FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver

Autores
Parody, Juan Pablo; Ceballos Mancini, María Paula; Quiroga, Ariel Dario; Frances, Daniel Eleazar Antonio; Carnovale, Cristina Ester; Pisani, Gerardo B.; Alvarez, María de Luján; Carrillo, Maria Cristina
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: FoxO3a, a member of the FOXO family of transcription factors, is expressed in adult liver and modulates the expression of genes involved in apoptosis. FoxO3a is post-translationally regulated, negatively by PI3K/Akt and MAPK/Erk and positively by oxidative stress/JNK pathways. In previous works, we have demonstrated that interferon-α2b (IFN-α2b) induces apoptosis of hepatic preneoplastic foci through the production of reactive oxygen species (ROS). Aims: To investigate the post-translational signal events triggered by the oxidative stress induced by IFN-α2b and the modulation of FoxO3a transcriptional activity during these events in rat preneoplastic liver. Methods Adult male Wistar rats were subjected to a two-phase model of hepatocarcinogenesis. A group of animals received IFN-α2b and another group received IFN-α2b and ascorbic acid (ASC), by intraperitoneal injection. Lipid peroxidation, immunohistochemistry, immunoblotting, co-immunoprecipitation and sqRT-PCR assays were performed to explore the role of ROS, JNK, Akt, Erk, FoxO3a, β-catenin and PUMA in the IFN-α2b-mediated apoptotic mechanism. Results: In vivo IFN-α2b treatment induced endogenous production of ROS which activated JNK. IFN-α2b blocked the activation of Akt and Erk, avoiding FoxO3a activity repression. Activated JNK was responsible for the nuclear translocation and transcriptional activity of FoxO3a which positively modulated the expression of PUMA, a proapoptotic player. In addition, nuclear FoxO3a competed for the nuclear β-catenin associated to TCF, inhibiting the canonical Wnt signalling pathway. Conclusions: The data presented here propose a model in which in vivo IFN-α2b treatment induces nuclear translocation and transcriptional activity of FoxO3a, triggering the mitochondrial apoptotic pathway in hepatic preneoplastic foci.
Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Pisani, Gerardo B.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Materia
Foxo3a
Apoptosis
Interferon Alfa
Liver
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:11336/6101
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/6101
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liverParody, Juan PabloCeballos Mancini, María PaulaQuiroga, Ariel DarioFrances, Daniel Eleazar AntonioCarnovale, Cristina EsterPisani, Gerardo B.Alvarez, María de LujánCarrillo, Maria CristinaFoxo3aApoptosisInterferon AlfaLiverhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: FoxO3a, a member of the FOXO family of transcription factors, is expressed in adult liver and modulates the expression of genes involved in apoptosis. FoxO3a is post-translationally regulated, negatively by PI3K/Akt and MAPK/Erk and positively by oxidative stress/JNK pathways. In previous works, we have demonstrated that interferon-α2b (IFN-α2b) induces apoptosis of hepatic preneoplastic foci through the production of reactive oxygen species (ROS). Aims: To investigate the post-translational signal events triggered by the oxidative stress induced by IFN-α2b and the modulation of FoxO3a transcriptional activity during these events in rat preneoplastic liver. Methods Adult male Wistar rats were subjected to a two-phase model of hepatocarcinogenesis. A group of animals received IFN-α2b and another group received IFN-α2b and ascorbic acid (ASC), by intraperitoneal injection. Lipid peroxidation, immunohistochemistry, immunoblotting, co-immunoprecipitation and sqRT-PCR assays were performed to explore the role of ROS, JNK, Akt, Erk, FoxO3a, β-catenin and PUMA in the IFN-α2b-mediated apoptotic mechanism. Results: In vivo IFN-α2b treatment induced endogenous production of ROS which activated JNK. IFN-α2b blocked the activation of Akt and Erk, avoiding FoxO3a activity repression. Activated JNK was responsible for the nuclear translocation and transcriptional activity of FoxO3a which positively modulated the expression of PUMA, a proapoptotic player. In addition, nuclear FoxO3a competed for the nuclear β-catenin associated to TCF, inhibiting the canonical Wnt signalling pathway. Conclusions: The data presented here propose a model in which in vivo IFN-α2b treatment induces nuclear translocation and transcriptional activity of FoxO3a, triggering the mitochondrial apoptotic pathway in hepatic preneoplastic foci.Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Pisani, Gerardo B.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaWiley2014-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6101Parody, Juan Pablo; Ceballos Mancini, María Paula; Quiroga, Ariel Dario; Frances, Daniel Eleazar Antonio; Carnovale, Cristina Ester; et al.; FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver; Wiley; Liver International; 34; 11-2014; 1566-15771478-3223enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/liv.12421/abstractinfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1111/liv.12421info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:27:49Zoai:ri.conicet.gov.ar:11336/6101instacron: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 10:27:50.143CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
title FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
spellingShingle FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
Parody, Juan Pablo
Foxo3a
Apoptosis
Interferon Alfa
Liver
title_short FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
title_full FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
title_fullStr FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
title_full_unstemmed FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
title_sort FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver
dc.creator.none.fl_str_mv Parody, Juan Pablo
Ceballos Mancini, María Paula
Quiroga, Ariel Dario
Frances, Daniel Eleazar Antonio
Carnovale, Cristina Ester
Pisani, Gerardo B.
Alvarez, María de Luján
Carrillo, Maria Cristina
author Parody, Juan Pablo
author_facet Parody, Juan Pablo
Ceballos Mancini, María Paula
Quiroga, Ariel Dario
Frances, Daniel Eleazar Antonio
Carnovale, Cristina Ester
Pisani, Gerardo B.
Alvarez, María de Luján
Carrillo, Maria Cristina
author_role author
author2 Ceballos Mancini, María Paula
Quiroga, Ariel Dario
Frances, Daniel Eleazar Antonio
Carnovale, Cristina Ester
Pisani, Gerardo B.
Alvarez, María de Luján
Carrillo, Maria Cristina
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Foxo3a
Apoptosis
Interferon Alfa
Liver
topic Foxo3a
Apoptosis
Interferon Alfa
Liver
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: FoxO3a, a member of the FOXO family of transcription factors, is expressed in adult liver and modulates the expression of genes involved in apoptosis. FoxO3a is post-translationally regulated, negatively by PI3K/Akt and MAPK/Erk and positively by oxidative stress/JNK pathways. In previous works, we have demonstrated that interferon-α2b (IFN-α2b) induces apoptosis of hepatic preneoplastic foci through the production of reactive oxygen species (ROS). Aims: To investigate the post-translational signal events triggered by the oxidative stress induced by IFN-α2b and the modulation of FoxO3a transcriptional activity during these events in rat preneoplastic liver. Methods Adult male Wistar rats were subjected to a two-phase model of hepatocarcinogenesis. A group of animals received IFN-α2b and another group received IFN-α2b and ascorbic acid (ASC), by intraperitoneal injection. Lipid peroxidation, immunohistochemistry, immunoblotting, co-immunoprecipitation and sqRT-PCR assays were performed to explore the role of ROS, JNK, Akt, Erk, FoxO3a, β-catenin and PUMA in the IFN-α2b-mediated apoptotic mechanism. Results: In vivo IFN-α2b treatment induced endogenous production of ROS which activated JNK. IFN-α2b blocked the activation of Akt and Erk, avoiding FoxO3a activity repression. Activated JNK was responsible for the nuclear translocation and transcriptional activity of FoxO3a which positively modulated the expression of PUMA, a proapoptotic player. In addition, nuclear FoxO3a competed for the nuclear β-catenin associated to TCF, inhibiting the canonical Wnt signalling pathway. Conclusions: The data presented here propose a model in which in vivo IFN-α2b treatment induces nuclear translocation and transcriptional activity of FoxO3a, triggering the mitochondrial apoptotic pathway in hepatic preneoplastic foci.
Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Pisani, Gerardo B.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
description Background: FoxO3a, a member of the FOXO family of transcription factors, is expressed in adult liver and modulates the expression of genes involved in apoptosis. FoxO3a is post-translationally regulated, negatively by PI3K/Akt and MAPK/Erk and positively by oxidative stress/JNK pathways. In previous works, we have demonstrated that interferon-α2b (IFN-α2b) induces apoptosis of hepatic preneoplastic foci through the production of reactive oxygen species (ROS). Aims: To investigate the post-translational signal events triggered by the oxidative stress induced by IFN-α2b and the modulation of FoxO3a transcriptional activity during these events in rat preneoplastic liver. Methods Adult male Wistar rats were subjected to a two-phase model of hepatocarcinogenesis. A group of animals received IFN-α2b and another group received IFN-α2b and ascorbic acid (ASC), by intraperitoneal injection. Lipid peroxidation, immunohistochemistry, immunoblotting, co-immunoprecipitation and sqRT-PCR assays were performed to explore the role of ROS, JNK, Akt, Erk, FoxO3a, β-catenin and PUMA in the IFN-α2b-mediated apoptotic mechanism. Results: In vivo IFN-α2b treatment induced endogenous production of ROS which activated JNK. IFN-α2b blocked the activation of Akt and Erk, avoiding FoxO3a activity repression. Activated JNK was responsible for the nuclear translocation and transcriptional activity of FoxO3a which positively modulated the expression of PUMA, a proapoptotic player. In addition, nuclear FoxO3a competed for the nuclear β-catenin associated to TCF, inhibiting the canonical Wnt signalling pathway. Conclusions: The data presented here propose a model in which in vivo IFN-α2b treatment induces nuclear translocation and transcriptional activity of FoxO3a, triggering the mitochondrial apoptotic pathway in hepatic preneoplastic foci.
publishDate 2014
dc.date.none.fl_str_mv 2014-11
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/11336/6101
Parody, Juan Pablo; Ceballos Mancini, María Paula; Quiroga, Ariel Dario; Frances, Daniel Eleazar Antonio; Carnovale, Cristina Ester; et al.; FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver; Wiley; Liver International; 34; 11-2014; 1566-1577
1478-3223
url http://hdl.handle.net/11336/6101
identifier_str_mv Parody, Juan Pablo; Ceballos Mancini, María Paula; Quiroga, Ariel Dario; Frances, Daniel Eleazar Antonio; Carnovale, Cristina Ester; et al.; FoxO3a modulation and promotion of apoptosis by interferon-alfa2b in rat preneoplastic liver; Wiley; Liver International; 34; 11-2014; 1566-1577
1478-3223
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/liv.12421/abstract
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1111/liv.12421
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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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