of the vagal efferent nerve improves the survival of myocardial infarcted rats. However, the mechanism for this beneficial effect is unclear. We investigated the effect of acetylcholine (ACh) on hypoxia-inducible factor (HIF)-1 alpha using rat cardiomyocytes under normoxia and hypoxia. ACh posttranslationally regulated HIF-1 alpha and increased its protein level under normoxia. ACh increased Akt phosphorylation, and wortmannin or atropine blocked this effect. Hypoxia-induced caspase-3 activation and mitochondrial membrane potential collapse were prevented by ACh. Dominant-negative HIF-1 alpha inhibited the cell protective effect of ACh. In acute myocardial ischemia, vagal nerve stimulation increased HIF-1 alpha expression and reduced the infarct size. These results suggest that ACh and vagal stimulation protect cardiomyocytes; through the PI3K/Akt/HIF-1 alpha pathway. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.