title: Induction of peroxiredoxin gene expression by oxygen in lungs of newborn primates.
abstract: Peroxiredoxin (Prx) is an important antioxidant defense enzyme that reduces hydrogen peroxide to molecular oxygen by using reducing equivalents from thioredoxin. We report that lung Prx I messenger RNA (mRNA) is specifically upregulated by oxygen. Throughout the third trimester, mRNA for Prx I was expressed 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 greater 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 develop chronic lung disease, lung Prx I mRNA also was increased on Days 1 and 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-needed oxygen. By contrast, there was a decrease in Prx activity in 140-d premature baboons exposed to 100% oxygen. In the lung explants from prematures (140 d), there was no significant increase in Prx activity in response to 24 h exposure to hyperoxia, whereas exposure of explants to 48 h hyperoxia caused 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 that protein kinase (PK) C activity increased when A549 cells were exposed to 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. The acute increase in gene expression of Prx I in response to oxygen suggests an important role for this protein during the transition from relatively anaerobic fetal life to oxygen-breathing at birth.
authors.affiliation: Department of Molecular Biology, University of Texas Health Center at Tyler, Tyler, Texas 75708, USA. kumuda.das@uthct.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Das
authors.forename: P M
authors.initials: PM
authors.lastname: Pahl
authors.forename: X L
authors.initials: XL
authors.lastname: Guo
authors.forename: C W
authors.initials: CW
authors.lastname: White
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D046508:Culture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D018496:Hyperoxia / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010215:Papio; D010544:Peroxidases / Q000235:genetics*; D054464:Peroxiredoxins; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D009281:Naphthalenes; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D003513:Cycloheximide; D010544:Peroxidases; D054464:Peroxiredoxins; D011493:Protein Kinase C; C058819:calphostin C; C070515:bisindolylmaleimide I; D010100:Oxygen