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 (PPAR gamma) 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 clown-regulation of Bcl-2 protein. The PPAR gamma agonist rosiglitazone protected cardiomyocytes from oxidative stress and apoptosis. Cardiomyocytes constitutively overexpressing PPAR gamma were resistant to oxidative stress-induced apoptosis and protected against impairment of mitochondrial function. On the contrary, cells expressing a dominant negative mutant of PPAR gamma were highly sensitive to oxidative stress. Cells overexpressing PPAR gamma exhibited an almost 3 fold increase in Bcl-2 protein content: whereas, in PPAR gamma dominant negative expressing cells, Bcl-2 was barely detected. Bcl-2 knockdown by siRNA in cells overexpressing PPAR gamma results in increased sensitivity to oxidative stress, suggesting that Bcl-2 upregulation mediated the protective effects of PPAR gamma. These data suggest that, in oxidative stress-induced cardiomyocyte apoptosis, PPAR gamma protects cells from oxidative stress through upregulating Bcl-2 expression. These findings provide further support for the use of PPAR gamma agonists in ischemic cardiac disease. (C) 2009 Elsevier Inc. All rights reserved.