Rat lung manganese superoxide dismutase (mnsod) expression: hyperoxia and translational regulation

Within 48 hours of exposure of adult rats to > 95% O₂ the concentration of MnSOD mRNA rises in the lung but MnSOD activity falls (J. Clin. Invest. 91. 499, 1993). We now show that a fall in hing MnSOD activity during exposure to > 95% O₂ is a more universal event; it also occurred in adult mice and adult baboons. In rats, the fall in MnSOD activity during exposure to > 95% O? was due to a decrease in its specific activity and in the concentration of MnSOD; the latter was due, at least in part, to a decrease in the rate of MnSOD synthesis. At the end of 24 hrs in air, following 48 hrs in > 95% Oj, hing MnSOD activity was higher than in rats never exposed to > 95% Oj. This increase was due to an increase in MnSOD specific activity and in the rate of MnSOD synthesis. The hing's translational efficiency (rate of MnSOD synthesis per molecule of MnSOD mRNA) was 2.1 in rats never exposed to > 95% Oj, 0.4 in rats after breathing > 95% Ch for 48 hrs, and 1.1 after 24 hrs in air following 48 hrs in > 95% O₂. We conclude, the fill in MnSOD activity during exposure to > 95% O₂ is due to unpaired translation and to inactivation or a failure of activation of the enzyme; these defects were reversed following removal of rats from > 95% Oz.