SCAD REGULATES CARDIOMYOCYTE APOPTOSIS THROUGH AMPK/PPARΑ/SCAD SIGNALLING PATHWAY

Jiawang Wang*, Zesheng Xu*, #, Qiong Wu**, Nan Guo*, Jing Yu*, Xufen Cao*

*Department of Cardiology, Tianjin Medical University Cangzhou Teaching Hospital, Cangzhou, PR China - **Department of Clinical Laboratory, Tianjin Medical University Cangzhou Teaching Hospital, Cangzhou, PR China

Objective: To analyse the effect of short-chain acyl coenzyme A dehydrogenase (SCAD) on cardiomyocyte apoptosis and its possible regulation mechanism.

Methods: T-butyl hydroperoxide (tBHP) was applied to cardiomyocytes, and a cardiomyocyte apoptosis model was established to detect changes in SCAD protein levels and cell viability in cardiomyocytes. Then siRNA-1186 was used to interfere with SCAD expression, and the change of SCAD protein level, cell survival rate and apoptotic rate after interference myocardial cells were detected. The change of SCAD and PPARα protein levels were determined by using PPARα agonist fenofibrate (Feno) for 30 min after treatment of cardiomyocytes. After pretreatment of cardiomyocytes with AMPK agonist AICAR for 30 min, tBHP was applied to cardiomyocytes to detect changes in SCAD, PPARα and phosphorylated adenylate-activated protein kinase alpha (p-AMPKα) protein expression levels.

Results: MMT colorimetry showed that the survival rate of cardiomyocytes decreased with increased concentrations of tBHP and longer times. The cell survival rate was 50% when the concentration of tBHP was 200 μmol/L at 6 hours. Western blotting showed that the expression of SCAD protein decreased significantly at 6 hours and the concentration of tBHP was 200 μmol/L (P<0.05). After siRNA-1186 was applied to cardiomyocytes, the expression of SCAD protein and the cell survival rate decreased significantly, while the apoptotic rate was significantly higher, which was consistent with the trend of apoptosis induced by tBHP. The expression levels of SCAD and PPARα protein in Feno+tBHP group were significantly higher than those in tBHP group (P<0.05). The expression level of SCAD, PPARα, and p-AMPKα protein in AICAR+tBHP group was significantly higher than that of tBHP group (P<0.05).

Conclusion: Up-regulation of SCAD expression may reduce the apoptosis rate of cardiomyocytes, and its mechanism may be related to the regulation of AMPK/PPARα/SCAD signalling pathway by SCAD. SCAD can be a new target to treat heart failure diseases.