Unique oxidative mechanisms for the reactive nitrogen oxide species, nitroxyl anion

Katrina M Miranda, Michael G. Espey, Kenichi Yamada, Murali Krishna, Natalie Ludwick, Sungmee Kim, David Jourd'heuil, Matthew B. Grisham, Martin Feelisch, Jon M. Fukuto, David A. Wink

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

The nitroxyl anion (NO-) is a highly reactive molecule that may be involved in pathophysiological actions associated with increased formation of reactive nitrogen oxide species. Angeli's salt (Na2N2O3; AS) is a NO- donor that has been shown to exert marked cytotoxicity. However, its decomposition intermediates have not been well characterized. In this study, the chemical reactivity of AS was examined and compared with that of peroxynitrite (ONOO-) and NO/N2O3. Under aerobic conditions, AS and ONOO- exhibited similar and considerably higher affinities for dihydrorhodamine (DHR) than NO/N2O3. Quenching of DHR oxidation by azide and nitrosation of diaminonaphthalene were exclusively observed with NO/N2O3. Additional comparison of ONOO- and AS chemistry demonstrated that ONOO- was a far more potent one-electron oxidant and nitrating agent of hydroxyphenylacetic acid than was AS. However, AS was more effective at hydroxylating benzoic acid than was ONOO-. Taken together, these data indicate that neither NO/N2O3 nor ONOO- is an intermediate of AS decomposition. Evaluation of the stoichiometry of AS decomposition and O2 consumption revealed a 1:1 molar ratio. Indeed, oxidation of DHR mediated by AS proved to be oxygen-dependent. Analysis of the end products of AS decomposition demonstrated formation of NO2/- and NO3/- in approximately stoichiometric ratios. Several mechanisms are proposed for O2 adduct formation followed by decomposition to NO3/- or by oxidation of an HN2O3/- molecule to form NO2/-. Given that the cytotoxicity of AS is far greater than that of either NO/N2O3 or NO + O2/-, this study provides important new insights into the implications of the potential endogenous formation of NO- under inflammatory conditions in vivo.

Original languageEnglish (US)
Pages (from-to)1720-1727
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number3
DOIs
StatePublished - Jan 19 2001
Externally publishedYes

Fingerprint

Nitrosation
Reactive Nitrogen Species
Peroxynitrous Acid
Benzoic Acid
Azides
Oxidants
Anions
Nitric Oxide
Electrons
Oxygen
Decomposition
Acids
Cytotoxicity
Oxidation
Chemical reactivity
Molecules
Stoichiometry
Quenching
nitroxyl
oxyhyponitrite

ASJC Scopus subject areas

  • Biochemistry

Cite this

Unique oxidative mechanisms for the reactive nitrogen oxide species, nitroxyl anion. / Miranda, Katrina M; Espey, Michael G.; Yamada, Kenichi; Krishna, Murali; Ludwick, Natalie; Kim, Sungmee; Jourd'heuil, David; Grisham, Matthew B.; Feelisch, Martin; Fukuto, Jon M.; Wink, David A.

In: Journal of Biological Chemistry, Vol. 276, No. 3, 19.01.2001, p. 1720-1727.

Research output: Contribution to journalArticle

Miranda, KM, Espey, MG, Yamada, K, Krishna, M, Ludwick, N, Kim, S, Jourd'heuil, D, Grisham, MB, Feelisch, M, Fukuto, JM & Wink, DA 2001, 'Unique oxidative mechanisms for the reactive nitrogen oxide species, nitroxyl anion', Journal of Biological Chemistry, vol. 276, no. 3, pp. 1720-1727. https://doi.org/10.1074/jbc.M006174200
Miranda, Katrina M ; Espey, Michael G. ; Yamada, Kenichi ; Krishna, Murali ; Ludwick, Natalie ; Kim, Sungmee ; Jourd'heuil, David ; Grisham, Matthew B. ; Feelisch, Martin ; Fukuto, Jon M. ; Wink, David A. / Unique oxidative mechanisms for the reactive nitrogen oxide species, nitroxyl anion. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 3. pp. 1720-1727.
@article{8066b2dc906e4fcaa1fc6b78efbfae60,
title = "Unique oxidative mechanisms for the reactive nitrogen oxide species, nitroxyl anion",
abstract = "The nitroxyl anion (NO-) is a highly reactive molecule that may be involved in pathophysiological actions associated with increased formation of reactive nitrogen oxide species. Angeli's salt (Na2N2O3; AS) is a NO- donor that has been shown to exert marked cytotoxicity. However, its decomposition intermediates have not been well characterized. In this study, the chemical reactivity of AS was examined and compared with that of peroxynitrite (ONOO-) and NO/N2O3. Under aerobic conditions, AS and ONOO- exhibited similar and considerably higher affinities for dihydrorhodamine (DHR) than NO/N2O3. Quenching of DHR oxidation by azide and nitrosation of diaminonaphthalene were exclusively observed with NO/N2O3. Additional comparison of ONOO- and AS chemistry demonstrated that ONOO- was a far more potent one-electron oxidant and nitrating agent of hydroxyphenylacetic acid than was AS. However, AS was more effective at hydroxylating benzoic acid than was ONOO-. Taken together, these data indicate that neither NO/N2O3 nor ONOO- is an intermediate of AS decomposition. Evaluation of the stoichiometry of AS decomposition and O2 consumption revealed a 1:1 molar ratio. Indeed, oxidation of DHR mediated by AS proved to be oxygen-dependent. Analysis of the end products of AS decomposition demonstrated formation of NO2/- and NO3/- in approximately stoichiometric ratios. Several mechanisms are proposed for O2 adduct formation followed by decomposition to NO3/- or by oxidation of an HN2O3/- molecule to form NO2/-. Given that the cytotoxicity of AS is far greater than that of either NO/N2O3 or NO + O2/-, this study provides important new insights into the implications of the potential endogenous formation of NO- under inflammatory conditions in vivo.",
author = "Miranda, {Katrina M} and Espey, {Michael G.} and Kenichi Yamada and Murali Krishna and Natalie Ludwick and Sungmee Kim and David Jourd'heuil and Grisham, {Matthew B.} and Martin Feelisch and Fukuto, {Jon M.} and Wink, {David A.}",
year = "2001",
month = "1",
day = "19",
doi = "10.1074/jbc.M006174200",
language = "English (US)",
volume = "276",
pages = "1720--1727",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Unique oxidative mechanisms for the reactive nitrogen oxide species, nitroxyl anion

AU - Miranda, Katrina M

AU - Espey, Michael G.

AU - Yamada, Kenichi

AU - Krishna, Murali

AU - Ludwick, Natalie

AU - Kim, Sungmee

AU - Jourd'heuil, David

AU - Grisham, Matthew B.

AU - Feelisch, Martin

AU - Fukuto, Jon M.

AU - Wink, David A.

PY - 2001/1/19

Y1 - 2001/1/19

N2 - The nitroxyl anion (NO-) is a highly reactive molecule that may be involved in pathophysiological actions associated with increased formation of reactive nitrogen oxide species. Angeli's salt (Na2N2O3; AS) is a NO- donor that has been shown to exert marked cytotoxicity. However, its decomposition intermediates have not been well characterized. In this study, the chemical reactivity of AS was examined and compared with that of peroxynitrite (ONOO-) and NO/N2O3. Under aerobic conditions, AS and ONOO- exhibited similar and considerably higher affinities for dihydrorhodamine (DHR) than NO/N2O3. Quenching of DHR oxidation by azide and nitrosation of diaminonaphthalene were exclusively observed with NO/N2O3. Additional comparison of ONOO- and AS chemistry demonstrated that ONOO- was a far more potent one-electron oxidant and nitrating agent of hydroxyphenylacetic acid than was AS. However, AS was more effective at hydroxylating benzoic acid than was ONOO-. Taken together, these data indicate that neither NO/N2O3 nor ONOO- is an intermediate of AS decomposition. Evaluation of the stoichiometry of AS decomposition and O2 consumption revealed a 1:1 molar ratio. Indeed, oxidation of DHR mediated by AS proved to be oxygen-dependent. Analysis of the end products of AS decomposition demonstrated formation of NO2/- and NO3/- in approximately stoichiometric ratios. Several mechanisms are proposed for O2 adduct formation followed by decomposition to NO3/- or by oxidation of an HN2O3/- molecule to form NO2/-. Given that the cytotoxicity of AS is far greater than that of either NO/N2O3 or NO + O2/-, this study provides important new insights into the implications of the potential endogenous formation of NO- under inflammatory conditions in vivo.

AB - The nitroxyl anion (NO-) is a highly reactive molecule that may be involved in pathophysiological actions associated with increased formation of reactive nitrogen oxide species. Angeli's salt (Na2N2O3; AS) is a NO- donor that has been shown to exert marked cytotoxicity. However, its decomposition intermediates have not been well characterized. In this study, the chemical reactivity of AS was examined and compared with that of peroxynitrite (ONOO-) and NO/N2O3. Under aerobic conditions, AS and ONOO- exhibited similar and considerably higher affinities for dihydrorhodamine (DHR) than NO/N2O3. Quenching of DHR oxidation by azide and nitrosation of diaminonaphthalene were exclusively observed with NO/N2O3. Additional comparison of ONOO- and AS chemistry demonstrated that ONOO- was a far more potent one-electron oxidant and nitrating agent of hydroxyphenylacetic acid than was AS. However, AS was more effective at hydroxylating benzoic acid than was ONOO-. Taken together, these data indicate that neither NO/N2O3 nor ONOO- is an intermediate of AS decomposition. Evaluation of the stoichiometry of AS decomposition and O2 consumption revealed a 1:1 molar ratio. Indeed, oxidation of DHR mediated by AS proved to be oxygen-dependent. Analysis of the end products of AS decomposition demonstrated formation of NO2/- and NO3/- in approximately stoichiometric ratios. Several mechanisms are proposed for O2 adduct formation followed by decomposition to NO3/- or by oxidation of an HN2O3/- molecule to form NO2/-. Given that the cytotoxicity of AS is far greater than that of either NO/N2O3 or NO + O2/-, this study provides important new insights into the implications of the potential endogenous formation of NO- under inflammatory conditions in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0035910389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035910389&partnerID=8YFLogxK

U2 - 10.1074/jbc.M006174200

DO - 10.1074/jbc.M006174200

M3 - Article

C2 - 11042174

AN - SCOPUS:0035910389

VL - 276

SP - 1720

EP - 1727

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -