Heme oxygenase-1 (HO-1), the rate-limiting enzyme of heme degradation and antioxidant defense protein, is induced in the lungs of animals exposed to hyperoxia. However, high levels of HO-1 expression may be deleterious, thus necessitating tight regulation. Previous reports show maturational differences in rat HO-1 regulation in hyperoxia, as newborns do not up-regulate HO-1mRNA compared with adults. To better understand the differential response of lung HO-1 to hyperoxia, we exposed newborn and adult mice to >95% oxygen. The newborn lungs had reduced HO-1 mRNA induction compared with adults and newborn transgenic mice over-expressing luciferase driven by the 15 kb HO-1 promoter (HO-1/Luc Tg) had less increased light emission in hyperoxia compared with adults. Compared with adults, levels of the represser of HO-1 transcription, Bach1, were higher in the neonatal lung as was nuclear protein-DNA binding to the antioxidant response element (ARE) from HO-1. Furthermore, at baseline and in hyperoxia, chromatin immunoprecipitation (ChIP) revealed increased Bach1 binding to the HO-1 distal enhancers (DEs) in the neonates compared with adults. These data suggest that elevated levels of Bach1 may help to limit HO-1 induction in the newborn at baseline and in response to oxidative stress.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health