Discordant extracellular superoxide dismutase expression and activity in neonatal hyperoxic lung.
Antioxidant defenses in the neonatal lung are required to adapt to the oxygen (O(2))-rich postnatal environment, and oxidant/antioxidant imbalance is a predisposition to lung injury when high concentrations of inspired O(2) 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% O(2) for 1 week. Furthermore, EC-SOD protein secretion increased, but EC-SOD enzyme activity did not change with O(2) 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 O(2) 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 O(2)-exposed neonatal lung.
Mamo
Lisa B
LB
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
Suliman
Hagir B
HB
Giles
Brenda-Louise
BL
Auten
Richard L
RL
Piantadosi
Claude A
CA
Nozik-Grayck
Eva
E
D000818:Animals; D000831:Animals, Newborn; D018496:Hyperoxia / Q000201:enzymology; D008168:Lung / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013482:Superoxide Dismutase / Q000378:metabolism*
C499089:Sod3 protein, rat; D013482:Superoxide Dismutase; D010100:Oxygen