Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications

Stefan W. Ryter, Jawed Alam, Augustine M.K. Choi

Research output: Contribution to journalReview articlepeer-review

2012 Scopus citations

Abstract

The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO). In recent years, endogenously produced CO has been shown to possess intriguing signaling properties affecting numerous critical cellular functions including but not limited to inflammation, cellular proliferation, and apoptotic cell death. The era of gaseous molecules in biomedical research and human diseases initiated with the discovery that the endothelial cell-derived relaxing factor was identical to the gaseous molecule nitric oxide (NO). The discovery that endogenously produced gaseous molecules such as NO and now CO can impart potent physiological and biological effector functions truly represented a paradigm shift and unraveled new avenues of intense investigations. This review covers the molecular and biochemical characterization of HOs, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress. Furthermore, the current understanding of the functional significance of HO shall be discussed from the perspective of each of the metabolic by-products, with a special emphasis on CO. Finally, this presentation aspires to lay a foundation for potential future clinical applications of these systems.

Original languageEnglish (US)
Pages (from-to)583-650
Number of pages68
JournalPhysiological Reviews
Volume86
Issue number2
DOIs
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications'. Together they form a unique fingerprint.

Cite this