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

Abstract

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.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Michael Bauer
    • 1
  • 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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