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Am J Physiol Lung Cell Mol Physiol 283: L549-L554, 2002. First published April 19, 2002; doi:10.1152/ajplung.00018.2002
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Vol. 283, Issue 3, L549-L554, September 2002

Prenatal hypoxia decreases lung extracellular superoxide dismutase expression and activity

Brenda-Louise Giles1, Hagir Suliman2, Lisa B. Mamo3, Claude A. Piantadosi2, Tim D. Oury4, and Eva Nozik-Grayck3

1 Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba R3A 1S1; Departments of 2 Medicine and 3 Pediatrics, Duke University Medical Center, Durham, North Carolina 27710; and 4 Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Extracellular superoxide dismutase (EC-SOD), which scavenges extracellular superoxide (O<UP><SUB>2</SUB><SUP>−</SUP></UP>·), is highly regulated in the developing lung. In the prenatal rabbit, EC-SOD is predominantly intracellular and inactive, and postnatally, active EC-SOD is secreted. We hypothesized that prenatal hypoxia would delay the normal postnatal secretion of active EC-SOD in the lung. Pregnant New Zealand White rabbits were exposed to hypobaric hypoxia (15,000 ft × 36 h) to alter fetal O2 tension or were maintained in room air. Lungs were harvested from preterm (28 days), term (30 ± 1 day), and 1-wk-old kits. After prenatal hypobaric hypoxia, EC-SOD mRNA expression was significantly decreased in lungs of full-term kits, whereas EC-SOD protein decreased at all ages. Immunohistochemical staining for EC-SOD showed that hypoxia delayed secretion of the isoenzyme in the airways and pulmonary vasculature. Furthermore, pulmonary EC-SOD enzyme activity was significantly decreased in the 1-wk-old kits exposed to prenatal hypoxia. We conclude that prenatal hypoxia downregulates EC-SOD expression at both the transcriptional and posttranslational levels. Furthermore, prenatal hypoxia delays secretion of active EC-SOD enzyme. These findings have important implications for the effects of prenatal asphyxia on postnatal response to oxidant stress.

antioxidant; nitric oxide; lungs; neonatal; oxygen tension


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