Promotion of glutathione-gamma-glutamyl transpeptidase-dependent lipid peroxidation by copper and ceruloplasmin: the requirement for iron and the effects of antioxidants and antioxidant enzymes.
Oxidative damage (lipid peroxidation, LPO) induced in a completely defined system containing glutathione (GSH), purified gamma-glutamyl transpeptidase (GGT), and EDTA- and ADP-chelated ferric iron was enhanced by catalytic amounts of cupric ions and by ceruloplasmin (CP). The enhancement depended on GSH concentration, GGT activity, the presence of iron, and the chelation of copper by o-phenanthroline. High concentrations of CP inhibited LPO. Cu- and CP-enhanced, GSH-GGT-driven LPO was inhibited by the chain-breaking radical scavengers butylated hydroxyanisol, alpha-tocopherol, and Trolox C (a synthetic analog of alpha-tocopherol) but not by the hydroxyl scavenger mannitol. Ascorbic acid increased LPO in the presence of Cu or CP. Cu-enhanced LPO was partially sensitive to superoxide dismutase but not to catalase or horseradish peroxidase. The results indicate that Cu and CP enhance thiol-driven LPO and promote thiol-dependent mutagenesis by a very similar, if not the same, mechanism and are in agreement with the idea that this enhancement is due to redox reactions of chelated Cu and Fe, rather than to the reactivity of Cu in the Fenton reaction.
Glass
G A
GA
Department of Biochemistry, Tel-Aviv University, Ramat-Aviv, Israel.
Stark
A A
AA
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002570:Ceruloplasmin / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D006735:Horseradish Peroxidase / Q000378:metabolism / Q000494:pharmacology; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D016296:Mutagenesis / Q000187:drug effects; D009152:Mutagenicity Tests; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000378:metabolism*
D000975:Antioxidants; D016166:Free Radical Scavengers; D014810:Vitamin E; D003300:Copper; D007501:Iron; D006735:Horseradish Peroxidase; D002374:Catalase; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D005723:gamma-Glutamyltransferase; D005978:Glutathione