PUMA MEDIATES THE APOPTOTIC SIGNAL OF HYPOXIA/REOXYGENATION IN CARDIOMYOCYTES THROUGH MITOCHONDRIAL PATHWAY

P53 upregulated modulator of apoptosis (PUMA) plays an important role in mediating cell death. However, the role of PUMA in cardiomyocyte death induced by hypoxia/reoxygenation (H/R) and its molecular mechanism still remain enigmatic. Here, we used the in vitro model to elucidate the effects of PUMA on H/R-induced cardiomyocyte apoptosis as well as the underlying mechanisms. We reported that H/R could upregulate the expression of PUMA accompanied by the elevation of cardiomyocyte apoptosis. Interestingly, inhibition of endogenous PUMA expression by PUMA siRNA or p53 inhibitor repressed H/R-induced cardiomyocyte apoptosis. Furthermore, we found H/R stimulated the associations of PUMA apoptosis repressor with caspase recruitment domain (ARC) and consequently attenuated the associations of ARC with caspase 8, resulting in caspase 8 activation. Also, H/R stimulated cytochrome C release and caspase 3 activation. However, these stimulating effects of H/R disappeared upon knockdown of endogenous PUMA. Our data reveal that PUMA participates in H/R-triggered cardiomyocyte apoptosis by interfering with mitochondrial pathway.