SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response

Autores
Peixoto, Estanislao; Atorrasagasti, María Catalina; Malvicini, Mariana; Fiore, Esteban Juan; Rodriguez, Marcelo; García, Mariana Gabriela; Finocchieto, Paola; Poderoso, Juan José; Corrales, Fernando; Mazzolini Rizzo, Guillermo Daniel
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
SPARC, also known as osteonectin and BM-40, is a matricellular protein with a number of biological functions. Hepatic SPARC expression is induced in response to thioacetamide, bile-duct ligation, and acute injuries such as concanavalin A and lipopolysacharide (LPS)/D-galactosamine. We have previously demonstrated that the therapeutic inhibition of SPARC or SPARC gene deletion protected mice against liver injury. We investigated the mechanisms involved in the protective effect of SPARC inhibition in mice. We performed a proteome analysis of livers from SPARC+/+ and SPARC−/− mice chronically treated with thioacetamide. Catalase activity, carbonylation levels, oxidative stress response, and mitochondrial function were studied. Genomic analysis revealed that SPARC−/− mice had an increased expression of cell proliferation genes. Proteins involved in detoxification of reactive oxygen species such as catalase, peroxirredoxine-1, and glutathione-S-transferase P1 and Mu1 were highly expressed as evidenced by proteome analysis; hepatic catalase activity was increased in SPARC−/− mice. Oxidative stress response and carbonylation levels were lower in livers from SPARC−/− mice. Hepatic mitochondria showed lower levels of nitrogen reactive species in the SPARC−/− concanavalin A-treated mice. Mitochondrial morphology was preserved, and its complex activity reduced in SPARC−/− mice. In conclusion, our data suggest that the protection associated with SPARC gene deletion may be partially due to a higher proliferative capacity of hepatocytes and an enhanced oxidative stress defense in SPARC−/− mice after liver injury.
Fil: Peixoto, Estanislao. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Atorrasagasti, María Catalina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina
Fil: Fiore, Esteban Juan. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Marcelo. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina
Fil: Finocchieto, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Corrales, Fernando. Cima; España
Fil: Mazzolini Rizzo, Guillermo Daniel. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Sparc
Hepatocyte Proliferation
Liver Damage
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:11336/44928
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/44928
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress responsePeixoto, EstanislaoAtorrasagasti, María CatalinaMalvicini, MarianaFiore, Esteban JuanRodriguez, MarceloGarcía, Mariana GabrielaFinocchieto, PaolaPoderoso, Juan JoséCorrales, FernandoMazzolini Rizzo, Guillermo DanielSparcHepatocyte ProliferationLiver Damagehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3SPARC, also known as osteonectin and BM-40, is a matricellular protein with a number of biological functions. Hepatic SPARC expression is induced in response to thioacetamide, bile-duct ligation, and acute injuries such as concanavalin A and lipopolysacharide (LPS)/D-galactosamine. We have previously demonstrated that the therapeutic inhibition of SPARC or SPARC gene deletion protected mice against liver injury. We investigated the mechanisms involved in the protective effect of SPARC inhibition in mice. We performed a proteome analysis of livers from SPARC+/+ and SPARC−/− mice chronically treated with thioacetamide. Catalase activity, carbonylation levels, oxidative stress response, and mitochondrial function were studied. Genomic analysis revealed that SPARC−/− mice had an increased expression of cell proliferation genes. Proteins involved in detoxification of reactive oxygen species such as catalase, peroxirredoxine-1, and glutathione-S-transferase P1 and Mu1 were highly expressed as evidenced by proteome analysis; hepatic catalase activity was increased in SPARC−/− mice. Oxidative stress response and carbonylation levels were lower in livers from SPARC−/− mice. Hepatic mitochondria showed lower levels of nitrogen reactive species in the SPARC−/− concanavalin A-treated mice. Mitochondrial morphology was preserved, and its complex activity reduced in SPARC−/− mice. In conclusion, our data suggest that the protection associated with SPARC gene deletion may be partially due to a higher proliferative capacity of hepatocytes and an enhanced oxidative stress defense in SPARC−/− mice after liver injury.Fil: Peixoto, Estanislao. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Atorrasagasti, María Catalina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; ArgentinaFil: Fiore, Esteban Juan. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez, Marcelo. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; ArgentinaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; ArgentinaFil: Finocchieto, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Corrales, Fernando. Cima; EspañaFil: Mazzolini Rizzo, Guillermo Daniel. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaImpact Journals2016-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/44928Peixoto, Estanislao; Atorrasagasti, María Catalina; Malvicini, Mariana; Fiore, Esteban Juan; Rodriguez, Marcelo; et al.; SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response; Impact Journals; Oncotarget; 5-2016; 1-111949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=9456&path%5B%5D=29365info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.9456info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:35Zoai:ri.conicet.gov.ar:11336/44928instacron: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 09:49:35.26CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
title SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
spellingShingle SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
Peixoto, Estanislao
Sparc
Hepatocyte Proliferation
Liver Damage
title_short SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
title_full SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
title_fullStr SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
title_full_unstemmed SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
title_sort SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response
dc.creator.none.fl_str_mv Peixoto, Estanislao
Atorrasagasti, María Catalina
Malvicini, Mariana
Fiore, Esteban Juan
Rodriguez, Marcelo
García, Mariana Gabriela
Finocchieto, Paola
Poderoso, Juan José
Corrales, Fernando
Mazzolini Rizzo, Guillermo Daniel
author Peixoto, Estanislao
author_facet Peixoto, Estanislao
Atorrasagasti, María Catalina
Malvicini, Mariana
Fiore, Esteban Juan
Rodriguez, Marcelo
García, Mariana Gabriela
Finocchieto, Paola
Poderoso, Juan José
Corrales, Fernando
Mazzolini Rizzo, Guillermo Daniel
author_role author
author2 Atorrasagasti, María Catalina
Malvicini, Mariana
Fiore, Esteban Juan
Rodriguez, Marcelo
García, Mariana Gabriela
Finocchieto, Paola
Poderoso, Juan José
Corrales, Fernando
Mazzolini Rizzo, Guillermo Daniel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sparc
Hepatocyte Proliferation
Liver Damage
topic Sparc
Hepatocyte Proliferation
Liver Damage
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv SPARC, also known as osteonectin and BM-40, is a matricellular protein with a number of biological functions. Hepatic SPARC expression is induced in response to thioacetamide, bile-duct ligation, and acute injuries such as concanavalin A and lipopolysacharide (LPS)/D-galactosamine. We have previously demonstrated that the therapeutic inhibition of SPARC or SPARC gene deletion protected mice against liver injury. We investigated the mechanisms involved in the protective effect of SPARC inhibition in mice. We performed a proteome analysis of livers from SPARC+/+ and SPARC−/− mice chronically treated with thioacetamide. Catalase activity, carbonylation levels, oxidative stress response, and mitochondrial function were studied. Genomic analysis revealed that SPARC−/− mice had an increased expression of cell proliferation genes. Proteins involved in detoxification of reactive oxygen species such as catalase, peroxirredoxine-1, and glutathione-S-transferase P1 and Mu1 were highly expressed as evidenced by proteome analysis; hepatic catalase activity was increased in SPARC−/− mice. Oxidative stress response and carbonylation levels were lower in livers from SPARC−/− mice. Hepatic mitochondria showed lower levels of nitrogen reactive species in the SPARC−/− concanavalin A-treated mice. Mitochondrial morphology was preserved, and its complex activity reduced in SPARC−/− mice. In conclusion, our data suggest that the protection associated with SPARC gene deletion may be partially due to a higher proliferative capacity of hepatocytes and an enhanced oxidative stress defense in SPARC−/− mice after liver injury.
Fil: Peixoto, Estanislao. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Atorrasagasti, María Catalina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina
Fil: Fiore, Esteban Juan. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Marcelo. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina
Fil: Finocchieto, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Corrales, Fernando. Cima; España
Fil: Mazzolini Rizzo, Guillermo Daniel. Instituto de Investigaciones Médicas Aplicadas. Laboratorio de Terapia Génica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description SPARC, also known as osteonectin and BM-40, is a matricellular protein with a number of biological functions. Hepatic SPARC expression is induced in response to thioacetamide, bile-duct ligation, and acute injuries such as concanavalin A and lipopolysacharide (LPS)/D-galactosamine. We have previously demonstrated that the therapeutic inhibition of SPARC or SPARC gene deletion protected mice against liver injury. We investigated the mechanisms involved in the protective effect of SPARC inhibition in mice. We performed a proteome analysis of livers from SPARC+/+ and SPARC−/− mice chronically treated with thioacetamide. Catalase activity, carbonylation levels, oxidative stress response, and mitochondrial function were studied. Genomic analysis revealed that SPARC−/− mice had an increased expression of cell proliferation genes. Proteins involved in detoxification of reactive oxygen species such as catalase, peroxirredoxine-1, and glutathione-S-transferase P1 and Mu1 were highly expressed as evidenced by proteome analysis; hepatic catalase activity was increased in SPARC−/− mice. Oxidative stress response and carbonylation levels were lower in livers from SPARC−/− mice. Hepatic mitochondria showed lower levels of nitrogen reactive species in the SPARC−/− concanavalin A-treated mice. Mitochondrial morphology was preserved, and its complex activity reduced in SPARC−/− mice. In conclusion, our data suggest that the protection associated with SPARC gene deletion may be partially due to a higher proliferative capacity of hepatocytes and an enhanced oxidative stress defense in SPARC−/− mice after liver injury.
publishDate 2016
dc.date.none.fl_str_mv 2016-05
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/11336/44928
Peixoto, Estanislao; Atorrasagasti, María Catalina; Malvicini, Mariana; Fiore, Esteban Juan; Rodriguez, Marcelo; et al.; SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response; Impact Journals; Oncotarget; 5-2016; 1-11
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/44928
identifier_str_mv Peixoto, Estanislao; Atorrasagasti, María Catalina; Malvicini, Mariana; Fiore, Esteban Juan; Rodriguez, Marcelo; et al.; SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response; Impact Journals; Oncotarget; 5-2016; 1-11
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.9456
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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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
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dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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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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