Bach1 Modulates Heme Oxygenase-1 Expression in the Neonatal Mouse Lung

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-I 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-tmRNA compared with adults. To better understand the differential response of lung HO-I to hyperoxia. we exposed newborn and adult mice to > 95% oxygen. The newborn kings had reduced HO-1 mRNA induction compared with adults and newborn transgenic mice overexpressing 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 repressor 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 Bach I binding to file HO-1 distal enhancers (DEs) in the neonates compared with adults. These data suggest that elevated levels of Bach1 may help to limit HO-I induction in the newborn at baseline and in response to oxidative stress. (Pediatr Res 65: 145-149, 2009)