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, specifical ly the HO-1 isoenzyme, is regulated in oxidant stress and may also ser ve to Limit oxidative damage. However, it is not known whether neonata l lung HO-1 is regulated in hyper oxia specifically and, if so, what t ype of regulation occurs. Therefore, we attempted to answer these ques tions using newly born (<12 h) Wistar rats exposed to hyperoxia for 3 d. Neonatal rat lungs were evaluated daily for total HO activity, immu noreactive HO-1 protein, and steady state levels of HO-1 mRNA and comp ared with air-exposed controls. In neonatal rats, we noted an increase d lung HO activity after 3 d of hyperoxic exposure. Additionally, eval uation of HO activity after immunoprecipitation of HO-1 protein sugges ted that HO-1 contributed most of the increase in lung total HO activi ty observed in hyperoxia. Nonetheless, we did not see a significant di fference 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 st eady state levels of HO-1 mRNA on any day of hyperoxic exposure compar ed with air. We therefore conclude that neonatal rat lung HO-1 is regu lated in hyperoxia and speculate that the regulation of neonatal lung HO-1 occurs by posttranscriptional mechanisms, at least within the fir st days of hyperoxic exposure.