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 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.
Beier
K
K
Institut für Anatomie und Zellbiologie II, Universität Heidelberg, Germany. konstantin.beier@urz.uni-heidelberg.de
Völkl
A
A
Fahimi
H D
HD
D000199:Actins / Q000235:genetics; D042962:Acyl-CoA Oxidase; D000818:Animals; D002374:Catalase / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000199:Actins; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D010088:Oxidoreductases; D002374:Catalase; D042962:Acyl-CoA Oxidase