Prenatal hypoxia decreases lung extracellular superoxide dismutase expression and activity.
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.
Giles
Brenda-Louise
BL
Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba R3A 1S1.
Suliman
Hagir
H
Mamo
Lisa B
LB
Piantadosi
Claude A
CA
Oury
Tim D
TD
Nozik-Grayck
Eva
E
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*
D012333:RNA, Messenger; D013482:Superoxide Dismutase