Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease

Autores
Wen, Jian Jun; Zago, María Paola; Nuñez, Sonia; Gupta, Shivali; Nuñez Burgos, Federico; Garg, Nisha Jain
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is initiated upon infection by Trypanosoma cruzi. Among the health consequences is a decline in heart function, and the pathophysiological mechanisms underlying this manifestation are not well understood. To explore the possible mechanisms, we employed IgY LC10 affinity chromatography in conjunction with ProteomeLab PF2D and two-dimensional gel electrophoresis (2D-GE) to resolve the proteome signature of high-abundance and low-abundance serum proteins in chagasic patients. MALDI-TOF MS/MS analysis yielded 80 and 14 differentially expressed proteins associated with cardiomyopathy of chagasic and other etiologies, respectively. The extent of oxidative stress-induced carbonyl modifications of the differentially expressed proteins (n=26) was increased and coupled with a depression of antioxidant proteins. Functional annotation of the top networks developed by Ingenuity Pathway Analysis of proteome database identified dysregulation of inflammation/acute phase response signaling and lipid metabolism relevant to production of prostaglandins and arachidonic acid in chagasic patients. Overlay of the major networks identified prothrombin and plasminogen at a nodal position with connectivity to proteome signature indicative of heart disease (i.e. thrombosis, angiogenesis, vasodilatation of blood vessels or the aorta, increased permeability of blood vessel and endothelial tubes), and inflammatory responses (e.g., platelet aggregation, complement activation, phagocytes activation and migration). The detection of cardiac proteins (myosin light chain 2, myosin heavy chain 11) and increased levels of vinculin and plasminogen provided a comprehensive set of biomarkers of cardiac muscle injury and development of clinical Chagas disease in human patients. These results provide an impetus for biomarker validation in large cohorts of clinically characterized chagasic patients
Fil: Wen, Jian Jun. University of Texas Medical Branch; Estados Unidos
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Nuñez, Sonia. Provincia de Salta. Hospital San Bernardo; Argentina
Fil: Gupta, Shivali. University of Texas Medical Branch; Estados Unidos
Fil: Nuñez Burgos, Federico. Provincia de Salta. Hospital San Bernardo; Argentina
Fil: Garg, Nisha Jain. University of Texas Medical Branch; Estados Unidos
Materia
BIOMARKER
CHAGAS DISEASE
OXIDATIVE STRESS
T. CRUZI
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:11336/29986
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of DiseaseWen, Jian JunZago, María PaolaNuñez, SoniaGupta, ShivaliNuñez Burgos, FedericoGarg, Nisha JainBIOMARKERCHAGAS DISEASEOXIDATIVE STRESST. CRUZIhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Chagas disease is initiated upon infection by Trypanosoma cruzi. Among the health consequences is a decline in heart function, and the pathophysiological mechanisms underlying this manifestation are not well understood. To explore the possible mechanisms, we employed IgY LC10 affinity chromatography in conjunction with ProteomeLab PF2D and two-dimensional gel electrophoresis (2D-GE) to resolve the proteome signature of high-abundance and low-abundance serum proteins in chagasic patients. MALDI-TOF MS/MS analysis yielded 80 and 14 differentially expressed proteins associated with cardiomyopathy of chagasic and other etiologies, respectively. The extent of oxidative stress-induced carbonyl modifications of the differentially expressed proteins (n=26) was increased and coupled with a depression of antioxidant proteins. Functional annotation of the top networks developed by Ingenuity Pathway Analysis of proteome database identified dysregulation of inflammation/acute phase response signaling and lipid metabolism relevant to production of prostaglandins and arachidonic acid in chagasic patients. Overlay of the major networks identified prothrombin and plasminogen at a nodal position with connectivity to proteome signature indicative of heart disease (i.e. thrombosis, angiogenesis, vasodilatation of blood vessels or the aorta, increased permeability of blood vessel and endothelial tubes), and inflammatory responses (e.g., platelet aggregation, complement activation, phagocytes activation and migration). The detection of cardiac proteins (myosin light chain 2, myosin heavy chain 11) and increased levels of vinculin and plasminogen provided a comprehensive set of biomarkers of cardiac muscle injury and development of clinical Chagas disease in human patients. These results provide an impetus for biomarker validation in large cohorts of clinically characterized chagasic patientsFil: Wen, Jian Jun. University of Texas Medical Branch; Estados UnidosFil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Nuñez, Sonia. Provincia de Salta. Hospital San Bernardo; ArgentinaFil: Gupta, Shivali. University of Texas Medical Branch; Estados UnidosFil: Nuñez Burgos, Federico. Provincia de Salta. Hospital San Bernardo; ArgentinaFil: Garg, Nisha Jain. University of Texas Medical Branch; Estados UnidosAmerican Society for Biochemistry and Molecular Biology2012-04info: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/11336/29986Wen, Jian Jun; Zago, María Paola; Nuñez, Sonia; Gupta, Shivali; Nuñez Burgos, Federico; et al.; Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease; American Society for Biochemistry and Molecular Biology; Molecular & Cellular Proteomics; 11; 4-2012; 435-4521535 94761535-9484CONICET DigitalCONICETenginfo:eu-repo/semantics/reference/url/http://www.mcponline.org/content/11/8/435info:eu-repo/semantics/altIdentifier/url/http://www.mcponline.org/content/11/8/435info:eu-repo/semantics/altIdentifier/doi/10.1074/mcp.M112.017640info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412973/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:07Zoai:ri.conicet.gov.ar:11336/29986instacron: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 09:36:07.561CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
title Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
spellingShingle Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
Wen, Jian Jun
BIOMARKER
CHAGAS DISEASE
OXIDATIVE STRESS
T. CRUZI
title_short Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
title_full Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
title_fullStr Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
title_full_unstemmed Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
title_sort Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease
dc.creator.none.fl_str_mv Wen, Jian Jun
Zago, María Paola
Nuñez, Sonia
Gupta, Shivali
Nuñez Burgos, Federico
Garg, Nisha Jain
author Wen, Jian Jun
author_facet Wen, Jian Jun
Zago, María Paola
Nuñez, Sonia
Gupta, Shivali
Nuñez Burgos, Federico
Garg, Nisha Jain
author_role author
author2 Zago, María Paola
Nuñez, Sonia
Gupta, Shivali
Nuñez Burgos, Federico
Garg, Nisha Jain
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv BIOMARKER
CHAGAS DISEASE
OXIDATIVE STRESS
T. CRUZI
topic BIOMARKER
CHAGAS DISEASE
OXIDATIVE STRESS
T. CRUZI
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chagas disease is initiated upon infection by Trypanosoma cruzi. Among the health consequences is a decline in heart function, and the pathophysiological mechanisms underlying this manifestation are not well understood. To explore the possible mechanisms, we employed IgY LC10 affinity chromatography in conjunction with ProteomeLab PF2D and two-dimensional gel electrophoresis (2D-GE) to resolve the proteome signature of high-abundance and low-abundance serum proteins in chagasic patients. MALDI-TOF MS/MS analysis yielded 80 and 14 differentially expressed proteins associated with cardiomyopathy of chagasic and other etiologies, respectively. The extent of oxidative stress-induced carbonyl modifications of the differentially expressed proteins (n=26) was increased and coupled with a depression of antioxidant proteins. Functional annotation of the top networks developed by Ingenuity Pathway Analysis of proteome database identified dysregulation of inflammation/acute phase response signaling and lipid metabolism relevant to production of prostaglandins and arachidonic acid in chagasic patients. Overlay of the major networks identified prothrombin and plasminogen at a nodal position with connectivity to proteome signature indicative of heart disease (i.e. thrombosis, angiogenesis, vasodilatation of blood vessels or the aorta, increased permeability of blood vessel and endothelial tubes), and inflammatory responses (e.g., platelet aggregation, complement activation, phagocytes activation and migration). The detection of cardiac proteins (myosin light chain 2, myosin heavy chain 11) and increased levels of vinculin and plasminogen provided a comprehensive set of biomarkers of cardiac muscle injury and development of clinical Chagas disease in human patients. These results provide an impetus for biomarker validation in large cohorts of clinically characterized chagasic patients
Fil: Wen, Jian Jun. University of Texas Medical Branch; Estados Unidos
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Nuñez, Sonia. Provincia de Salta. Hospital San Bernardo; Argentina
Fil: Gupta, Shivali. University of Texas Medical Branch; Estados Unidos
Fil: Nuñez Burgos, Federico. Provincia de Salta. Hospital San Bernardo; Argentina
Fil: Garg, Nisha Jain. University of Texas Medical Branch; Estados Unidos
description Chagas disease is initiated upon infection by Trypanosoma cruzi. Among the health consequences is a decline in heart function, and the pathophysiological mechanisms underlying this manifestation are not well understood. To explore the possible mechanisms, we employed IgY LC10 affinity chromatography in conjunction with ProteomeLab PF2D and two-dimensional gel electrophoresis (2D-GE) to resolve the proteome signature of high-abundance and low-abundance serum proteins in chagasic patients. MALDI-TOF MS/MS analysis yielded 80 and 14 differentially expressed proteins associated with cardiomyopathy of chagasic and other etiologies, respectively. The extent of oxidative stress-induced carbonyl modifications of the differentially expressed proteins (n=26) was increased and coupled with a depression of antioxidant proteins. Functional annotation of the top networks developed by Ingenuity Pathway Analysis of proteome database identified dysregulation of inflammation/acute phase response signaling and lipid metabolism relevant to production of prostaglandins and arachidonic acid in chagasic patients. Overlay of the major networks identified prothrombin and plasminogen at a nodal position with connectivity to proteome signature indicative of heart disease (i.e. thrombosis, angiogenesis, vasodilatation of blood vessels or the aorta, increased permeability of blood vessel and endothelial tubes), and inflammatory responses (e.g., platelet aggregation, complement activation, phagocytes activation and migration). The detection of cardiac proteins (myosin light chain 2, myosin heavy chain 11) and increased levels of vinculin and plasminogen provided a comprehensive set of biomarkers of cardiac muscle injury and development of clinical Chagas disease in human patients. These results provide an impetus for biomarker validation in large cohorts of clinically characterized chagasic patients
publishDate 2012
dc.date.none.fl_str_mv 2012-04
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/11336/29986
Wen, Jian Jun; Zago, María Paola; Nuñez, Sonia; Gupta, Shivali; Nuñez Burgos, Federico; et al.; Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease; American Society for Biochemistry and Molecular Biology; Molecular & Cellular Proteomics; 11; 4-2012; 435-452
1535 9476
1535-9484
CONICET Digital
CONICET
url http://hdl.handle.net/11336/29986
identifier_str_mv Wen, Jian Jun; Zago, María Paola; Nuñez, Sonia; Gupta, Shivali; Nuñez Burgos, Federico; et al.; Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease; American Society for Biochemistry and Molecular Biology; Molecular & Cellular Proteomics; 11; 4-2012; 435-452
1535 9476
1535-9484
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/reference/url/http://www.mcponline.org/content/11/8/435
info:eu-repo/semantics/altIdentifier/url/http://www.mcponline.org/content/11/8/435
info:eu-repo/semantics/altIdentifier/doi/10.1074/mcp.M112.017640
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412973/
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
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
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