The heme oxygenase-carbon monoxide system: regulation and role in stress response and organ failure

Intensive Care Med. 2008 Apr;34(4):640-8. doi: 10.1007/s00134-008-1010-2. Epub 2008 Feb 20.


Heme oxygenase (HO) breaks down heme, the iron-containing, oxygen-carrying constituent of red blood cells, yielding biliverdin, iron (II) ions, and carbon monoxide (CO). Among the isoenzymes cloned to date, only HO-1 can be induced by a panoply of stimuli linked by their ability to provoke oxidative stress. HO-1 induction protects against cell death in experimental models associated with ischemia/reperfusion or inflammation, making the gene a promising target for critical care medicine. Induction of HO-1 may confer protection by controlling intracellular levels of toxic heme, or by anti-inflammatory, anti-apoptotic, and blood flow-maintaining effects of its by-products biliverdin and CO. Although protective effects of upregulation of HO-1 have been reported for a variety of cells and tissues, evidence suggests that the protective action may be restricted to a rather narrow threshold of overexpression. In addition, there is substantial variation in gene expression depending on transcriptional control mechanisms such as a microsatellite length polymorphism. Genetic variability and the required use of cytotoxic inducers are hurdles for purposeful targeting of HO-1 gene expression in critical care, while administration of by-products of the pathway seems feasible at present.

Publication types

  • Review

MeSH terms

  • Animals
  • Carbon Monoxide / metabolism*
  • Critical Illness
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic*
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1 / genetics*
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Oxidative Stress*
  • Rodentia


  • Carbon Monoxide
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1