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Impairment of peroxisomal β-oxidation system by endotoxin treatment

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Abstract

It is now clear that peroxisomes play a crucial role in many cellular processes, including the β-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 β-oxidation enzyme system in rat liver. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment decreased the β-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 β-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 β-oxidation of very long chain fatty acids.

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Author notes

  1. Gursev Singh Dhaunsi

    Present address: University of Tennessee, 38115, Memphis, TN, USA

Authors and Affiliations

  1. Department of Pediatrics, Division of Developmental Neurogenetics, Medical University of South Carolina, 171 Ashley Avenue, 29425, Charleston, SC, USA

    Gursev Singh Dhaunsi, Coral Dawn Hanevold & Inderjit Singh

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  1. Gursev Singh Dhaunsi
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  2. Coral Dawn Hanevold
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  3. Inderjit Singh
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Dhaunsi, G.S., Hanevold, C.D. & Singh, I. Impairment of peroxisomal β-oxidation system by endotoxin treatment. Mol Cell Biochem 135, 187–193 (1994). https://doi.org/10.1007/BF00926522

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