Zivar Yousefipour
Texas Southern University, USA.
Title: Effects of PPARï¡-ligand-Clofibrate- on NO Production: Role of PKC and PKA
Biography
Biography: Zivar Yousefipour
Abstract
Nitric oxide (NO), an endogenous vasodilator, is a key regulator of basal vascular tone. Peroxisome proliferator activated receptor ï¡ (PPARï¡) ligand, clofibrate, has been reported to increase production of NO. Protein kinases C (PKC), a family of protein kinase enzymes, is involved in controlling the function of proteins through phosphorylation of hydroxyl groups of serine and threonine amino acid residues. Protein kinases A (PKA) is a cAMP-dependent protein kinase. There are evidence in support of clofibrate effect on NO production/availability independent of NO synthesis. Production of NO has been linked to protein kinases PKA and C-mediated signaling mechanisms. Therefore, we postulated that clofibrate-mediated increase in NO production might be attributed to PKA/PKC signaling pathway. We examined clofibrate mediated increase in NO production/availability in renal proximal tubular cells isolated from PPARï¡ knockout (KO) mice and the role of PKA/PKC signaling pathways using PKA 14-22 and chelerythrine, PKA and PKC inhibitors, respectively. Effect of clofibrate on eNOS and iNOS gene/protein expression was examined. Our result indicated reduced NO production in PPARï¡ KO mice compared to the WT. Addition of clofibrate enhanced NO production in both groups, which was abolished by L-NAME. Both PKC and PKA inhibitors reduced clofibrate-mediated NO production in both groups. Clofibrate increased eNOS and iNOS mRNA and iNOS protein expression in the KO but not in WT. Clofibrate did not affect PKA/PKC protein expression in either group. Our data suggest that clofibrate effect on NO production is through induction of iNOS gene and it is PPARï¡-independent mechanism.