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Hyperoxia Induces Thioredoxin and Thioredoxin Reductase Gene Expression in Lungs of Premature Baboons With Respiratory Distress and Bronchopulmonary Dysplasia^*

^* From the National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Carl W. White, MD, University of Colorado Health Sciences Center, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80106

Thioredoxin (TRX) is a potent protein disulfide reductase involved in antioxidant defense, signal transduction, and cellular proliferation. Messenger RNAs (mRNAs) for TRX and its reductase, TR, are specifically upregulated at birth by oxygen. After premature birth (125 or 140 of 185 days), both mRNAs increased rapidly in response to oxygen. In 140-day animals, who develop bronchopulmonary dysplasia (BPD) only after breathing 100% oxygen for 10 days, TRX and TR mRNAs were increased at 1, 6, and 10 days relative to 140-day fetal lung. By contrast, 140-day animals ventilated only with as needed oxygen do not develop BPD and express elevated TRX and TR messages only at days 1 and 6 of life. Newborn baboons of 125 days' gestation develop BPD even with as needed oxygen ventilation, and also develop sustained TRX and TR mRNA elevation. The acute response and the role of oxygen were examined further in fetal distal lung explant culture. There, as in vivo, mRNAs for TRX and TR were elevated within 24 h of exposure to 95% oxygen relative to those grown in 1% oxygen to simulate fetal oxygen tension. By contrast, TRX protein did not increase in lung explants from prematures (125 or 140 days), but did in those from near term (175 days) fetal baboons, after exposure to hyperoxia. Although TRX protein and activity, as well as TR activity, eventually did increase in all gestational-age newborns in response to hyperoxia (6 days), the in vitro data indicate that the TRX protein response was delayed in prematures. Increases in TRX or TR mRNA in response to 95% oxygen also were observed in adult baboon lung in explant culture and, to a lesser extent, in human lung epithelial-like A549 cells. When TRX oxidation-reduction (redox) status was determined, increased oxygen tension shifted TRX to its oxidized form. The acute increase in gene expression for both TRX and TR in response to oxygen suggests an important role for these proteins during the transition from relatively anaerobic fetal life to oxygen breathing at birth, and the even greater induction during hyperoxic exposure in respiratory distress suggests both a defensive role and a potential role in the pathophysiology of respiratory distress and BPD.

This Article Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Das, K. C. Articles by White, C. W. Search for Related Content PubMed PubMed Citation Articles by Das, K. C. Articles by White, C. W.