title: Prenatal hypoxia decreases lung extracellular superoxide dismutase expression and activity.
abstract: Extracellular superoxide dismutase (EC-SOD), which scavenges extracellular superoxide (O.), 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 x 36 h) to alter fetal O(2) 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.
authors.affiliation: Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba R3A 1S1.
authors.forename: Brenda-Louise
authors.initials: BL
authors.lastname: Giles
authors.forename: Hagir
authors.initials: H
authors.lastname: Suliman
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Mamo
authors.forename: Claude A
authors.initials: CA
authors.lastname: Piantadosi
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
authors.forename: Eva
authors.initials: E
authors.lastname: Nozik-Grayck
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005110:Extracellular Space / Q000201:enzymology*; D005260:Female; D005865:Gestational Age; D000860:Hypoxia / Q000196:embryology*; D008168:Lung / Q000196:embryology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D013482:Superoxide Dismutase