title: Effect of glucagon and phorbol myristate acetate on oxidative demethylation and lipid peroxidation in isolated hepatocytes.
abstract: Oxidative demethylation of aminopyrine and peroxidation of endogenous lipids induced by cumene hydroperoxide were studied in hepatocytes isolated from fed male rats. Glucagon and phorbol-12-myristate-13-acetate (PMA) inhibited both processes in the concentration-dependent manner. Pretreatment of hepatocytes with 1 microM glucagon decreased oxidative demethylation by 75% and had a much smaller effect on lipid peroxidation. Preincubation with 1 microM PMA inhibited both processes by 25-30%. Phosphorylation of three isoforms of cytochrome P-450 was observed in microsomes isolated from hepatocytes incubated in the presence of [32P]orthophosphate. After incubation with PMA the phosphorylation of all these proteins was increased by 60-100%, whereas glucagon increased the phosphorylation of only one isoform. Consequences of the phosphorylation of various isoforms of cytochrome P-450 for metabolic functions of the monooxygenase system are discussed.
authors.affiliation: Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: A B
authors.initials: AB
authors.lastname: Wojtczak
authors.forename: K S
authors.initials: KS
authors.lastname: Famulski
authors.forename: M
authors.initials: M
authors.lastname: Buszkowska
authors.forename: P
authors.initials: P
authors.lastname: Latos
mesh_terms: D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D001555:Benzene Derivatives; D000632:Aminopyrine; D005934:Glucagon; D003577:Cytochrome P-450 Enzyme System; D013755:Tetradecanoylphorbol Acetate; C007164:cumene hydroperoxide