title: Convergence of biological nitration and nitrosation via symmetrical nitrous anhydride.
abstract: The current perspective holds that the generation of secondary signaling mediators from nitrite (NO2(-)) requires acidification to nitrous acid (HNO2) or metal catalysis. Herein, the use of stable isotope-labeled NO2(-) and LC-MS/MS analysis of products reveals that NO2(-) also participates in fatty acid nitration and thiol S-nitrosation at neutral pH. These reactions occur in the absence of metal centers and are stimulated by autoxidation of nitric oxide ((•)NO) via the formation of symmetrical dinitrogen trioxide (nitrous anhydride, symN2O3). Although theoretical models have predicted physiological symN2O3 formation, its generation is now demonstrated in aqueous reaction systems, cell models and in vivo, with the concerted reactions of (•)NO and NO2(-) shown to be critical for symN2O3 formation. These results reveal new mechanisms underlying the NO2(-) propagation of (•)NO signaling and the regulation of both biomolecule function and signaling network activity via NO2(-)-dependent nitrosation and nitration reactions.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Dario A
authors.initials: DA
authors.lastname: Vitturi
authors.affiliation: Cátedra de Inmunología, Universidad de la República, Montevideo, Uruguay.
authors.forename: Lucia
authors.initials: L
authors.lastname: Minarrieta
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Salvatore
authors.affiliation: Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Postlethwait
authors.affiliation: 1] Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. [2] Fondazione Ri.MED, Palermo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fazzari
authors.affiliation: 1] Laboratorio de Fisicoquímica Biológica, Universidad de la República, Montevideo, Uruguay. [2] Center for Free Radical and Biomedical Research, Universidad de la República, Montevideo, Uruguay.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferrer-Sueta
authors.affiliation: 1] Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. [2] Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. [3] Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Lancaster
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Schopfer
mesh_terms: D000818:Animals; D002460:Cell Line; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007700:Kinetics; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000737:chemistry* / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D009587:Nitrogen Isotopes; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000378:metabolism; D015538:Nitrosation; D009608:Nitrous Acid / Q000737:chemistry* / Q000378:metabolism; D010103:Oxygen Isotopes
chemical_list: D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009587:Nitrogen Isotopes; D009589:Nitrogen Oxides; D010103:Oxygen Isotopes; C031701:nitrogen trioxide; D009569:Nitric Oxide; D005978:Glutathione; D009608:Nitrous Acid