Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis

Autores
Dhiman, Monisha; Zago, María Paola; Nuñez, Sonia; Amoroso, Alejandro; Rementeria, Hugo; Dousset, Pierre; Nuñez Burgos Dopazo, Federico Martìn; Garg, Nisha Jain
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trypanosoma cruzi elicits reactive oxygen species (ROS) of inflammatory and mitochondrial origin in infected hosts. In this study, we examined ROS-induced oxidative modifications in the heart and determined whether the resultant oxidized cardiac proteins are targets of immune response and of pathological significance in Chagas disease. Heart biopsies from chagasic mice, rats and human patients exhibited, when compared to those from normal controls, a substantial increase in protein 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), carbonyl, and 3-nitrotyrosine (3-NT) adducts. To evaluate whether oxidized proteins gain antigenic properties, heart homogenates or isolated cardiomyocytes were oxidized in vitro and one- or two-dimensional gel electrophoresis (2D-GE)/Western blotting (WB) was performed to investigate the proteomic oxidative changes and recognition of oxidized proteins by sera antibodies in chagasic rodents (mice, rats) and human patients. Human cardiomyocytes exhibited LD 50 sensitivity to 30 μM 4-HNE and 100 μM H 2O 2 at 6 h and 12 h, respectively. In vitro oxidation with 4-HNE or H 2O 2 resulted in a substantial increase in 4-HNE- and carbonyl-modified proteins that correlated with increased recognition of cardiac (cardiomyocytes) proteins by sera antibodies of chagasic rodents and human patients. 2D-GE/Western blotting followed by MALDI-TOF-MS/MS analysis to identify cardiac proteins that were oxidized and recognized by human chagasic sera yielded 82 unique proteins. We validated the 2D-GE results by enzyme-linked immunosorbent assay (ELISA) and WB and demonstrated that oxidation of recombinant titin enhanced its immunogenicity and recognition by sera antibodies from chagasic hosts (rats and humans). Treatment of infected rats with phenyl-α-tert-butyl nitrone (PBN, antioxidant) resulted in normalized immune detection of cardiac proteins associated with control of cardiac pathology and preservation of heart contractile function in chagasic rats. We conclude that ROS-induced, cardiac-oxidized antigens are targets of immune recognition by antibodies and molecular determinants for pathogenesis during Chagas disease.
Fil: Dhiman, Monisha. University of Texas Medical Branch; Estados Unidos
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
Fil: Nuñez, Sonia. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Amoroso, Alejandro. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Rementeria, Hugo. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Dousset, Pierre. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Nuñez Burgos Dopazo, Federico Martìn. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Garg, Nisha Jain. University of Texas Medical Branch; Estados Unidos
Materia
CHAGAS DESEASE
OXIDATIVE STRESS
PATHOGENESIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/9427
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/9427
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesisDhiman, MonishaZago, María PaolaNuñez, SoniaAmoroso, AlejandroRementeria, HugoDousset, PierreNuñez Burgos Dopazo, Federico MartìnGarg, Nisha JainCHAGAS DESEASEOXIDATIVE STRESSPATHOGENESIShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Trypanosoma cruzi elicits reactive oxygen species (ROS) of inflammatory and mitochondrial origin in infected hosts. In this study, we examined ROS-induced oxidative modifications in the heart and determined whether the resultant oxidized cardiac proteins are targets of immune response and of pathological significance in Chagas disease. Heart biopsies from chagasic mice, rats and human patients exhibited, when compared to those from normal controls, a substantial increase in protein 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), carbonyl, and 3-nitrotyrosine (3-NT) adducts. To evaluate whether oxidized proteins gain antigenic properties, heart homogenates or isolated cardiomyocytes were oxidized in vitro and one- or two-dimensional gel electrophoresis (2D-GE)/Western blotting (WB) was performed to investigate the proteomic oxidative changes and recognition of oxidized proteins by sera antibodies in chagasic rodents (mice, rats) and human patients. Human cardiomyocytes exhibited LD 50 sensitivity to 30 μM 4-HNE and 100 μM H 2O 2 at 6 h and 12 h, respectively. In vitro oxidation with 4-HNE or H 2O 2 resulted in a substantial increase in 4-HNE- and carbonyl-modified proteins that correlated with increased recognition of cardiac (cardiomyocytes) proteins by sera antibodies of chagasic rodents and human patients. 2D-GE/Western blotting followed by MALDI-TOF-MS/MS analysis to identify cardiac proteins that were oxidized and recognized by human chagasic sera yielded 82 unique proteins. We validated the 2D-GE results by enzyme-linked immunosorbent assay (ELISA) and WB and demonstrated that oxidation of recombinant titin enhanced its immunogenicity and recognition by sera antibodies from chagasic hosts (rats and humans). Treatment of infected rats with phenyl-α-tert-butyl nitrone (PBN, antioxidant) resulted in normalized immune detection of cardiac proteins associated with control of cardiac pathology and preservation of heart contractile function in chagasic rats. We conclude that ROS-induced, cardiac-oxidized antigens are targets of immune recognition by antibodies and molecular determinants for pathogenesis during Chagas disease.Fil: Dhiman, Monisha. University of Texas Medical Branch; Estados UnidosFil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; ArgentinaFil: Nuñez, Sonia. Hospital Público de Gestión Descentralizada San Bernardo; ArgentinaFil: Amoroso, Alejandro. Hospital Público de Gestión Descentralizada San Bernardo; ArgentinaFil: Rementeria, Hugo. Hospital Público de Gestión Descentralizada San Bernardo; ArgentinaFil: Dousset, Pierre. Hospital Público de Gestión Descentralizada San Bernardo; ArgentinaFil: Nuñez Burgos Dopazo, Federico Martìn. Hospital Público de Gestión Descentralizada San Bernardo; ArgentinaFil: Garg, Nisha Jain. University of Texas Medical Branch; Estados UnidosPublic Library of Science2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/9427Dhiman, Monisha; Zago, María Paola; Nuñez, Sonia; Amoroso, Alejandro; Rementeria, Hugo; et al.; Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis; Public Library of Science; Plos One; 7; 1; 1-2012; 1-131932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0028449info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028449info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22238578/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:51Zoai:ri.conicet.gov.ar:11336/9427instacron: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 09:33:51.985CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
title Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
spellingShingle Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
Dhiman, Monisha
CHAGAS DESEASE
OXIDATIVE STRESS
PATHOGENESIS
title_short Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
title_full Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
title_fullStr Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
title_full_unstemmed Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
title_sort Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis
dc.creator.none.fl_str_mv Dhiman, Monisha
Zago, María Paola
Nuñez, Sonia
Amoroso, Alejandro
Rementeria, Hugo
Dousset, Pierre
Nuñez Burgos Dopazo, Federico Martìn
Garg, Nisha Jain
author Dhiman, Monisha
author_facet Dhiman, Monisha
Zago, María Paola
Nuñez, Sonia
Amoroso, Alejandro
Rementeria, Hugo
Dousset, Pierre
Nuñez Burgos Dopazo, Federico Martìn
Garg, Nisha Jain
author_role author
author2 Zago, María Paola
Nuñez, Sonia
Amoroso, Alejandro
Rementeria, Hugo
Dousset, Pierre
Nuñez Burgos Dopazo, Federico Martìn
Garg, Nisha Jain
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHAGAS DESEASE
OXIDATIVE STRESS
PATHOGENESIS
topic CHAGAS DESEASE
OXIDATIVE STRESS
PATHOGENESIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Trypanosoma cruzi elicits reactive oxygen species (ROS) of inflammatory and mitochondrial origin in infected hosts. In this study, we examined ROS-induced oxidative modifications in the heart and determined whether the resultant oxidized cardiac proteins are targets of immune response and of pathological significance in Chagas disease. Heart biopsies from chagasic mice, rats and human patients exhibited, when compared to those from normal controls, a substantial increase in protein 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), carbonyl, and 3-nitrotyrosine (3-NT) adducts. To evaluate whether oxidized proteins gain antigenic properties, heart homogenates or isolated cardiomyocytes were oxidized in vitro and one- or two-dimensional gel electrophoresis (2D-GE)/Western blotting (WB) was performed to investigate the proteomic oxidative changes and recognition of oxidized proteins by sera antibodies in chagasic rodents (mice, rats) and human patients. Human cardiomyocytes exhibited LD 50 sensitivity to 30 μM 4-HNE and 100 μM H 2O 2 at 6 h and 12 h, respectively. In vitro oxidation with 4-HNE or H 2O 2 resulted in a substantial increase in 4-HNE- and carbonyl-modified proteins that correlated with increased recognition of cardiac (cardiomyocytes) proteins by sera antibodies of chagasic rodents and human patients. 2D-GE/Western blotting followed by MALDI-TOF-MS/MS analysis to identify cardiac proteins that were oxidized and recognized by human chagasic sera yielded 82 unique proteins. We validated the 2D-GE results by enzyme-linked immunosorbent assay (ELISA) and WB and demonstrated that oxidation of recombinant titin enhanced its immunogenicity and recognition by sera antibodies from chagasic hosts (rats and humans). Treatment of infected rats with phenyl-α-tert-butyl nitrone (PBN, antioxidant) resulted in normalized immune detection of cardiac proteins associated with control of cardiac pathology and preservation of heart contractile function in chagasic rats. We conclude that ROS-induced, cardiac-oxidized antigens are targets of immune recognition by antibodies and molecular determinants for pathogenesis during Chagas disease.
Fil: Dhiman, Monisha. University of Texas Medical Branch; Estados Unidos
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
Fil: Nuñez, Sonia. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Amoroso, Alejandro. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Rementeria, Hugo. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Dousset, Pierre. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Nuñez Burgos Dopazo, Federico Martìn. Hospital Público de Gestión Descentralizada San Bernardo; Argentina
Fil: Garg, Nisha Jain. University of Texas Medical Branch; Estados Unidos
description Trypanosoma cruzi elicits reactive oxygen species (ROS) of inflammatory and mitochondrial origin in infected hosts. In this study, we examined ROS-induced oxidative modifications in the heart and determined whether the resultant oxidized cardiac proteins are targets of immune response and of pathological significance in Chagas disease. Heart biopsies from chagasic mice, rats and human patients exhibited, when compared to those from normal controls, a substantial increase in protein 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), carbonyl, and 3-nitrotyrosine (3-NT) adducts. To evaluate whether oxidized proteins gain antigenic properties, heart homogenates or isolated cardiomyocytes were oxidized in vitro and one- or two-dimensional gel electrophoresis (2D-GE)/Western blotting (WB) was performed to investigate the proteomic oxidative changes and recognition of oxidized proteins by sera antibodies in chagasic rodents (mice, rats) and human patients. Human cardiomyocytes exhibited LD 50 sensitivity to 30 μM 4-HNE and 100 μM H 2O 2 at 6 h and 12 h, respectively. In vitro oxidation with 4-HNE or H 2O 2 resulted in a substantial increase in 4-HNE- and carbonyl-modified proteins that correlated with increased recognition of cardiac (cardiomyocytes) proteins by sera antibodies of chagasic rodents and human patients. 2D-GE/Western blotting followed by MALDI-TOF-MS/MS analysis to identify cardiac proteins that were oxidized and recognized by human chagasic sera yielded 82 unique proteins. We validated the 2D-GE results by enzyme-linked immunosorbent assay (ELISA) and WB and demonstrated that oxidation of recombinant titin enhanced its immunogenicity and recognition by sera antibodies from chagasic hosts (rats and humans). Treatment of infected rats with phenyl-α-tert-butyl nitrone (PBN, antioxidant) resulted in normalized immune detection of cardiac proteins associated with control of cardiac pathology and preservation of heart contractile function in chagasic rats. We conclude that ROS-induced, cardiac-oxidized antigens are targets of immune recognition by antibodies and molecular determinants for pathogenesis during Chagas disease.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/9427
Dhiman, Monisha; Zago, María Paola; Nuñez, Sonia; Amoroso, Alejandro; Rementeria, Hugo; et al.; Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis; Public Library of Science; Plos One; 7; 1; 1-2012; 1-13
1932-6203
url http://hdl.handle.net/11336/9427
identifier_str_mv Dhiman, Monisha; Zago, María Paola; Nuñez, Sonia; Amoroso, Alejandro; Rementeria, Hugo; et al.; Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis; Public Library of Science; Plos One; 7; 1; 1-2012; 1-13
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0028449
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028449
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22238578/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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
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score 13.070432

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