Differential Gene Expression of Antioxidant Enzymes in the Perinatal Rat Lung

Abstract

ABSTRACT. It has been previously demonstrated that the developing rat lung markedly increases its catalase (CAT) and glutathione peroxidase (GP) activities during the final 10 to 15% of gestation. In the present studies, we tested whether four major antioxidant enzymes (AOE) in perinatal rat lungs might share a similar pattern of developmental AOE gene expression via a pretranslational mechanism. The left lungs of 18-d to term fetuses and early postnatal rat pups were used to measure the concentrations of AOE mRNA by solution hybridization and the right lungs of the same group of animals were assayed for AOE activities. Results revealed differential AOE gene expression in developing rat lungs. Whereas the CAT and G P activities progressively increased prenatally, the superoxide dismutase (SOD) activity either declined [copper-zinc SOD (Cu,ZnSOD)] or remained constant [manganese SOD (MnSOD)] in late gestation. Postnatally, Cu,ZnSOD and CAT activities progressively increased, whereas MnSOD remained constant and G P activity declined slightly. For Cu,ZnSOD, MnSOD, and CAT, the activity changes were generally consistent with the patterns of changes in their mRNA concentrations in both the prenatal and postnatal period, but for G P they were not. At the time of birth, however, the mRNA levels of Cu,ZnSOD and CAT decreased -40%, whereas their enzyme activities increased. For MnSOD, only a slight rise in mRNA level was observed versus -100% increase in its activity at the time of birth. These findings suggest that the AOE are not coordinately regulated, and that developmental regulation of AOE gene expression in the perinatal rat lung is complex and likely exerted at different levels of regulation. (Pediatr Res 34: 27-31,1993)

Immunohistochemical Localization and Quantitative Analysis of Superoxide Dismutases in Fetal and Neonatal Rat Tissues: Fluorescence Microscopy Image Analysis.

“…In contrast to our data on immunoreactive SOD [11,12], recent studies showed a wide range of discrepancy between the activity and the m-RNA levels of antioxidant enzymes in fetal rodent organs [4,6]. According to these studies, the expression of antioxidant enzymes appeared to be regulated in a highly variable manner at both the transcriptional and posttranscriptional levels .…”

“…Chen et al [4] observed slight perinatal increases in the activities of rat lung CuZnSOD and GSHPx, whereas the m-RNA levels, in contrast, markedly decreased during the same period. Discrepancies between the changes in the levels of m-RNA and proteins were also found in the series of De Haan et al [6].…”

Neonatal Hyperoxia Increases Sensitivity of Adult Mice to Bleomycin-Induced Lung Fibrosis

“…Such changes have been attributed to early-life exposure to oxygen and cytotoxic reactive oxygen species that injure or reprogram the development of the lungs, eyes, and brain. The lungs of preterm infants are especially at risk for oxidative damage, because antioxidant defenses do not mature until late in gestation (10,11). Consistent with this concept, oxygen supplementation in the neonatal period has been directly associated with altered lung function later in life (12,13).…”

Neonatal Hyperoxia Increases Sensitivity Of Adult Mice To Bleomycin-Induced Lung Fibrosis

“…Such changes have been attributed to early-life exposure to oxygen and cytotoxic reactive oxygen species that injure or reprogram the development of the lungs, eyes, and brain. The lungs of preterm infants are especially at risk for oxidative damage, because antioxidant defenses do not mature until late in gestation (10,11). Consistent with this concept, oxygen supplementation in the neonatal period has been directly associated with altered lung function later in life (12,13).…”