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Regulation of 1-cys Peroxiredoxin Expression in Lung Epithelial Cells

Institute for Environmental Medicine and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Address correspondence to: Aron B. Fisher, M.D., Institute for Environmental Medicine, University of Pennsylvania School of Medicine, 1 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6068. E-mail: abf{at}mail.med.upenn.edu

1-cys peroxiredoxin (1-cys Prx), the only member of a Prx subfamily that contains a single conserved cysteine residue, is abundant in lung. This bifunctional protein has both glutathione peroxidase and phospholipase A₂ activities compatible with a role both in protection against lung oxidant injury and also in lung phospholipid metabolism. Here we studied the developmental expression of 1-cys Prx in rat lungs and hormonal effects on protein expression in human and rat lung cells. There was little change in 1-cys Prx expression during the prenatal period, but a marked increase in expression immediately after birth. Enzymatic (peroxidase and phospholipase) activities increased gradually after birth and reached adult level at 7–14 postnatal days. Expression of the protein was induced in the presence of dexamethasone (Dex) in cultured human and rat lung epithelial cells and also was upregulated in neonatal rat lung in vivo. cAMP treatment had no effect on expression, although there was a modest synergistic effect when combined with Dex in human fetal lung epithelial cells. The increased expression of 1-cys Prx at birth may be important for surfactant phospholipid turnover related to the phopholipase A₂ activity of the protein and for antioxidant defense based on its peroxidase function.

Abbreviations: phospholipase A₂, aiPLA₂ • dexamethasone, Dex • fetal calf serum, FCS • gestational day, GD • glutathione peroxidase, GPx • glutathione, GSH • isobutylmethylxanthine, IBMX • minimal essential medium, MEM • phosphate-buffered saline, PBS • postnatal day, PD • peroxiredoxin, Prx • type II cells, TII cells

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