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Published ahead of print on April 29, 2004, doi:10.1164/rccm.200309-1282OC
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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 313-318, (2004)
© 2004 American Thoracic Society


Original Article

Discordant Extracellular Superoxide Dismutase Expression and Activity in Neonatal Hyperoxic Lung

Lisa B. Mamo, Hagir B. Suliman, Brenda-Louise Giles, Richard L. Auten, Claude A. Piantadosi and Eva Nozik-Grayck

Departments of Pediatrics and Medicine, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, University of Manitoba and Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada

Correspondence and reprint requests should be addressed to Eva Nozik-Grayck, M.D., 4200 E. Ninth Avenue B131, University of Colorado Health Sciences Center, Denver, CO 80262. E-mail: eva.grayck{at}uchsc.edu

Antioxidant defenses in the neonatal lung are required to adapt to the oxygen (O2)-rich postnatal environment, and oxidant/antioxidant imbalance is a predisposition to lung injury when high concentrations of inspired O2 are used in neonatal lung diseases. The lung's main extracellular enzymatic defense against superoxide, extracellular superoxide dismutase (EC-SOD), is closely regulated during development. In testing the hypothesis that developmental change in EC-SOD expression and activity in the immature lung would be disrupted by hyperoxia, we found a doubling of lung EC-SOD protein in newborn rats exposed to 95% O2 for 1 week. Furthermore, EC-SOD protein secretion increased, but EC-SOD enzyme activity did not change with O2 exposure. EC-SOD mRNA did not change at multiple points between 6 hours and 8 days. Lung EC-SOD recovered by immunoprecipitation after 1 week of O2 showed strong increases in protein nitrotyrosine and variable, nonsignificant differences in protein carbonyl content. These data provide the first direct evidence that EC-SOD is itself a target of nitration in hyperoxia, and offer a plausible explanation for low EC-SOD activity despite its increased secretion by O2-exposed neonatal lung.

Key Words: superoxide dismutase • antioxidant • oxygen • nitrotyrosine • protein carbonyl




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