Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 Kinase/Akt

R. Aikawa, M. Nawano, Y. Gu, H. Katagiri, T. Asano, W. Zhu, R. Nagai, I. Komuro

研究成果: Article査読

194 被引用数 (Scopus)

抄録

Background - Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Reactive oxygen species induce apoptosis in many types of cells including cardiomyocytes. Because insulin has been reported to have protective effects, we examined whether insulin prevents cardiomyocytes from oxidative stress-induced apoptotic death. Methods and Results - Cultured cardiomyocytes of neonatal rats were stimulated by hydrogen peroxide (H2O2). Apoptosis was evaluated by means of the TUNEL method and DNA laddering. Incubation with 100 μmol/L H2O2 for 24 hours increased the number of TUNEL-positive cardiac myocytes (control, ≃4% versus H2O2, ≃23%). Pretreatment with 10-6 mol/L insulin significantly decreased the number of H2O2-induced TUNEL-positive cardiac myocytes (≃12%) and DNA fragmentation induced by H2O2. Pretreatment with a specific phosphatidylinositol 3 kinase (PI3K) inhibitor, wortmannin, and overexpression of dominant negative mutant of PI3K abolished the cytoprotective effect of insulin. Insulin strongly activated both PI3K and the putative downstream effector Akt. Moreover, a proapoptotic protein, Bad, was significantly phosphorylated and inactivated by insulin through PI3K. Conclusions - These results suggest that insulin protects cardiomyocytes from oxidative stress-induced apoptosis through the PI3K pathway.

本文言語English
ページ(範囲)2873-2879
ページ数7
ジャーナルCirculation
102
23
DOI
出版ステータスPublished - 2000 12月 5
外部発表はい

ASJC Scopus subject areas

  • 循環器および心血管医学
  • 生理学(医学)

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