The effect of bacterial endotoxin on synthesis of (Cu,Zn)superoxide dismutase in lungs of oxygen-exposed rats

Administration of bacterial endotoxin to rats exposed to greater than 95% O2 results in increased lung superoxide dismutase activity, decreased O2-induced lung damage, and a 3- to 4-fold improvement in survival rate (Frank, L., Yam, J., and Roberts, R. J. (1978) J. Clin. Invest, 61, 269-275). Antibodies to rat liver (Cu,Zn) superoxide dismutase were prepared and utilized to investigate the mechanism by which endotoxin treatment leads to increased lung superoxide dismutase activity. Assay of enzyme activity and of immunodetectable enzyme showed that the increased activity is due to an increase in the number of enzyme molecules rather than activation of existing enzyme. Compared to air controls, lung slices from rats exposed to greater than 95% O2 and treated with endotoxin have elevated rats of synthesis of (Cu,Zn)superoxide dismutase (51%) and of total protein (100%). Lung slices from untreated rats exposed to greater than 95% O2 have no such elevations. Endotoxin treatment thus appears to stimulate lung protein synthesis, leading to greater (Cu,Zn)superoxide dismutase activity due to an increased number of enzyme molecules.