Impairment of peroxisomal beta-oxidation system by endotoxin treatment.
It is now clear that peroxisomes play a crucial role in many cellular processes, including the beta-oxidation of very long chain fatty acids. Recently, mammalian peroxisomes have been shown to contain the antioxidant enzymes, superoxide dismutase and glutathione peroxidase, in addition to catalase. The presence of these enzymes in peroxisomes suggests that peroxisomes undergo oxidative stress in normal and disease states. As an indicator of the potential impact of an oxidative stress on peroxisomal functions, we evaluated the effect of endotoxin exposure on the beta-oxidation enzyme system in rat liver. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment decreased the beta-oxidation of lignoceric acid to 56% of control values (p < 0.01). The specific activity of the rate limiting enzyme in the system, acyl-CoA oxidase, was decreased to 73% of control values (p < 0.05). Immunoblot analysis revealed a 25% decrease in the 21KD subunit of the acyl-CoA oxidase protein. In contrast, the protein levels of the other enzymes in the pathway, trifunctional protein and 3-ketoacyl-CoA thiolase, were increased by 10 and 15%, respectively. These findings suggest that impairment of beta-oxidation of lignoceric acid by endotoxin treatment is due primarily to a reduction in the activity and protein level of the key enzyme, acyl-CoA oxidase. Oxidative stresses such as endotoxin exposure may have deleterious effects on important peroxisomal functions, such as beta-oxidation of very long chain fatty acids.
Dhaunsi
G S
GS
Department of Pediatrics, Medical University of South Carolina, Charleston 29425.
Hanevold
C D
CD
Singh
I
I
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007535:Isomerases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism; D063994:Peroxisomal Bifunctional Enzyme; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D005227:Fatty Acids; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042962:Acyl-CoA Oxidase; D000102:Acetyl-CoA C-Acyltransferase; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases; C010210:lignoceric acid