Red cells from glutathione peroxidase-1-deficient mice have nearly normal defenses against exogenous peroxides.
The role of glutathione peroxidase in red cell anti-oxidant defense was examined using erythrocytes from mice with a genetically engineered disruption of the glutathione peroxidase-1 (GSHPx-1) gene. Because GSHPx-1 is the sole glutathione peroxidase in the erythrocyte, all red cell GSH peroxidase activity was eliminated. Oxidation of hemoglobin and membrane lipids, using the cis-parinaric acid assay, was determined during oxidant challenge from cumene hydroperoxide and H(2)O(2). No difference was detected between wild-type red cells and GSHPx-1-deficient cells, even at high H(2)O(2) exposures. Thus, GSHPx-1 appears to play little or no role in the defense of the erythrocyte against exposure to peroxide. Simultaneous exposure to an H(2)O(2) flux and the catalase inhibitor 3-amino-1,2,4-triazole supported this conclusion. Hemoglobin oxidation occurred only when catalase was depleted. Circulating erythrocytes from the GSHPx-1-deficient mice exhibited a slight reduction in membrane thiols, indicating that high exposure to peroxides might occur naturally in the circulation. (Blood. 2000;96:1985-1988)
Johnson
R M
RM
Department of Biochemistry and Molecular Biology, Wayne State Medical School, Detroit, MI 48201, USA. rmjohns@med.wayne.edu
Goyette
G
G
Ravindranath
Y
Y
Ho
Y S
YS
D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D001555:Benzene Derivatives; D006454:Hemoglobins; D016877:Oxidants; D010545:Peroxides; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; C007164:cumene hydroperoxide