Induction of peroxiredoxin gene expression by oxygen in lungs of newborn primates

Peroxiredoxin (Prx) is an important antioxidant defense enzyme that reduces hydrogen peroxide to molecular oxygen by using reducing equivalents from t hioredoxin. We report that lung Prx I messenger RNA (mRNA) is specifically upregulated by oxygen. Throughout the third trimester, mRNA for Prx I was e xpressed constitutively at low levels in fetal baboon lung. However, after premature birth (125 or 140 d gestation), lung Prx I mRNA increased rapidly with the onset of oxygen exposure. Premature animals (140 d) breathing 100 % O-2 developed chronic lung disease within 7 to 14 d. These animals had gr eater lung Prx I mRNA after 1, 6, or 10 d of life than did fetal controls. In 140-d animals given lesser O-2 concentrations (as needed) that did not d evelop chronic lung disease, lung Prx I mRNA also was increased on Days I a nd 6, but not Day 10. In fetal distal lung explant culture, Prx I mRNA was elevated in 95% O-2, relative to 1% oxygen, and remained elevated at 24 h. Prx protein activity increased in 140-d premature baboons exposed to as-nee ded oxygen. By contrast, there was a decrease in Prx activity in 140-d prem ature baboons exposed to 100% oxygen. In the lung explants from prematures (140 d), there was no significant increase in Prx activity in response to 2 4 h exposure to hyperoxia, whereas exposure of explants to 48 h hyperoxia c aused a nonsignificant decrease in Prx activity. Treatment of lung explants with actinomycin D inhibited Prx mRNA increases in 95% oxygen, indicating transcriptional regulation. In cellular signaling studies we demonstrated t hat protein kinase (PK) C activity increased when A549 cells were exposed t o 95% oxygen, compared with 21% oxygen exposure. In lung explant cultures, specific PKC inhibitors calphostin C or GF109203X inhibited the increase in Prx I mRNA with 95% oxygen exposure, indicating PKC-mediated signaling. Th e acute increase in gene expression of Prx I in response to oxygen suggests an important role for this protein during the transition from relatively a naerobic fetal life to oxygen-breathing at birth.