The alteration of superoxide dismutase, catalase, glutathione peroxidase, and NAD(P)H cytochrome c reductase in guinea pig polymorphonuclear leukocytes and alveolar macrophages during hyperoxia.
Superoxide dismutase, catalase, glutathione peroxidase and NAD(P)H cytochrome c reductase were quantitated in polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM) obtained from guinea pigs exposed up to 90 h to 85% oxygen. PMN and AM were sonicated and separated into a 16,000-g pellet, a 100,000-g pellet, and a 100,00-g supernate. Superoxide dismutase activity increased in both cells within 18 h, persisted for 66 h and decreased by 90 h. The highest rate of increase was in the 100,000-g pellet containing 3.4% of total enzyme activity in PMN but 28% in AM. The enzyme induction in PMN and AM was partially inhibited by daily intracardiac injections of 50 mg/kg actinomycin D. During oxygen exposure, catalase activity in PMN and AM decreased to 60% of its original activity, and gluthathione peroxidase was reduced in PMN to 60% and in AM to 20% of control values. Although NAD(P)H cytochrome c reductase decreased to 50% in PMN, no change was noted in AM. Upon exposure to superoxide anion, purified catalase, the glutathione peroxidase of the 100,000-g supernate, NADH, and NADPH cytochrome c reductases of the 16,000-g pellet decreased to 66+/-5%, 72+/-4%, 52+/-8%, and 40+/-9%, respectively, of their original activity. This inactivation was prevented by 0.1 mg superoxide dismutase. These in vitro observations could explain the decreased catalase and glutathione peroxidase activity demonstrated in vivo that may lead to an intracellular accumulation of hydrogen peroxide. Increased hydrogen peroxide concentrations have been found to inactivate superoxide dismutase thus impairing the first defense mechanism against superoxide anion.
D000818:Animals; D002374:Catalase / Q000378:metabolism*; D003579:Cytochrome Reductases / Q000378:metabolism*; D003609:Dactinomycin; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006168:Guinea Pigs; D008264:Macrophages / Q000201:enzymology*; D008954:Models, Biological; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D010100:Oxygen; D010544:Peroxidases / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
D003609:Dactinomycin; D010544:Peroxidases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003579:Cytochrome Reductases; D009251:NADPH-Ferrihemoprotein Reductase; D010100:Oxygen