The heme oxygenase-carbon monoxide system: regulation and role in stress response and organ failure.
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.
Bauer
Michael
M
Department of Anesthesiology and Intensive Care Medicine, Friedrich Schiller University Hospital, Erlanger Allee 101, 07740, Jena, Germany. michael.bauer@med.uni-jena.de
Huse
Klaus
K
Settmacher
Utz
U
Claus
Ralf A
RA
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D016638:Critical Illness; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D012377:Rodentia
D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1