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Sci. STKE, 27 April 2004
Vol. 2004, Issue 230, p. re6
[DOI: 10.1126/stke.2302004re6]

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Carbon Monoxide: To Boldly Go Where NO Has Gone Before

Stefan W. Ryter, Danielle Morse, and Augustine M. K. Choi*

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.

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-IXα. 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.

*Corresponding author. Phone, (412) 692-2117; fax, (412) 692-2260; e-mail, choiam{at}upmc.edu

Citation: S. W. Ryter, D. Morse, A. M. K. Choi, Carbon Monoxide: To Boldly Go Where NO Has Gone Before. Sci. STKE 2004, re6 (2004).

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