title: Carbon monoxide: to boldly go where NO has gone before.
abstract: The discovery that nitric oxide (NO) has powerful vasoactive properties identical to those of endothelial-derived relaxing factor spawned a vast body of research investigating the physiological actions of small gas molecules. NO, which arises endogenously through the action of nitric oxide synthase (NOS) enzymes, is a highly reactive gas that plays important roles in the regulation of vascular and immune function. Carbon monoxide (CO), a similar yet much more chemically stable gas, occurs in nature as a product of the oxidation or combustion of organic materials. CO also arises in cells and tissues as a byproduct of heme oxygenase (HO) activity, which degrades heme to biliverdin-IXalpha. Like NO, CO acts as a vasorelaxant and may regulate other vascular functions such as platelet aggregation and smooth muscle proliferation. CO has also been implicated as a neurotransmitter in the central nervous system. HO-1, the inducible form of HO, confers cytoprotection against oxidative stress in vitro and in vivo. CO, when applied at low concentration, exerts potent cytoprotective effects mimicking those of HO-1 induction, including down-regulation of inflammation and suppression of apoptosis. Many of the effects of CO depend on the activation of guanylate cyclase, which generates guanosine 3',5'-monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) signaling pathways. This review highlights new advances in the interaction of CO with cellular signaling processes.
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, MUH 628 NW, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Ryter
authors.forename: Danielle
authors.initials: D
authors.lastname: Morse
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D009569:Nitric Oxide; D002248:Carbon Monoxide