Arachidonic and docosahexaenoic acids differentially affect the expression of fatty acyl-CoA oxidase, protein kinase C and lipid peroxidation in HepG2 cells.
Arachidonic (AA) and docosahexaenoic (DHA) acids (5-20 microM), when supplemented to human hepatoma HepG2 cells, which are depleted in these long-chain polyunsaturated fatty acids in conventional culture conditions, enhance the expression of acyl-CoA oxidase (ACOX), the first enzyme in the peroxisomal beta-oxidation cycle. DHA is effective at lower concentrations (at 5 microM) and to a greater extent (about 60% increment) than AA (about 40%) at 20 microM. Protein kinase C (PKC) appears to be involved in the activity of AA on ACOX, but not in that of DHA, since only the effect of AA is prevented by the PKC inhibitor Staurosporine, and since a remarkable elevation of the PKC activator diacylglycerol occurs only after AA supplementation. AA also induces elevation of lipoperoxides, favoured by the relative vitamin E deficiency occurring in cultured cells, and this effect, which is prevented by supplementation of the vitamin, may contribute to PKC activation.
Risé
P
P
Institute of Pharmacological Sciences, University of Milan, Italy.
Galli
C
C
D042962:Acyl-CoA Oxidase; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008113:Liver Neoplasms; D051379:Mice; D010088:Oxidoreductases / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D004281:Docosahexaenoic Acids; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; D011493:Protein Kinase C