Am. J. Respir. Cell Mol. Biol.,
Volume 25, Number 2, August, 2001 226-232
Induction of Peroxiredoxin Gene Expression by Oxygen in
Lungs of Newborn Primates
Kumuda C.
Das,
Paula M. B.
Pahl,
Xiao-Ling
Guo,
and
Carl W.
White
Department of Molecular Biology, University of Texas Health Center at Tyler, Tyler, Texas; Department of Medicine, University of
Colorado Health Sciences Center; Department of Pediatrics, National Jewish Medical and Research Center; and University of Colorado
Health Sciences Center, Denver, Colorado
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% O2
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 O2 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% O2, 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.
Abbreviations: bronchopulmonary dysplasia, BPD; complementary DNA,
cDNA; guanidinium isothiocyanate, GITC; hydrogen peroxide, H2O2;
messenger RNA, mRNA; nicotinamide adenine dinucleotide phosphate, NADPH; protein kinase, PK; pro re nada (as-needed), prn; peroxiredoxin, Prx; ribosomal RNA, rRNA; thioredoxin, Trx.
