Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury.
To determine the mechanism responsible for the enhanced susceptibility of endothelial cells to oxidant injury in the absence of glucose, we induced endothelial cell injury with oxygen radicals in the presence of various oxygen radical scavengers and measured endothelial cell levels of glutathione after oxidant injury in the presence and absence of glucose. Endothelial cells were damaged with toxic oxygen radicals generated by phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs) or xanthine-xanthine oxidase in the presence and absence of glucose and catalase (scavenger of hydrogen peroxide), superoxide dismutase (scavenger of superoxide radical), isoleucine, valine, and serine (scavengers of hypochlorous acid), or mannitol, ethanol, benzoic acid, dimethyl sulfoxide, and dimethyl thiourea (scavengers of hydroxyl radical). Endothelial cell injury was quantitated by 2-deoxy-[1-3H] glucose or chromium 51 release assays or both. In each oxidant-generating system, in the presence and absence of glucose, only catalase significantly protected endothelial cells from oxidant injury (P less than 0.001). When endothelial cells were damaged by hydrogen peroxide generated with xanthine-xanthine oxidase in the presence of glucose, endothelial cell levels of glutathione remained unchanged. In contrast, when endothelial cells were damaged with xanthine-xanthine oxidase in the absence of glucose, endothelial cell levels of glutathione fell to less than 50% of baseline (P less than 0.05). Xanthine-xanthine oxidase-mediated endothelial cell damage and depletion of glutathione in the absence of glucose were similar to results obtained in the presence of glucose when glutathione was depleted with buthionine sulfoximine, diethyl maleate, or 1-chloro-2,4-dinitrobenzene.(ABSTRACT TRUNCATED AT 250 WORDS)
D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008353:Mannitol / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000633:toxicity
D001565:Benzoates; D000431:Ethanol; D008353:Mannitol; C038983:1,3-dimethylthiourea; D019817:Benzoic Acid; D003847:Deoxyglucose; D006861:Hydrogen Peroxide; D002374:Catalase; D014969:Xanthine Oxidase; D005978:Glutathione; D013890:Thiourea; D005947:Glucose