Myeloperoxidase-induced genomic DNA-centered radicals

Autores
Gomez-Mejiba, Sandra Esther; Zhai, Zili; Gimenez, Maria Sofia; Ashby, Michael T.; Chilakapati, Jaya; Kitchin, Kirk; Mason, Ronald P.; Ramirez, Dario
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis.
Fil: Gomez-Mejiba, Sandra Esther. Oklahoma Medical Research Foundation; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zhai, Zili. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Gimenez, Maria Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina
Fil: Ashby, Michael T.. University of Oklahoma; Estados Unidos
Fil: Chilakapati, Jaya. United States Environmental Protection Agency. National Health and Environmental Effects Research; Estados Unidos
Fil: Kitchin, Kirk. United States Environmental Protection Agency. National Health and Environmental Effects Research; Estados Unidos
Fil: Mason, Ronald P.. National Institutes of Health; Estados Unidos
Fil: Ramirez, Dario. Oklahoma Medical Research Foundation; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
DNA Damage
Epithelial cell
Inflammation
Mutagenesis mechanisms
Neutrophil
Reactive Oxygen Species (ROS)
DNA-centered radicals
Hypochlorous acid
Immuno-spin trapping
Myeloperoxidase
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:11336/14706
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/14706
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Myeloperoxidase-induced genomic DNA-centered radicalsGomez-Mejiba, Sandra EstherZhai, ZiliGimenez, Maria SofiaAshby, Michael T.Chilakapati, JayaKitchin, KirkMason, Ronald P.Ramirez, DarioDNA DamageEpithelial cellInflammationMutagenesis mechanismsNeutrophilReactive Oxygen Species (ROS)DNA-centered radicalsHypochlorous acidImmuno-spin trappingMyeloperoxidasehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis.Fil: Gomez-Mejiba, Sandra Esther. Oklahoma Medical Research Foundation; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zhai, Zili. Oklahoma Medical Research Foundation; Estados UnidosFil: Gimenez, Maria Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; ArgentinaFil: Ashby, Michael T.. University of Oklahoma; Estados UnidosFil: Chilakapati, Jaya. United States Environmental Protection Agency. National Health and Environmental Effects Research; Estados UnidosFil: Kitchin, Kirk. United States Environmental Protection Agency. National Health and Environmental Effects Research; Estados UnidosFil: Mason, Ronald P.. National Institutes of Health; Estados UnidosFil: Ramirez, Dario. Oklahoma Medical Research Foundation; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Society For Biochemistry And Molecular Biology2010-06info: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/11336/14706Gomez-Mejiba, Sandra Esther; Zhai, Zili; Gimenez, Maria Sofia; Ashby, Michael T.; Chilakapati, Jaya; et al.; Myeloperoxidase-induced genomic DNA-centered radicals; American Society For Biochemistry And Molecular Biology; Journal of Biological Chemistry; 285; 26; 6-2010; 20062-200710021-9258enginfo:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888418/info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M109.086579info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/285/26/20062info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:13:20Zoai:ri.conicet.gov.ar:11336/14706instacron: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 10:13:20.816CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Myeloperoxidase-induced genomic DNA-centered radicals
title Myeloperoxidase-induced genomic DNA-centered radicals
spellingShingle Myeloperoxidase-induced genomic DNA-centered radicals
Gomez-Mejiba, Sandra Esther
DNA Damage
Epithelial cell
Inflammation
Mutagenesis mechanisms
Neutrophil
Reactive Oxygen Species (ROS)
DNA-centered radicals
Hypochlorous acid
Immuno-spin trapping
Myeloperoxidase
title_short Myeloperoxidase-induced genomic DNA-centered radicals
title_full Myeloperoxidase-induced genomic DNA-centered radicals
title_fullStr Myeloperoxidase-induced genomic DNA-centered radicals
title_full_unstemmed Myeloperoxidase-induced genomic DNA-centered radicals
title_sort Myeloperoxidase-induced genomic DNA-centered radicals
dc.creator.none.fl_str_mv Gomez-Mejiba, Sandra Esther
Zhai, Zili
Gimenez, Maria Sofia
Ashby, Michael T.
Chilakapati, Jaya
Kitchin, Kirk
Mason, Ronald P.
Ramirez, Dario
author Gomez-Mejiba, Sandra Esther
author_facet Gomez-Mejiba, Sandra Esther
Zhai, Zili
Gimenez, Maria Sofia
Ashby, Michael T.
Chilakapati, Jaya
Kitchin, Kirk
Mason, Ronald P.
Ramirez, Dario
author_role author
author2 Zhai, Zili
Gimenez, Maria Sofia
Ashby, Michael T.
Chilakapati, Jaya
Kitchin, Kirk
Mason, Ronald P.
Ramirez, Dario
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA Damage
Epithelial cell
Inflammation
Mutagenesis mechanisms
Neutrophil
Reactive Oxygen Species (ROS)
DNA-centered radicals
Hypochlorous acid
Immuno-spin trapping
Myeloperoxidase
topic DNA Damage
Epithelial cell
Inflammation
Mutagenesis mechanisms
Neutrophil
Reactive Oxygen Species (ROS)
DNA-centered radicals
Hypochlorous acid
Immuno-spin trapping
Myeloperoxidase
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis.
Fil: Gomez-Mejiba, Sandra Esther. Oklahoma Medical Research Foundation; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zhai, Zili. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Gimenez, Maria Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina
Fil: Ashby, Michael T.. University of Oklahoma; Estados Unidos
Fil: Chilakapati, Jaya. United States Environmental Protection Agency. National Health and Environmental Effects Research; Estados Unidos
Fil: Kitchin, Kirk. United States Environmental Protection Agency. National Health and Environmental Effects Research; Estados Unidos
Fil: Mason, Ronald P.. National Institutes of Health; Estados Unidos
Fil: Ramirez, Dario. Oklahoma Medical Research Foundation; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis.
publishDate 2010
dc.date.none.fl_str_mv 2010-06
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/11336/14706
Gomez-Mejiba, Sandra Esther; Zhai, Zili; Gimenez, Maria Sofia; Ashby, Michael T.; Chilakapati, Jaya; et al.; Myeloperoxidase-induced genomic DNA-centered radicals; American Society For Biochemistry And Molecular Biology; Journal of Biological Chemistry; 285; 26; 6-2010; 20062-20071
0021-9258
url http://hdl.handle.net/11336/14706
identifier_str_mv Gomez-Mejiba, Sandra Esther; Zhai, Zili; Gimenez, Maria Sofia; Ashby, Michael T.; Chilakapati, Jaya; et al.; Myeloperoxidase-induced genomic DNA-centered radicals; American Society For Biochemistry And Molecular Biology; Journal of Biological Chemistry; 285; 26; 6-2010; 20062-20071
0021-9258
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888418/
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M109.086579
info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/285/26/20062
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_ 1844614050030288896
score 13.070432

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