Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine

Autores
Salvatore, Sonia Rosana; Vitturi, Dario A.; Baker, Paul R. S.; Bonacci, Gustavo Roberto; Koenitzer, Jeffrey R.; Woodcock, Steven R.; Freeman, Bruce A.; Schopfer, Francisco J.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca- 9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 + 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and co-elution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with HgCl2. This reaction increases the level of free nitroalkene fraction >10-fold and displays a KD of 7.5x10-6 M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive non-invasive index of metabolic and inflammatory status.
Fil: Salvatore, Sonia Rosana. University of Pittsburgh; Estados Unidos
Fil: Vitturi, Dario A.. University of Pittsburgh; Estados Unidos
Fil: Baker, Paul R. S.. University of Pittsburgh; Estados Unidos
Fil: Bonacci, Gustavo Roberto. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Koenitzer, Jeffrey R.. University of Pittsburgh; Estados Unidos
Fil: Woodcock, Steven R.. University of Pittsburgh; Estados Unidos
Fil: Freeman, Bruce A.. University of Pittsburgh; Estados Unidos
Fil: Schopfer, Francisco J.. University of Pittsburgh; Estados Unidos
Materia
NITRO-FATTY ACID
NITRATION
ELECTROPHILE
MICHAEL ADDITION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25897
Acceder
id CONICETDig_677101cbfd24358f73e6947a717d1d31
oai_identifier_str oai:ri.conicet.gov.ar:11336/25897
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urineSalvatore, Sonia RosanaVitturi, Dario A.Baker, Paul R. S.Bonacci, Gustavo RobertoKoenitzer, Jeffrey R.Woodcock, Steven R.Freeman, Bruce A.Schopfer, Francisco J.NITRO-FATTY ACIDNITRATIONELECTROPHILEMICHAEL ADDITIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca- 9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 + 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and co-elution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with HgCl2. This reaction increases the level of free nitroalkene fraction >10-fold and displays a KD of 7.5x10-6 M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive non-invasive index of metabolic and inflammatory status.Fil: Salvatore, Sonia Rosana. University of Pittsburgh; Estados UnidosFil: Vitturi, Dario A.. University of Pittsburgh; Estados UnidosFil: Baker, Paul R. S.. University of Pittsburgh; Estados UnidosFil: Bonacci, Gustavo Roberto. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Koenitzer, Jeffrey R.. University of Pittsburgh; Estados UnidosFil: Woodcock, Steven R.. University of Pittsburgh; Estados UnidosFil: Freeman, Bruce A.. University of Pittsburgh; Estados UnidosFil: Schopfer, Francisco J.. University of Pittsburgh; Estados UnidosAmerican Society for Biochemistry and Molecular Biology2013-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25897Salvatore, Sonia Rosana; Vitturi, Dario A.; Baker, Paul R. S.; Bonacci, Gustavo Roberto; Koenitzer, Jeffrey R.; et al.; Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine; American Society for Biochemistry and Molecular Biology; Jlr Papers In Press; 54; 7; 4-2013; 1998-20090022-22751539-7262CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M037804info:eu-repo/semantics/altIdentifier/url/http://www.jlr.org/content/54/7/1998.longinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679401/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:09:33Zoai:ri.conicet.gov.ar:11336/25897instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:09:33.747CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
title Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
spellingShingle Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
Salvatore, Sonia Rosana
NITRO-FATTY ACID
NITRATION
ELECTROPHILE
MICHAEL ADDITION
title_short Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
title_full Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
title_fullStr Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
title_full_unstemmed Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
title_sort Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine
dc.creator.none.fl_str_mv Salvatore, Sonia Rosana
Vitturi, Dario A.
Baker, Paul R. S.
Bonacci, Gustavo Roberto
Koenitzer, Jeffrey R.
Woodcock, Steven R.
Freeman, Bruce A.
Schopfer, Francisco J.
author Salvatore, Sonia Rosana
author_facet Salvatore, Sonia Rosana
Vitturi, Dario A.
Baker, Paul R. S.
Bonacci, Gustavo Roberto
Koenitzer, Jeffrey R.
Woodcock, Steven R.
Freeman, Bruce A.
Schopfer, Francisco J.
author_role author
author2 Vitturi, Dario A.
Baker, Paul R. S.
Bonacci, Gustavo Roberto
Koenitzer, Jeffrey R.
Woodcock, Steven R.
Freeman, Bruce A.
Schopfer, Francisco J.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NITRO-FATTY ACID
NITRATION
ELECTROPHILE
MICHAEL ADDITION
topic NITRO-FATTY ACID
NITRATION
ELECTROPHILE
MICHAEL ADDITION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca- 9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 + 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and co-elution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with HgCl2. This reaction increases the level of free nitroalkene fraction >10-fold and displays a KD of 7.5x10-6 M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive non-invasive index of metabolic and inflammatory status.
Fil: Salvatore, Sonia Rosana. University of Pittsburgh; Estados Unidos
Fil: Vitturi, Dario A.. University of Pittsburgh; Estados Unidos
Fil: Baker, Paul R. S.. University of Pittsburgh; Estados Unidos
Fil: Bonacci, Gustavo Roberto. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Koenitzer, Jeffrey R.. University of Pittsburgh; Estados Unidos
Fil: Woodcock, Steven R.. University of Pittsburgh; Estados Unidos
Fil: Freeman, Bruce A.. University of Pittsburgh; Estados Unidos
Fil: Schopfer, Francisco J.. University of Pittsburgh; Estados Unidos
description The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca- 9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 + 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and co-elution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with HgCl2. This reaction increases the level of free nitroalkene fraction >10-fold and displays a KD of 7.5x10-6 M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive non-invasive index of metabolic and inflammatory status.
publishDate 2013
dc.date.none.fl_str_mv 2013-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25897
Salvatore, Sonia Rosana; Vitturi, Dario A.; Baker, Paul R. S.; Bonacci, Gustavo Roberto; Koenitzer, Jeffrey R.; et al.; Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine; American Society for Biochemistry and Molecular Biology; Jlr Papers In Press; 54; 7; 4-2013; 1998-2009
0022-2275
1539-7262
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25897
identifier_str_mv Salvatore, Sonia Rosana; Vitturi, Dario A.; Baker, Paul R. S.; Bonacci, Gustavo Roberto; Koenitzer, Jeffrey R.; et al.; Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine; American Society for Biochemistry and Molecular Biology; Jlr Papers In Press; 54; 7; 4-2013; 1998-2009
0022-2275
1539-7262
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M037804
info:eu-repo/semantics/altIdentifier/url/http://www.jlr.org/content/54/7/1998.long
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679401/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613975578247168
score 13.070432

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