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FEBS Lett. 1997 Jul 28;412(2):385-7.

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

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Institut für Anatomie und Zellbiologie II, Universität Heidelberg, Germany.


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 microg 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.

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