The Effects And Mechanisms Of Perifosine Protecting Cardiomyocytes From Ischemic Reperfusion Injury

Aims:We found that perifosine, an Akt inhibitor, surprisingly protected cardiomyocytes from oxygen glucose deprivation (OGD)/re-oxygenation.The aim of the present study was to investigate the role of perifosine in protecting cardiomyocytes from ischemic reperfusion injury.Methods and Results:1. Detecting the effect of perifosine on different concentrations in H9c2 cardiomyocytes by MTT assay and flow cytometry assay.Detecting viability of cardiomyocytes underlow-concentration of perifosine-treated in different times.We found low-concentration of perifosine protected cardiomyocytes,and aslo protected them from oxygen glucose deprivation (OGD)/re-oxygenation.2. Detecting ROS production, mitochondrial CYP-D-p53 association and mitochondrial membrane potential (MMP) reduction in H9c2 cells.We found low-concentration of perifosine inhibited oxidative stresses caused by OGD/reoxygenation.3. Studying the role of AMPK activation in NADPH by low-concentration of perifosine,applying shRNA method to knockdown AMPKal in H9c2 cells and siRNA strategy to selectively and transiently knockdown AMPKa1.We found perifosine provoked cytoprotection against OGD/re-oxygenation was significantly attenuated.Conclusion:Our results demonstrate that perifosine offers cytoprotection in cardiomyocytes, and the cytoprotection is mainly through activating AMPK signalings. These findings suggest that low-concentration of perifosine plays a cardioprotective role in cardiomyocytes and it may have a therapeutic potential in ischemic heart disease.