title: Carbon monoxide: a vital signalling molecule and potent toxin in the myocardium.
abstract: Endogenous carbon monoxide (CO) is generated through the heme oxygenase-catalysed degradation of heme and is now established as an important, biologically active molecule capable of modulating a number of signalling pathways. Such pathways include those involving nitric oxide/guanylate cyclase, reactive oxygen species (ROS) and MAP kinases. In the heart, up-regulation of the inducible form of heme oxygenase (HO-1) following stresses such as ischemia/reperfusion provides cardioprotection, and much evidence indicates that CO accounts for many of these beneficial effects. One target of CO appears to be the L-type Ca(2+) channel; CO inhibits recombinant and native forms of this cardiac channel via mitochondria-derived ROS, which likely contributes to the protective effects of CO. In stark contrast, exposure to exogenous CO is toxic: chronic, low-level exposure can lead to myocardial injury and fibrosis, whereas acute exposure is associated with life-threatening arrhythmias. The molecular mechanisms accounting for such effects remain to be elucidated, but require future study before the potentially beneficial effects of CO therapy can be safely exploited. This article is part of a Special Issue entitled "Local Signaling in Myocytes".
authors.affiliation: Faculties of Medicine and Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. c.s.peers@leeds.ac.uk
authors.forename: Chris
authors.initials: C
authors.lastname: Peers
authors.forename: Derek S
authors.initials: DS
authors.lastname: Steele
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism* / Q000633:toxicity; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D007473:Ion Channels; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D020928:Mitogen-Activated Protein Kinases