Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells

Autores
Chisari, Andrea Nancy; Sancho, Patricia; Caja, Laia; Bertran, Esther; Fabregat, Isabel
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Protein malnutrition occurs when there is insufficient protein to meet metabolic demands. Previous works have indicated that cycles of protein fasting/refeeding enhance the incidence of early lesions during chemical carcinogenesis in rat liver. The general objective of this work was to study the effect of aminoacids (Aa) deprivation on the proliferation and survival of hepatocytes, to understand its possible involvement in the generation of pre-neoplastic stages in the liver. Lack of Aa in the culture medium of an immortalized mice hepatocyte cell line induced loss in cell viability, correlating with apoptosis. However, a subpopulation of cells was able to survive, which showed a more proliferative phenotype and resistance to apoptotic stimuli. Escaping to Aa deprivation-induced death is coincident with an activated mTOR signaling and higher levels of phospho-AKT and phospho-ERKs, which correlated with increased activation of EGFR/SRC pathway and overexpression of EGFR ligands, such as TGF-α and HB-EGF. Lack of Aa induced a rapid increase in reactive oxygen species (ROS) production. However, cells that survived showed an enhancement in the levels of reduced glutathione and a higher expression of γ-GCS, the regulatory enzyme of glutathione synthesis, which can be interpreted as an adaptation of the cells to counteract the oxidative stress. In conclusion, results presented in this paper indicate that it is possible to isolate a subpopulation of hepatocytes that are able to grow in the absence of Aa, showing higher capacity to proliferate and survive, reminiscent of a preneoplastic phenotype.
Fil: Chisari, Andrea Nancy. L'Hospitalet de Llobregat; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina
Fil: Sancho, Patricia. L'Hospitalet de Llobregat; España
Fil: Caja, Laia. L'Hospitalet de Llobregat; España
Fil: Bertran, Esther. L'Hospitalet de Llobregat; España
Fil: Fabregat, Isabel. L'Hospitalet de Llobregat; España. Universidad de Barcelona; España
Materia
Aminoacids
Hepatocyte Proliferation
Apoptosis
Reactive Oxygen Species
Low Protein Diet
Liver Carcinogenesis
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:11336/13049
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/13049
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cellsChisari, Andrea NancySancho, PatriciaCaja, LaiaBertran, EstherFabregat, IsabelAminoacidsHepatocyte ProliferationApoptosisReactive Oxygen SpeciesLow Protein DietLiver Carcinogenesishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Protein malnutrition occurs when there is insufficient protein to meet metabolic demands. Previous works have indicated that cycles of protein fasting/refeeding enhance the incidence of early lesions during chemical carcinogenesis in rat liver. The general objective of this work was to study the effect of aminoacids (Aa) deprivation on the proliferation and survival of hepatocytes, to understand its possible involvement in the generation of pre-neoplastic stages in the liver. Lack of Aa in the culture medium of an immortalized mice hepatocyte cell line induced loss in cell viability, correlating with apoptosis. However, a subpopulation of cells was able to survive, which showed a more proliferative phenotype and resistance to apoptotic stimuli. Escaping to Aa deprivation-induced death is coincident with an activated mTOR signaling and higher levels of phospho-AKT and phospho-ERKs, which correlated with increased activation of EGFR/SRC pathway and overexpression of EGFR ligands, such as TGF-α and HB-EGF. Lack of Aa induced a rapid increase in reactive oxygen species (ROS) production. However, cells that survived showed an enhancement in the levels of reduced glutathione and a higher expression of γ-GCS, the regulatory enzyme of glutathione synthesis, which can be interpreted as an adaptation of the cells to counteract the oxidative stress. In conclusion, results presented in this paper indicate that it is possible to isolate a subpopulation of hepatocytes that are able to grow in the absence of Aa, showing higher capacity to proliferate and survive, reminiscent of a preneoplastic phenotype.Fil: Chisari, Andrea Nancy. L'Hospitalet de Llobregat; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; ArgentinaFil: Sancho, Patricia. L'Hospitalet de Llobregat; EspañaFil: Caja, Laia. L'Hospitalet de Llobregat; EspañaFil: Bertran, Esther. L'Hospitalet de Llobregat; EspañaFil: Fabregat, Isabel. L'Hospitalet de Llobregat; España. Universidad de Barcelona; EspañaElsevier Inc2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13049Chisari, Andrea Nancy; Sancho, Patricia; Caja, Laia; Bertran, Esther; Fabregat, Isabel; Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells; Elsevier Inc; Cellular Signalling; 24; 1; 1-2012; 325-3320898-6568enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0898656811002993info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cellsig.2011.09.018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:52:33Zoai:ri.conicet.gov.ar:11336/13049instacron: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 09:52:33.619CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
title Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
spellingShingle Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
Chisari, Andrea Nancy
Aminoacids
Hepatocyte Proliferation
Apoptosis
Reactive Oxygen Species
Low Protein Diet
Liver Carcinogenesis
title_short Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
title_full Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
title_fullStr Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
title_full_unstemmed Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
title_sort Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells
dc.creator.none.fl_str_mv Chisari, Andrea Nancy
Sancho, Patricia
Caja, Laia
Bertran, Esther
Fabregat, Isabel
author Chisari, Andrea Nancy
author_facet Chisari, Andrea Nancy
Sancho, Patricia
Caja, Laia
Bertran, Esther
Fabregat, Isabel
author_role author
author2 Sancho, Patricia
Caja, Laia
Bertran, Esther
Fabregat, Isabel
author2_role author
author
author
author
dc.subject.none.fl_str_mv Aminoacids
Hepatocyte Proliferation
Apoptosis
Reactive Oxygen Species
Low Protein Diet
Liver Carcinogenesis
topic Aminoacids
Hepatocyte Proliferation
Apoptosis
Reactive Oxygen Species
Low Protein Diet
Liver Carcinogenesis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Protein malnutrition occurs when there is insufficient protein to meet metabolic demands. Previous works have indicated that cycles of protein fasting/refeeding enhance the incidence of early lesions during chemical carcinogenesis in rat liver. The general objective of this work was to study the effect of aminoacids (Aa) deprivation on the proliferation and survival of hepatocytes, to understand its possible involvement in the generation of pre-neoplastic stages in the liver. Lack of Aa in the culture medium of an immortalized mice hepatocyte cell line induced loss in cell viability, correlating with apoptosis. However, a subpopulation of cells was able to survive, which showed a more proliferative phenotype and resistance to apoptotic stimuli. Escaping to Aa deprivation-induced death is coincident with an activated mTOR signaling and higher levels of phospho-AKT and phospho-ERKs, which correlated with increased activation of EGFR/SRC pathway and overexpression of EGFR ligands, such as TGF-α and HB-EGF. Lack of Aa induced a rapid increase in reactive oxygen species (ROS) production. However, cells that survived showed an enhancement in the levels of reduced glutathione and a higher expression of γ-GCS, the regulatory enzyme of glutathione synthesis, which can be interpreted as an adaptation of the cells to counteract the oxidative stress. In conclusion, results presented in this paper indicate that it is possible to isolate a subpopulation of hepatocytes that are able to grow in the absence of Aa, showing higher capacity to proliferate and survive, reminiscent of a preneoplastic phenotype.
Fil: Chisari, Andrea Nancy. L'Hospitalet de Llobregat; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina
Fil: Sancho, Patricia. L'Hospitalet de Llobregat; España
Fil: Caja, Laia. L'Hospitalet de Llobregat; España
Fil: Bertran, Esther. L'Hospitalet de Llobregat; España
Fil: Fabregat, Isabel. L'Hospitalet de Llobregat; España. Universidad de Barcelona; España
description Protein malnutrition occurs when there is insufficient protein to meet metabolic demands. Previous works have indicated that cycles of protein fasting/refeeding enhance the incidence of early lesions during chemical carcinogenesis in rat liver. The general objective of this work was to study the effect of aminoacids (Aa) deprivation on the proliferation and survival of hepatocytes, to understand its possible involvement in the generation of pre-neoplastic stages in the liver. Lack of Aa in the culture medium of an immortalized mice hepatocyte cell line induced loss in cell viability, correlating with apoptosis. However, a subpopulation of cells was able to survive, which showed a more proliferative phenotype and resistance to apoptotic stimuli. Escaping to Aa deprivation-induced death is coincident with an activated mTOR signaling and higher levels of phospho-AKT and phospho-ERKs, which correlated with increased activation of EGFR/SRC pathway and overexpression of EGFR ligands, such as TGF-α and HB-EGF. Lack of Aa induced a rapid increase in reactive oxygen species (ROS) production. However, cells that survived showed an enhancement in the levels of reduced glutathione and a higher expression of γ-GCS, the regulatory enzyme of glutathione synthesis, which can be interpreted as an adaptation of the cells to counteract the oxidative stress. In conclusion, results presented in this paper indicate that it is possible to isolate a subpopulation of hepatocytes that are able to grow in the absence of Aa, showing higher capacity to proliferate and survive, reminiscent of a preneoplastic phenotype.
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/11336/13049
Chisari, Andrea Nancy; Sancho, Patricia; Caja, Laia; Bertran, Esther; Fabregat, Isabel; Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells; Elsevier Inc; Cellular Signalling; 24; 1; 1-2012; 325-332
0898-6568
url http://hdl.handle.net/11336/13049
identifier_str_mv Chisari, Andrea Nancy; Sancho, Patricia; Caja, Laia; Bertran, Esther; Fabregat, Isabel; Lack of amino acids in mouse hepatocytes in culture induces the selection of preneoplastic cells; Elsevier Inc; Cellular Signalling; 24; 1; 1-2012; 325-332
0898-6568
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/S0898656811002993
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cellsig.2011.09.018
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
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 13.070432

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