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

Overview

MeSH Major

  • Carbon Monoxide
  • Genetic Therapy
  • Heme Oxygenase-1

abstract

  • Heme oxygenase-1 (HO-1), a ubiquitous inducible stress-response protein, serves a major metabolic function in heme turnover. HO activity cleaves heme to form biliverdin-IXalpha, 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 have opened remarkable 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.

publication date

  • September 2009

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC2742746

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2009-0170TR

PubMed ID

  • 19617398

Additional Document Info

start page

  • 251

end page

  • 60

volume

  • 41

number

  • 3