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Am J Physiol Lung Cell Mol Physiol 257: L61-L64, 1989;
1040-0605/89 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 257, Issue 2 61-L64, Copyright © 1989 by American Physiological Society

ARTICLES

Endotoxin increases lung Cu,Zn superoxide dismutase mRNA: O2 raises enzyme synthesis

J. Iqbal, L. B. Clerch, M. A. Hass, L. Frank and D. Massaro
Calvin and Flavia Oak Asthma Research and Treatment Facility, University of Miami School of Medicine, Florida 33136.

Administration of endotoxin to adult rats increases lung Cu,Zn superoxide activity after 72 h of exposure to greater than 95% O2. The increased activity is brought about mainly by a faster rate of Cu,Zn superoxide dismutase synthesis; rats treated with endotoxin but not exposed to hyperoxia do not exhibit these findings (Hass, Frank, and Massaro, J. Biol. Chem. 257: 9379-9383, 1982). We now report that 48 h after treatment of adult rats with endotoxin there was a decreased rate of Cu,Zn superoxide dismutase synthesis by lung slices from air- and O2- exposed rats, although, in both groups, the lung concentration of Cu,Zn superoxide dismutase mRNA was increased approximately 45%. Exposure of endotoxin-treated rats to greater than 95% O2 or air for an additional 24 h (72 h all told) resulted in continued elevation of Cu,Zn superoxide dismutase mRNA only in lungs of O2- exposed rats. In vitro exposure of lung slices from air-breathing saline- or endotoxin-treated rats to 95% O2 for 6 h led to an increased rate of Cu,Zn superoxide dismutase synthesis only in slices from endotoxin-treated rats. We conclude that endotoxin treatment leads to an increased concentration of Cu,Zn superoxide dismutase mRNA in rat lungs, but a sustained elevation of the mRNA, and its translation into an increased rate of Cu,Zn superoxide dismutase synthesis requires exposure of the lung to hyperoxia.


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