Down-regulation of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase by polyunsaturated fatty acids in hepatocytes is not mediated by PPARα

Abstract

Dietary polyunsaturated fatty acid (PUFA) suppresses hepatic α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) [EC4.1.1.45] activity and mRNA level in rats. In this study, to examine whether down-regulation of ACMSD mRNA by PUFA involves PPARα-mediated mechanism or not, we investigated the effect of PUFA on the ACMSD level by using primary cultured rat hepatocytes. The primary cultured hepatocytes which were isolated from rats were incubated with fatty acids, WY-14,643 (a PPARα agonist) and/or MK-886 (a PPARα antagonist). ACMSD and acyl-CoA oxidase (ACO) as peroxisome marker enzyme mRNA level levels were determined by competitive RT-PCR method. These results lead us to the conclusion that the mechanism of decreased level of ACMSD mRNA by PUFA was different from that by WY-14,643, suggesting that there would be pathways other than a PPARα-mediated one for PUFA to regulate ACMSD mRNA level.