TNF-alpha downregulates the peroxisome proliferator activated receptor-alpha and the mRNAs encoding peroxisomal proteins in rat liver

We have studied the effects of TNF-alpha on the mRNAs coding for the peroxisome proliferator activated receptor alpha (PPAR-alpha), and for catalase (Cat), acyl-CoA oxidase (AOX), multifunctional enzyme (PH), and beta-actin in rat liver, Total RNA was isolated from livers of male SD-rats 16 h after administration of a single dose of 25 mu g TNF-alpha and mRNAs were analyzed by a novel dot blot RNase protection assay, The mRNAs for PPAR-alpha and for Cat, AOX and PH were significantly reduced by TNF-treatment, In addition, the level of PPAR-alpha protein was also decreased after TNF, In contrast, the mRNA for beta-actin was markedly increased implying that the effect of TNF on PPAR-alpha and the peroxisomal mRNAs is highly selective, This effect may have important implications in perturbation of the lipid metabolism induced by TNF-alpha. (C) 1997 Federation of European Biochemical Societies.