Glutathione peroxidase compensates for the hypersensitivity of Cu,Zn-superoxide dismutase overproducers to oxidant stress.
The balance between several components of the antioxidant defenses appears to be important for the cellular resistance to oxidative stress. While Cu,Zn-superoxide dismutase (SOD) transfectants of mouse epidermal cells JB6 clone 41 were sensitized to oxidants produced by xanthine/xanthine oxidase (X/XO) consecutive transfection with catalase corrected their hypersensitivity (Amstad, P., Peskin, A., Shah, G., Mirault, M. E., Moret, R., Zbinden, I., and Cerutti, P. (1991) Biochemistry 30, 9305-9313). We studied the effect of the transfection of bovine selenoglutathione peroxidase (GPx) on the sensitivity of JB6 clone 41 and its SOD transfectants. Sensitivity to DNA strand breakage and killing by X/XO was reversely related to the activity ratios GPx over SOD. A GPx-transfectant of JB6 clone 41 cells with a GPx/SOD ratio of 3.8 was very strongly protected. The hypersensitivity of the SOD clones with GPx/SOD ratios of 0.4 was corrected or overcorrected by secondary transfection with bovine Se-GPx resulting in increased activity ratios GPx/SOD of 1 to 2.4. Our results indicate that small deviations from the physiological activity ratios of GPx/SOD have a dramatic effect on the resistance of cells to oxidant-induced damage to the genome and cell killing.
Amstad
P
P
Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Lausanne.
Moret
R
R
Cerutti
P
P
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002999:Clone Cells; D004249:DNA Damage; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D016877:Oxidants / Q000633:toxicity*; D012867:Skin; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection; D019820:Xanthine; D014969:Xanthine Oxidase / Q000633:toxicity*; D014970:Xanthines / Q000633:toxicity*
D007527:Isoenzymes; D016877:Oxidants; D014970:Xanthines; D019820:Xanthine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase