Intensive Care Medicine

, Volume 34, Issue 4, pp 640–648 | Cite as

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

  • Michael BauerEmail author
  • Klaus Huse
  • Utz Settmacher
  • Ralf A. Claus
Mini Series: Basic research-related topics


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.


Nitric Oxide Heme Oxygenase Biliverdin BKCa Channel Bile Pigment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer-Verlag 2008

Authors and Affiliations

  • Michael Bauer
    • 1
    Email author
  • Klaus Huse
    • 2
  • Utz Settmacher
    • 3
  • Ralf A. Claus
    • 1
  1. 1.Department of Anesthesiology and Intensive Care MedicineFriedrich Schiller University HospitalJenaGermany
  2. 2.Leibniz Institute for Age Research – Fritz Lipmann InstituteJenaGermany
  3. 3.Department of General, Visceral, and Vascular SurgeryFriedrich Schiller University HospitalJenaGermany

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