Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1α

Yoshihiko Kakinuma, Motonori Ando, Masanori Kuwabara, Rajesh G. Katare, Koji Okudela, Masanobu Kobayashi, Takayuki Sato

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2111-2118
Number of pages8
JournalFEBS Letters
Volume579
Issue number10
DOIs
Publication statusPublished - Apr 11 2005

Keywords

  • Acetylcholine
  • Apoptosis
  • Ischemia
  • Protein kinases

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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