Green tea extract selectively activates PPAR b/d in cultured cardiomyocytes

Hypoxia/reoxygenation (H/R) is one of the causes of the increased expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes. In a recent work we demonstrated that a single, high dose of green tea extract (GT) supplemented to the medium of cultured cardiomyocytes just before H/R is able to prevent the increased expression of iNOS, therefore reducing NO overproduction. In the present work we investigated on the mechanism by which GT reduces NO production. Since a molecular mechanism for polyphenol activity has been postulated, and peroxisome proliferator activated receptor (PPAR) activation is related to the transcription of iNOS gene, we evaluated the activation of PPARs by GT. Moderate GT concentration, supplemented to cardiomyocyte medium since the initial seeding, selectively activated PPAR /δ isoform. Furthermore, we observed a reduction in NO production and an increase in total antioxidant activity, indicating that GT components may act on both ROS, via an antioxidant mechanism, and NO overproduction. PPAR / activation could represent the key event in the reduction of NO production by GT. Although PPAR activation by GT was lower than activation by fenofibrate, it is very interesting to note that it was selective for the / isoform, at least in neonatal cardiomyocytes.