PPAR gamma protects cardiomyocytes against oxidative stress and apoptosis via Bcl-2 upregulation

Cardiovascular disease (CVD) is a leading cause of death and disabilities worldwide. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists possess potent anti-inflammatory actions and have recently emerged as potential therapeutic agents for CVD. Here we show that H₂O₂ induced apoptosis in cardiomyocytes with a marked down-regulation of Bcl-2 protein. The PPARγ agonist rosiglitazone protected cardiomyocytes from oxidative stress and apoptosis. Cardiomyocytes constitutively overexpressing PPARγ were resistant to oxidative stress-induced apoptosis and protected against impairment of mitochondrial function. On the contrary, cells expressing a dominant negative mutant of PPARγ were highly sensitive to oxidative stress. Cells overexpressing PPARγ exhibited an almost 3 fold increase in Bcl-2 protein content; whereas, in PPARγ dominant negative expressing cells, Bcl-2 was barely detected. Bcl-2 knockdown by siRNA in cells overexpressing PPARγ results in increased sensitivity to oxidative stress, suggesting that Bcl-2 up-regulation mediated the protective effects of PPARγ. These data suggest that, in oxidative stress-induced cardiomyocyte apoptosis, PPARγ protects cells from oxidative stress through upregulating Bcl-2 expression. These findings provide further support for the use of PPARγ agonists in ischemic cardiac disease.