Suppression of peroxisomal lipid beta-oxidation enzymes of TNF-alpha.
TNF-alpha is a potent cytokine which induces marked hyperlipidemia. Because of the important role of peroxisomes in lipid metabolism we investigated the effects of human recombinant TNF-alpha upon rat liver peroxisomal enzymes. Sixteen hours after the administration of a single dose of 25 micrograms of TNF-alpha to male rats the activity of peroxisomal fatty acyl-CoA oxidase was reduced by 50%. This was confirmed also by immunoblotting and by quantitative immunoelectron microscopy which in addition revealed substantial reduction of the trifunctional protein (hydratase-dehydrogenase-isomerase) in peroxisomes. These observations suggest that the suppression of peroxisomal beta-oxidation may contribute to the perturbation of the isomerase) in peroxisomes. These observations suggest that the suppression of peroxisomal beta-oxidation may contribute to the perturbation of the lipid metabolism induced by TNF-alpha.
Beier
K
K
Institut für Anatomie und Zellbiologie II, Universität Heidelberg, Germany.
Völkl
A
A
Fahimi
H D
HD
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000302:isolation & purification / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D004746:Enoyl-CoA Hydratase / Q000302:isolation & purification / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006949:Hyperlipidemias / Q000378:metabolism*; D007150:Immunohistochemistry; D007535:Isomerases; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000302:isolation & purification / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D063994:Peroxisomal Bifunctional Enzyme; D019998:Racemases and Epimerases / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D009097:Multienzyme Complexes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010088:Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042962:Acyl-CoA Oxidase; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases; D019998:Racemases and Epimerases