Protection by glutathione and other thiol compounds against the loss of protein thiols and tocopherol homologs during microsomal lipid peroxidation.
Microsomes from rat liver were used to investigate the mechanisms by which thiol compounds protect cellular membranes against damage from oxidants. Glutathione (GSH), dihydrolipoate and dithioerythritol, but not cysteine, ameliorated the loss of thiol groups of microsomal proteins attacked by Fe/ADP/NADPH or Fe/ADP/ascorbate prooxidant systems. The protection by GSH, but not dihydrolipoate or dithioerythritol, appeared to be enzymic since it was lost after microsomes were heated or treated with trypsin. The blocking of microsomal protein thiols with N-ethylmaleimide also diminished the protective effect of GSH. Lipid peroxidation, as assessed by chemiluminescence and vitamin-E loss, was inhibited in parallel with the protection of protein thiols. In microsomes lacking vitamin E, the protection of protein thiols by exogenous thiols was diminished. However, the GSH-dependent protection of vitamin E showed no preference for alpha-tocopherol over other tocopherol homologs. It is suggested that a GSH-dependent enzyme maintains protein thiols in the face of oxidative damage during microsomal peroxidation. A maintenance of protein thiols might not only protect important metabolic functions, but may also afford an antioxidant capacity to membranes, and account for one facet of the GSH-dependent inhibition of lipid peroxidation.
Murphy
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ME
Institut für Physiologische Chemie I, Heinrich-Heine Universität Düsseldorf, Federal Republic of Germany.
Scholich
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H
Sies
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D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004226:Dithioerythritol / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008163:Luminescent Measurements; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014810:Vitamin E / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D014810:Vitamin E; D009249:NADP; D000244:Adenosine Diphosphate; D004226:Dithioerythritol; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D007501:Iron; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid