McElroy, Mary Catherine (1990) The role of antioxidant enzymes in human lung development. University of Southampton, Doctoral Thesis.
Abstract
The expression of antioxidant enzymes in human fetal, neonatal and adult lungs was determined. Catalase activity increased by over 3 fold between 15 and 40 weeks gestation (20.9±7.8 to 73±27.5 μunits/mg protein) while glutathione peroxidase dismutase activities remained relatively constant. Since gestational age is only a guide to lung maturation status, the expression of antioxidant enzymes were compared with various indices of surfactant maturation. The well documented increase in lung disaturated phosphatidylcholine prior to term was shown to involve increases in the content and fractional contribution of PC16:0/16:0 and PC14:0/14:0. Lung catalase activity correlated with both PC16:0/16:0 (r= 0.79) and PC14:0/16:0 (r= 0.45) in lungs between 20 and 40 weeks post conceptual age. Immunoblots, comparing the expression of surfactant protein A, catalase, and superoxide dismutase demonstrated that the content of lung CAT increased as the lung matured while Cu7/Zn-SOD content was unchanged. To determine whether the pattern of antioxidant expression in lung was tissue specific, the development of these enzymes was also measured in human fetal and neonatal livers (11-52 weeks post conceptual age). In contrast with the lung, Cu/Zn-SOD activity increased during lung development while Mn-SOD, CAT and GSH-Px activities were relqatively constant. Antioxidant enzyme activities were determined in human fetal lungs maintained in organ culture. The activity changes in vitro with time in culture resemble those in vivo; catalase activity increased by 2 fold while SOD and GSH-Px both decreased. The antioxidant enzyme activities of explants were not affected by dexamethasone alone or in combination with tri-iodothyronine. The results suggest that the expression of catalase, superoxide dismutase and glutathione peroxidase activities are not coordinated during human lung or liver development. The increase in CAT in the lung and Cu/Zn-SOD in the liver may be due to increased tissue metabolic activity. The role of antioxidant enzymes is discussed in context of lung injury in pre-term infants.
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