Regulation of Paraoxonase1 Expression and Activity By PPARα in Liver Cell Lines

Abstract

Objective: The aim of this study is to investigate the effect of peroxisome proliferator activated receptor-alpha (PPAR alpha) ligands on the expression and activity of paraoxonase1 (PON1) enzyme and on the PPAR alpha receptor protein expression in human hepatocellular carcinoma and rat hepatoma cell lines. Materials and Methods: Cultured human hepatocellular carcinoma (HepG2) and rat hepatoma (MH-7777A) cells were incubated with PPAR alpha ligands (WY-14,643 and fenofibrate). PON1 activity was measured spectrophotometrically through paraoxon and phenylacetate hydrolysis. PON1 and PPAR alpha expressions have been evaluated by western blotting. Results: Both PPARa ligands increased PON1 expression in MH-7777 Acells. In HepG2 cells only fenofibrate slightly increased PON1 expression. In both cell lines, PPAR alpha ligands increased PPAR alpha expression, with WY-14,643 having a more prominent effect. It has been observed that the increase in PON1 expression did not correlate with the enzyme activity. Conclusion: This study shows that PPAR alpha ligands regulate in vitro the expression of PON1 enzyme, that has a protective role against atherosclerosis, in a ligand and species dependent manner. A better understanding of interactions between molecules involved in atherosclerosis will provide crucial information in the therapy and prevention of cardiovascular diseases.