Journal of molecular and cellular cardiology
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J. Mol. Cell. Cardiol. · Jan 2011
Survivin: a novel player in insulin cardioprotection against myocardial ischemia/reperfusion injury.
Insulin inhibits ischemia/reperfusion-induced myocardial apoptosis through the activation of a survival signaling cascade including the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. However, the down-stream mechanism of PI3K remains elusive. This study is aimed at investigating whether survivin (SVV) plays a role in the insulin-induced anti-apoptotic effect in the ischemic/reperfused (I/R) hearts, and if so, further determining the signaling mechanism involved. ⋯ To further ascertain the role of SVV in insulin-induced cardioprotection, cardiomyocytes were transfected with adenovirus encoding SVV (gain-of-function) or siRNA targeting SVV (loss-of-function). Overexpression of SVV decreased I/R-induced cardiomyocyte apoptosis in vitro, while siRNA targeting SVV significantly blunted the anti-apoptotic effect of insulin. Taken together, these results suggest a novel role of PI3K/Akt/mTOR/SVV signaling in the cardioprotective effect of insulin.