title: Heme oxygenase in neonatal lung injury and repair.
abstract: CONCLUSIONS
  Premature and sick neonates are often exposed to high concentrations of oxygen, which results in lung injury and long-term adverse consequences. Nevertheless, neonates are more tolerant to hyperoxia than are adults. This may be, in part, explained by the high lung content of heme oxygenase-1 (HO-1), the rate-limiting enzyme in the degradation of heme and an important stress protein. The abundance of HO-1 dictates its cytoprotective and deleterious effects. Interestingly, in response to hyperoxia, lung HO-1 mRNA is not further up-regulated in neonates, suggesting that lung HO-1 gene expression is tightly regulated so as to optimize cytoprotection when faced with an oxidative stress such as hyperoxia.
  
  
  BACKGROUND
  In addition to the lack of induction of HO-1 mRNA, neonatal lung HO-1 protein is observed in the nucleus in neonatal mice exposed to hyperoxia but not in adults, which is further evidence for the developmental regulation of HO-1. Nuclear HO-1 had unique properties independent of its enzymatic activity. In addition, there has been increasing evidence that nuclear HO-1 contributes to cellular proliferation and malignant transformation in several human cancers.
  
  
  RESULTS
  Since HO-1 has dual effects in cytoprotection and cellular proliferation, the titration of HO-1 effects is critical to ensure beneficial actions against oxidative stress.
  
  
  CONCLUSIONS
  Much more has to be understood about the specific roles of HO-1 so as to manipulate its abundance and/or nuclear migration to maximize the therapeutic benefit of this pleiotropic protein in the neonatal lung.
authors.affiliation: Department of Pediatrics, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Dennery
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D055370:Lung Injury / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D051547:Heme Oxygenase-1