title: Cytochrome c oxidase regulates endogenous nitric oxide availability in respiring cells: a possible explanation for hypoxic vasodilation.
abstract: One of the many routes proposed for the cellular inactivation of endogenous nitric oxide (NO) is by the cytochrome c oxidase of the mitochondrial respiratory chain. We have studied this possibility in human embryonic kidney cells engineered to generate controlled amounts of NO. We have used visible light spectroscopy to monitor continuously the redox state of cytochrome c oxidase in an oxygen-tight chamber, at the same time as which we measure cell respiration and the concentrations of oxygen and NO. Pharmacological manipulation of cytochrome c oxidase indicates that this enzyme, when it is in turnover and in its oxidized state, inactivates physiological amounts of NO, thus regulating its intra- and extracellular concentrations. This inactivation is prevented by blocking the enzyme with inhibitors, including NO. Furthermore, when cells generating low concentrations of NO respire toward hypoxia, the redox state of cytochrome c oxidase changes from oxidized to reduced, leading to a decrease in NO inactivation. The resultant increase in NO concentration could explain hypoxic vasodilation.
authors.affiliation: The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Miriam
authors.initials: M
authors.lastname: Palacios-Callender
authors.forename: Veronica
authors.initials: V
authors.lastname: Hollis
authors.forename: Miriam
authors.initials: M
authors.lastname: Mitchison
authors.forename: Nanci
authors.initials: N
authors.lastname: Frakich
authors.forename: David
authors.initials: D
authors.lastname: Unitt
authors.forename: Salvador
authors.initials: S
authors.lastname: Moncada
mesh_terms: D015687:Cell Hypoxia; D002460:Cell Line; D019069:Cell Respiration; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D014664:Vasodilation
chemical_list: D009573:Nitrites; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D003576:Electron Transport Complex IV