Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells

Autores
Da Silva, Mathieu; Jaggers, Grayson K.; Verstraeten, Sandra Viviana; Erlejman, Alejandra Giselle; Fraga, Cesar Guillermo; Oteiza, Patricia Isabel
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Procyanidins are oligomers of flavanol subunits present in large amounts in fruits and vegetables. Their consumption is associated with health benefits against colonic inflammation and colorectal cancer (CRC). Large procyanidins (with more than three subunits) are not absorbed by intestinal epithelial cells but could exert biological actions through their interactions with the cell membrane. This study investigated the capacity of hexameric procyanidins (Hex) to prevent oncogenic events initiated by deoxycholic acid (DCA), a secondary bile acid linked to the promotion of CRC. Hex interacted with Caco-2 cell membranes preferentially at the water–lipid interface. Hex (2.5–20 μM) inhibited DCA-triggered increase in cellular calcium, NADPH oxidase activation, and oxidant production. DCA promoted the activation of protein kinase B (Akt), of the mitogen-activated protein kinases ERK1/2 and p38, and of the downstream transcription factor AP-1. This activation was not triggered by calcium or oxidant increases. Hex caused a dose-dependent inhibition of DCA-mediated activation of all these signals. DCA also triggered alterations in the cell monolayer morphology and apoptotic cell death, events that were delayed by Hex. The capacity of large procyanidins to interact with the cell membrane and prevent those cell membrane-associated events can in part explain the beneficial effects of procyanidins on CRC.
Fil: Da Silva, Mathieu. University of California at Davis; Estados Unidos
Fil: Jaggers, Grayson K.. University of California at Davis; Estados Unidos
Fil: Verstraeten, Sandra Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Fraga, Cesar Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentina. University of California at Davis; Estados Unidos
Fil: Oteiza, Patricia Isabel. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Procyanidins
Flavonoids
Intestinal Epithelial Cells
Bile Acids
Free Radicals
Nadph Oxidase
Membrane
Mapk
Colorectal Cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/18183
Acceder
id CONICETDig_81214b776ccb9421d00eb70ac8546cbe
oai_identifier_str oai:ri.conicet.gov.ar:11336/18183
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cellsDa Silva, MathieuJaggers, Grayson K.Verstraeten, Sandra VivianaErlejman, Alejandra GiselleFraga, Cesar GuillermoOteiza, Patricia IsabelProcyanidinsFlavonoidsIntestinal Epithelial CellsBile AcidsFree RadicalsNadph OxidaseMembraneMapkColorectal Cancerhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Procyanidins are oligomers of flavanol subunits present in large amounts in fruits and vegetables. Their consumption is associated with health benefits against colonic inflammation and colorectal cancer (CRC). Large procyanidins (with more than three subunits) are not absorbed by intestinal epithelial cells but could exert biological actions through their interactions with the cell membrane. This study investigated the capacity of hexameric procyanidins (Hex) to prevent oncogenic events initiated by deoxycholic acid (DCA), a secondary bile acid linked to the promotion of CRC. Hex interacted with Caco-2 cell membranes preferentially at the water–lipid interface. Hex (2.5–20 μM) inhibited DCA-triggered increase in cellular calcium, NADPH oxidase activation, and oxidant production. DCA promoted the activation of protein kinase B (Akt), of the mitogen-activated protein kinases ERK1/2 and p38, and of the downstream transcription factor AP-1. This activation was not triggered by calcium or oxidant increases. Hex caused a dose-dependent inhibition of DCA-mediated activation of all these signals. DCA also triggered alterations in the cell monolayer morphology and apoptotic cell death, events that were delayed by Hex. The capacity of large procyanidins to interact with the cell membrane and prevent those cell membrane-associated events can in part explain the beneficial effects of procyanidins on CRC.Fil: Da Silva, Mathieu. University of California at Davis; Estados UnidosFil: Jaggers, Grayson K.. University of California at Davis; Estados UnidosFil: Verstraeten, Sandra Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Fraga, Cesar Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentina. University of California at Davis; Estados UnidosFil: Oteiza, Patricia Isabel. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Inc2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18183Da Silva, Mathieu; Jaggers, Grayson K.; Verstraeten, Sandra Viviana; Erlejman, Alejandra Giselle; Fraga, Cesar Guillermo; et al.; Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells; Elsevier Inc; Free Radical Biology and Medicine; 52; 1; 1-2012; 151-1590891-5849CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0891584911010653info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2011.10.436info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:54:20Zoai:ri.conicet.gov.ar:11336/18183instacron: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:34982025-11-12 09:54:20.646CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
title Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
spellingShingle Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
Da Silva, Mathieu
Procyanidins
Flavonoids
Intestinal Epithelial Cells
Bile Acids
Free Radicals
Nadph Oxidase
Membrane
Mapk
Colorectal Cancer
title_short Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
title_full Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
title_fullStr Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
title_full_unstemmed Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
title_sort Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells
dc.creator.none.fl_str_mv Da Silva, Mathieu
Jaggers, Grayson K.
Verstraeten, Sandra Viviana
Erlejman, Alejandra Giselle
Fraga, Cesar Guillermo
Oteiza, Patricia Isabel
author Da Silva, Mathieu
author_facet Da Silva, Mathieu
Jaggers, Grayson K.
Verstraeten, Sandra Viviana
Erlejman, Alejandra Giselle
Fraga, Cesar Guillermo
Oteiza, Patricia Isabel
author_role author
author2 Jaggers, Grayson K.
Verstraeten, Sandra Viviana
Erlejman, Alejandra Giselle
Fraga, Cesar Guillermo
Oteiza, Patricia Isabel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Procyanidins
Flavonoids
Intestinal Epithelial Cells
Bile Acids
Free Radicals
Nadph Oxidase
Membrane
Mapk
Colorectal Cancer
topic Procyanidins
Flavonoids
Intestinal Epithelial Cells
Bile Acids
Free Radicals
Nadph Oxidase
Membrane
Mapk
Colorectal Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Procyanidins are oligomers of flavanol subunits present in large amounts in fruits and vegetables. Their consumption is associated with health benefits against colonic inflammation and colorectal cancer (CRC). Large procyanidins (with more than three subunits) are not absorbed by intestinal epithelial cells but could exert biological actions through their interactions with the cell membrane. This study investigated the capacity of hexameric procyanidins (Hex) to prevent oncogenic events initiated by deoxycholic acid (DCA), a secondary bile acid linked to the promotion of CRC. Hex interacted with Caco-2 cell membranes preferentially at the water–lipid interface. Hex (2.5–20 μM) inhibited DCA-triggered increase in cellular calcium, NADPH oxidase activation, and oxidant production. DCA promoted the activation of protein kinase B (Akt), of the mitogen-activated protein kinases ERK1/2 and p38, and of the downstream transcription factor AP-1. This activation was not triggered by calcium or oxidant increases. Hex caused a dose-dependent inhibition of DCA-mediated activation of all these signals. DCA also triggered alterations in the cell monolayer morphology and apoptotic cell death, events that were delayed by Hex. The capacity of large procyanidins to interact with the cell membrane and prevent those cell membrane-associated events can in part explain the beneficial effects of procyanidins on CRC.
Fil: Da Silva, Mathieu. University of California at Davis; Estados Unidos
Fil: Jaggers, Grayson K.. University of California at Davis; Estados Unidos
Fil: Verstraeten, Sandra Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Fraga, Cesar Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentina. University of California at Davis; Estados Unidos
Fil: Oteiza, Patricia Isabel. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Procyanidins are oligomers of flavanol subunits present in large amounts in fruits and vegetables. Their consumption is associated with health benefits against colonic inflammation and colorectal cancer (CRC). Large procyanidins (with more than three subunits) are not absorbed by intestinal epithelial cells but could exert biological actions through their interactions with the cell membrane. This study investigated the capacity of hexameric procyanidins (Hex) to prevent oncogenic events initiated by deoxycholic acid (DCA), a secondary bile acid linked to the promotion of CRC. Hex interacted with Caco-2 cell membranes preferentially at the water–lipid interface. Hex (2.5–20 μM) inhibited DCA-triggered increase in cellular calcium, NADPH oxidase activation, and oxidant production. DCA promoted the activation of protein kinase B (Akt), of the mitogen-activated protein kinases ERK1/2 and p38, and of the downstream transcription factor AP-1. This activation was not triggered by calcium or oxidant increases. Hex caused a dose-dependent inhibition of DCA-mediated activation of all these signals. DCA also triggered alterations in the cell monolayer morphology and apoptotic cell death, events that were delayed by Hex. The capacity of large procyanidins to interact with the cell membrane and prevent those cell membrane-associated events can in part explain the beneficial effects of procyanidins on CRC.
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/11336/18183
Da Silva, Mathieu; Jaggers, Grayson K.; Verstraeten, Sandra Viviana; Erlejman, Alejandra Giselle; Fraga, Cesar Guillermo; et al.; Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells; Elsevier Inc; Free Radical Biology and Medicine; 52; 1; 1-2012; 151-159
0891-5849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18183
identifier_str_mv Da Silva, Mathieu; Jaggers, Grayson K.; Verstraeten, Sandra Viviana; Erlejman, Alejandra Giselle; Fraga, Cesar Guillermo; et al.; Large procyanidins prevent bile acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells; Elsevier Inc; Free Radical Biology and Medicine; 52; 1; 1-2012; 151-159
0891-5849
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0891584911010653
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2011.10.436
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc
publisher.none.fl_str_mv Elsevier Inc
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 13.24909

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