Increased glutathione in cultured hepatocytes associated with induction of cytochrome P-450. Lack of effect of glutathione depletion on induction of cytochrome P-450 and delta-aminolevulinate synthase.
Cellular glutathione concentrations in primary cultures of chick embryo hepatocytes were 15.3 +/- 5.3 nmoles/mg protein (mean +/- S.D.) and remained stable for up to 3 days in culture. The presence of insulin was not essential for the maintenance of glutathione concentrations. Induction of cytochrome P-450 by phenobarbital-like inducers (2-propyl-2-isopropylacetamide, 2-allyl-2-isopropylacetamide, and 2,4,5,2',4',5'-hexabromobiphenyl) was accompanied by 2- to 3-fold increases in glutathione concentrations and by increased glucuronidation of phenol red. The 3-methylcholanthrene-like inducers of cytochrome P-450 (beta-naphthoflavone and 3,4,3',4'-tetrachlorobiphenyl) did not have these effects. Glutathione was rapidly depleted to 15-30% of control levels in hepatocytes treated with buthionine sulfoximine, an inhibitor of gamma-glutamylcysteine synthase. No toxicity was observed with glutathione depletion. Glutathione depletion did not affect the ability of 2-propyl-2-isopropylacetamide to induce cytochrome P-450, glucuronidation of phenol red, or delta-aminolevulinate synthase.
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis*; D000502:Allylisopropylacetamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000032:analysis*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000032:analysis*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D008748:Methylcholanthrene / Q000494:pharmacology; D010637:Phenolsulfonphthalein / Q000378:metabolism
D005965:Glucuronates; D007328:Insulin; D008717:Methionine Sulfoximine; D000502:Allylisopropylacetamide; D019328:Buthionine Sulfoximine; D008748:Methylcholanthrene; C009072:propylisopropylacetamide; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase; D005978:Glutathione; D010637:Phenolsulfonphthalein