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. Isolated adult rat hearts were subjected to 30 min regional ischemia followed by reperfusion with or without insulin (10(-7)mol/L) at the onset of reperfusion. Reperfusion with insulin inhibited myocardial apoptosis and reduced infarct size, along with significantly up-regulated myocardial SVV expression (5.9±0.3 Group MI/R+Ins vs. 2.1±0.1 Group MI/R, p<0.05) and increased phosphorylations of mTOR and p70S6K compared with I/R group, which was blocked by pretreatment of PI3K inhibitor LY294002. Rapamycin, a specific mTOR inhibitor, did not alter insulin-induced Akt phosphorylation but significantly inhibited SVV expression (from 6.1±0.3 to 3.0±0.15, p<0.05). Moreover, rapamycin blunted insulin-induced anti-apoptosis in the I/R hearts (8.1±0.4% vs. 16.5±1.8%, p<0.05). 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.

Si R ，Tao L ，Zhang HF ，Yu QJ ，Zhang R ，Lv AL ，Zhou N ，Cao F ，Guo WY ，Ren J ，Wang HC ，Gao F ... -  《-》

NDRG2: a newly identified mediator of insulin cardioprotection against myocardial ischemia-reperfusion injury.

Sun Z ，Tong G ，Ma N ，Li J ，Li X ，Li S ，Zhou J ，Xiong L ，Cao F ，Yao L ，Wang H ，Shen L ... -  《-》

Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism.

Zhang KR ，Liu HT ，Zhang HF ，Zhang QJ ，Li QX ，Yu QJ ，Guo WY ，Wang HC ，Gao F ... -  《APOPTOSIS》

Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes.

Chen S ，Liu J ，Liu X ，Fu Y ，Zhang M ，Lin Q ，Zhu J ，Mai L ，Shan Z ，Yu X ，Yang M ，Lin S ... -  《-》

Insulin protects isolated hearts from ischemia/reperfusion injury: cross-talk between PI3-K/Akt and JNKs.

Liu HT ，Zhang HF ，Si R ，Zhang QJ ，Zhang KR ，Guo WY ，Wang HC ，Gao F ... -  《-》