Role of cellular superoxide dismutase against reactive oxygen metabolite injury in cultured bovine aortic endothelial cells.
We examined the protective effect of cellular superoxide dismutase against extracellular hydrogen peroxide in cultured bovine aortic endothelial cells. 51Cr-labeled cells were exposed to hydrogen peroxide generated by glucose oxidase/glucose. Glucose oxidase caused a dose-dependent increase of 51Cr release. Pretreatment with diethyldithiocarbamate enhanced injury induced by glucose oxidase, corresponding with the degree of inhibition of endogenous superoxide dismutase activity. Inhibition of cellular superoxide dismutase by diethyldithiocarbamate was not associated either with alteration of other antioxidant defenses or with potentiation of nonoxidant injury. Enhanced glucose oxidase damage by diethyldithiocarbamate was prevented by chelating cellular iron. Inhibition of cellular xanthine oxidase neither prevented lysis by hydrogen peroxide nor diminished enhanced susceptibility by diethyldithiocarbamate. These results suggest that, in cultured endothelial cells: 1) cellular superoxide is involved in mediating hydrogen peroxide-induced damage; 2) superoxide, which would be generated upon exposure to excess hydrogen peroxide independently of cellular xanthine oxidase, promotes the Haber-Weiss reaction by initiating reduction of stored iron (Fe3+) to Fe2+; 3) cellular iron catalyzes the production of a more toxic species from these two oxygen metabolites; 4) cellular superoxide dismutase plays a critical role in preventing hydrogen peroxide damage by scavenging superoxide and consequently by inhibiting the generation of the toxic species.
Hiraishi
H
H
Department of Medicine, Veterans Affairs Medical Center, Long Beach, California 90822.
Terano
A
A
Razandi
M
M
Sugimoto
T
T
Harada
T
T
Ivey
K J
KJ
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000633:toxicity; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002860:Chromium Radioisotopes / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005949:Glucose Oxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007502:Iron Chelating Agents; D010100:Oxygen / Q000378:metabolism*; D010117:Oxypurinol / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D002860:Chromium Radioisotopes; D007502:Iron Chelating Agents; D000493:Allopurinol; D004050:Ditiocarb; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D013482:Superoxide Dismutase; D010117:Oxypurinol; D010100:Oxygen