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Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non‐hypoxic induction of HIF‐1α
Author(s) -
Kakinuma Yoshihiko,
Ando Motonori,
Kuwabara Masanori,
Katare Rajesh G.,
Okudela Koji,
Kobayashi Masanobu,
Sato Takayuki
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.02.065
Subject(s) - acetylcholine , stimulation , hypoxia (environmental) , wortmannin , medicine , endocrinology , vagus nerve , chemistry , protein kinase b , phosphorylation , biochemistry , organic chemistry , oxygen
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)‐1α using rat cardiomyocytes under normoxia and hypoxia. ACh posttranslationally regulated HIF‐1α 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‐1α inhibited the cell protective effect of ACh. In acute myocardial ischemia, vagal nerve stimulation increased HIF‐1α expression and reduced the infarct size. These results suggest that ACh and vagal stimulation protect cardiomyocytes through the PI3K/Akt/HIF‐1α pathway.