MOLECULAR MECHANISMS OF ANTIOXIDANT ENZYME EXPRESSION IN LUNG DURING EXPOSURE TO AND RECOVERY FROM HYPEROXIA

Manganese superoxide dismutase (MnSOD) activity falls similar to 50% i n lung during 48 h of exposure of adult rats to >95% O-2 (L. B. Clerch and D. Massaro. J. CLin. Invest. 91: 499-508, 1993). We now show that hyperoxia also decreased MnSOD activity in lungs of adult baboons, ma king the phenomenon potentially more important to humans. In rats, a d ecrease in lung MnSOD activity during an initial 48 h of exposure to > 95% O-2 and its increase during an immediately subsequent 24 h in air were due to decreases and increases, respectively, in MnSOD specific a ctivity and synthesis rate; the latter was due to altered translationa l efficiency. The concentration in the lung of copper-zinc superoxide dismutase mRNA, catalase mRNA, and glutathione peroxidase mRNA, unchan ged during the initial 48 h of exposure to O-2, rose approximately two fold during reexposure to Oz after 24 h in air. The demonstration that the fall in MnSOD activity is translationally and posttranslationally regulated during the initial exposure to hyperoxia suggests that gene transfer to increase MnSOD activity in hyperoxic lungs may also requi re therapy that maintains translational efficiency and MnSOD specific activity.