title: Nitric oxide produced by cytochrome c oxidase helps stabilize HIF-1α in hypoxic mammalian cells.
abstract: The mitochondrial respiratory chain has been reported to play a role in the stabilization of HIF-1α when mammalian cells experience hypoxia, most likely through the generation of free radicals. Although previous studies have suggested the involvement of superoxide catalyzed by complex III more recent studies raise the possibility that nitric oxide (NO) catalyzed by cytochrome c oxidase (Cco/NO), which functions in hypoxic signaling in yeast, may also be involved. Herein, we have found that HEK293 cells, which do not express a NOS isoform, possess Cco/NO activity and that this activity is responsible for an increase in intracellular NO levels when these cells are exposed to hypoxia. By using PTIO, a NO scavenger, we have also found that the increased NO levels in hypoxic HEK293 cells help stabilize HIF-1α. These findings suggest a new mechanism for mitochondrial involvement in hypoxic signaling in mammalian cells.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
authors.forename: Kerri A
authors.initials: KA
authors.lastname: Ball
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Nelson
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Foster
authors.forename: Robert O
authors.initials: RO
authors.lastname: Poyton
mesh_terms: D015687:Cell Hypoxia; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D055550:Protein Stability
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007093:Imidazoles; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D003576:Electron Transport Complex IV