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Am J Physiol Lung Cell Mol Physiol 274: L313-L319, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 3, L313-L319, March 1998

Molecular mechanisms of antioxidant enzyme expression in lung during exposure to and recovery from hyperoxia

Linda Biadasz Clerch1,2, Donald Massaro1,3, and Alla Berkovich1,2

1 Lung Biology Laboratory, and Departments of 2 Pediatrics and 3 Medicine, Georgetown University School of Medicine, Washington, DC 20007-2197

Manganese superoxide dismutase (MnSOD) activity falls ~50% in lung during 48 h of exposure of adult rats to >95% O2 (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, making the phenomenon potentially more important to humans. In rats, a decrease in lung MnSOD activity during an initial 48 h of exposure to >95% O2 and its increase during an immediately subsequent 24 h in air were due to decreases and increases, respectively, in MnSOD specific activity and synthesis rate; the latter was due to altered translational efficiency. The concentration in the lung of copper-zinc superoxide dismutase mRNA, catalase mRNA, and glutathione peroxidase mRNA, unchanged during the initial 48 h of exposure to O2, rose approximately twofold during reexposure to O2 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 require therapy that maintains translational efficiency and MnSOD specific activity.

translational efficiency; manganese superoxide dismutase; catalase; copper-zinc superoxide dismutase; glutathione peroxidase; gene expression; baboons; rats


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