Hyperoxic regulation of lung heme oxygenase in neonatal rats.
In the neonatal lung, hyperoxic exposure is associated with induction of various genes and critical antioxidants. Heme oxygenase, specifically the HO-1 isoenzyme, is regulated in oxidant stress and may also serve to limit oxidative damage. However, it is not known whether neonatal lung HO-1 is regulated in hyperoxia specifically and, if so, what type of regulation occurs. Therefore, we attempted to answer these questions using newly born (< 12 h) Wistar rats exposed to hyperoxia for 3 d. Neonatal rat lungs were evaluated daily for total HO activity, immunoreactive HO-1 protein, and steady state levels of HO-1 mRNA and compared with air-exposed controls. In neonatal rats, we noted an increased lung HO activity after 3 d of hyperoxic exposure. Additionally, evaluation of HO activity after immunoprecipitation of HO-1 protein suggested that HO-1 contributed most of the increase in lung total HO activity observed in hyperoxia. Nonetheless, we did not see a significant difference in immunoreactive HO-1 protein in neonatal lungs after 3 d of hyperoxic exposure, although we did so on d 2. Also, in contrast with previous reports, we did not detect any significant differences in steady state levels of HO-1 mRNA on any day of hyperoxic exposure compared with air. We therefore conclude that neonatal rat lung HO-1 is regulated in hyperoxia and speculate that the regulation of neonatal lung HO-1 occurs by posttranscriptional mechanisms, at least within the first days of hyperoxic exposure.
Dennery
P A
PA
Stanford University School of Medicine, California 94305, USA.
Rodgers
P A
PA
Lum
M A
MA
Jennings
B C
BC
Shokoohi
V
V
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D018496:Hyperoxia; D007527:Isoenzymes / Q000096:biosynthesis; D015227:Lipid Peroxidation; D008168:Lung / Q000201:enzymology* / Q000254:growth & development; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D006419:Heme Oxygenase (Decyclizing)