Heme oxygenase-1/carbon monoxide: From metabolism to molecular therapy

Stefan W. Ryter, Augustine M.K. Choi

Research output: Contribution to journalReview articlepeer-review

223 Scopus citations

Abstract

Heme oxygenase-1 (HO-1), a ubiquitous inducible stress-response protein, serves a major metabolic function in heme turnover. HO activity cleaves hemeto form biliverdin-IXα, carbon monoxide (CO), and iron. Genetic experiments have revealed a central role for HO-1 in tissue homeostasis, protection against oxidative stress, and in the pathogenesis of disease. Four decades of research have witnessed not only progress in elucidating the molecular mechanisms underlying the regulation and function of this illustrious enzyme, but also haveopenedremarkable translational applications for HO-1 and its reaction products. CO, once regarded as a metabolic waste, can act as an endogenous mediator of cellular signaling and vascular function. Exogenous application of CO by inhalation or pharmacologic delivery can confer cytoprotection in preclinical models of lung/vascular injury and disease, based on anti-apoptotic, anti-inflammatory, and anti-proliferative properties. The bile pigments, biliverdin and bilirubin, end products of heme degradation, have also shown potential as therapeutics in vascular disease based on anti-inflammatory and anti-proliferative activities. Further translational and clinical trials research will unveil whether the HO-1 system or any of its reaction products can be successfully applied as molecular medicine in human disease.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume41
Issue number3
DOIs
StatePublished - Sep 1 2009

Keywords

  • Bilirubin
  • Carbon monoxide
  • Heme oxygenase-1
  • Lung injury

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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