Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells

Autores
Costantino, Valeria Victoria; Gil Lorenzo, Andrea Fernanda; Lopez Appiolaza, Carlos Martìn; Cacciamani, Valeria; Benardon, María Eugenia; Bocanegra, María Victoria; Garramuño, Patricia
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Angiotensin II/Angiotensin II type 1 receptor (AT1R) effects are dependent on ROS production stimulated by NADPH oxidase activation. Hsp70 regulates a diverse set of signaling pathways through their interactions with proteins. CHIP is a E3 ubiquitin ligase that targets proteins for polyubiquitination and degradation. Aim: We study whether Hsp70/CHIP contribute to the negative regulation of Nox4 after AT1R blockage. Methods/Results: Primary culture of proximal tubule epithelial cells (PTCs) from SHR and WKY were stimulated with Angiotensin II (AII) or treated with Losartan (L) or Losartan plus Angiotensin II (L+AII). Losartan decreased AT1R and Nox4 while enhancing caveolin-1 and Hsp70 protein expression in SHR PTCs. Immunoprecipitation and immunofluorescence proved interaction and colocalization of increased Hsp70/CHIP with decreased Nox4 in SHR PTCs (L) vs (All). Hsp72 knockdown resulted in enhanced Nox4 protein levels, NADPH oxidase activity and ROS generation in (L+AII) revealing that Losartan was unable to abrogate AII effects on Nox4 expression and oxidative activity. Moreover, MG132 exposed PTCs (L) demostrated blocked ubiquitinated Nox4 degradation and increased colocalization of Nox4/Ubiquitin by inmunofluorescence. Conversely, Hsp72 depletion reduced Nox4/Ubiquitin colocalization causing Nox4 upregulation due to proteosomal degradation inhibition, although Losartan treatment. Conclusion: Our study demonstrates that Hsp70 and CHIP mediates the ubiquitination and proteasomal degradation of Nox4 as part ofthe antioxidative effect of Losartan in SHR.
Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Lopez Appiolaza, Carlos Martìn. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
Fil: Bocanegra, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Materia
ANGIOTENSIN II
LOSARTAN
NOX4/HSP70/CHIP
PROXIMAL TUBULE CELLS
UBIQUITINATION
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:11336/126805
Acceder
id CONICETDig_dab908bb73db3233a3762aebffb2c01c
oai_identifier_str oai:ri.conicet.gov.ar:11336/126805
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cellsCostantino, Valeria VictoriaGil Lorenzo, Andrea FernandaLopez Appiolaza, Carlos MartìnCacciamani, ValeriaBenardon, María EugeniaBocanegra, María VictoriaGarramuño, PatriciaANGIOTENSIN IILOSARTANNOX4/HSP70/CHIPPROXIMAL TUBULE CELLSUBIQUITINATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Angiotensin II/Angiotensin II type 1 receptor (AT1R) effects are dependent on ROS production stimulated by NADPH oxidase activation. Hsp70 regulates a diverse set of signaling pathways through their interactions with proteins. CHIP is a E3 ubiquitin ligase that targets proteins for polyubiquitination and degradation. Aim: We study whether Hsp70/CHIP contribute to the negative regulation of Nox4 after AT1R blockage. Methods/Results: Primary culture of proximal tubule epithelial cells (PTCs) from SHR and WKY were stimulated with Angiotensin II (AII) or treated with Losartan (L) or Losartan plus Angiotensin II (L+AII). Losartan decreased AT1R and Nox4 while enhancing caveolin-1 and Hsp70 protein expression in SHR PTCs. Immunoprecipitation and immunofluorescence proved interaction and colocalization of increased Hsp70/CHIP with decreased Nox4 in SHR PTCs (L) vs (All). Hsp72 knockdown resulted in enhanced Nox4 protein levels, NADPH oxidase activity and ROS generation in (L+AII) revealing that Losartan was unable to abrogate AII effects on Nox4 expression and oxidative activity. Moreover, MG132 exposed PTCs (L) demostrated blocked ubiquitinated Nox4 degradation and increased colocalization of Nox4/Ubiquitin by inmunofluorescence. Conversely, Hsp72 depletion reduced Nox4/Ubiquitin colocalization causing Nox4 upregulation due to proteosomal degradation inhibition, although Losartan treatment. Conclusion: Our study demonstrates that Hsp70 and CHIP mediates the ubiquitination and proteasomal degradation of Nox4 as part ofthe antioxidative effect of Losartan in SHR.Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Lopez Appiolaza, Carlos Martìn. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; ArgentinaFil: Bocanegra, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaKarger2015-08info: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/11336/126805Costantino, Valeria Victoria; Gil Lorenzo, Andrea Fernanda; Lopez Appiolaza, Carlos Martìn; Cacciamani, Valeria; Benardon, María Eugenia; et al.; Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells; Karger; Cellular Physiology and Biochemistry; 36; 6; 8-2015; 2183-21971015-8987CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/FullText/430184info:eu-repo/semantics/altIdentifier/doi/10.1159/000430184info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:23Zoai:ri.conicet.gov.ar:11336/126805instacron: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:34982025-09-03 09:43:23.99CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
title Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
spellingShingle Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
Costantino, Valeria Victoria
ANGIOTENSIN II
LOSARTAN
NOX4/HSP70/CHIP
PROXIMAL TUBULE CELLS
UBIQUITINATION
title_short Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
title_full Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
title_fullStr Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
title_full_unstemmed Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
title_sort Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
dc.creator.none.fl_str_mv Costantino, Valeria Victoria
Gil Lorenzo, Andrea Fernanda
Lopez Appiolaza, Carlos Martìn
Cacciamani, Valeria
Benardon, María Eugenia
Bocanegra, María Victoria
Garramuño, Patricia
author Costantino, Valeria Victoria
author_facet Costantino, Valeria Victoria
Gil Lorenzo, Andrea Fernanda
Lopez Appiolaza, Carlos Martìn
Cacciamani, Valeria
Benardon, María Eugenia
Bocanegra, María Victoria
Garramuño, Patricia
author_role author
author2 Gil Lorenzo, Andrea Fernanda
Lopez Appiolaza, Carlos Martìn
Cacciamani, Valeria
Benardon, María Eugenia
Bocanegra, María Victoria
Garramuño, Patricia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOTENSIN II
LOSARTAN
NOX4/HSP70/CHIP
PROXIMAL TUBULE CELLS
UBIQUITINATION
topic ANGIOTENSIN II
LOSARTAN
NOX4/HSP70/CHIP
PROXIMAL TUBULE CELLS
UBIQUITINATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Angiotensin II/Angiotensin II type 1 receptor (AT1R) effects are dependent on ROS production stimulated by NADPH oxidase activation. Hsp70 regulates a diverse set of signaling pathways through their interactions with proteins. CHIP is a E3 ubiquitin ligase that targets proteins for polyubiquitination and degradation. Aim: We study whether Hsp70/CHIP contribute to the negative regulation of Nox4 after AT1R blockage. Methods/Results: Primary culture of proximal tubule epithelial cells (PTCs) from SHR and WKY were stimulated with Angiotensin II (AII) or treated with Losartan (L) or Losartan plus Angiotensin II (L+AII). Losartan decreased AT1R and Nox4 while enhancing caveolin-1 and Hsp70 protein expression in SHR PTCs. Immunoprecipitation and immunofluorescence proved interaction and colocalization of increased Hsp70/CHIP with decreased Nox4 in SHR PTCs (L) vs (All). Hsp72 knockdown resulted in enhanced Nox4 protein levels, NADPH oxidase activity and ROS generation in (L+AII) revealing that Losartan was unable to abrogate AII effects on Nox4 expression and oxidative activity. Moreover, MG132 exposed PTCs (L) demostrated blocked ubiquitinated Nox4 degradation and increased colocalization of Nox4/Ubiquitin by inmunofluorescence. Conversely, Hsp72 depletion reduced Nox4/Ubiquitin colocalization causing Nox4 upregulation due to proteosomal degradation inhibition, although Losartan treatment. Conclusion: Our study demonstrates that Hsp70 and CHIP mediates the ubiquitination and proteasomal degradation of Nox4 as part ofthe antioxidative effect of Losartan in SHR.
Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Lopez Appiolaza, Carlos Martìn. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
Fil: Bocanegra, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description Background: Angiotensin II/Angiotensin II type 1 receptor (AT1R) effects are dependent on ROS production stimulated by NADPH oxidase activation. Hsp70 regulates a diverse set of signaling pathways through their interactions with proteins. CHIP is a E3 ubiquitin ligase that targets proteins for polyubiquitination and degradation. Aim: We study whether Hsp70/CHIP contribute to the negative regulation of Nox4 after AT1R blockage. Methods/Results: Primary culture of proximal tubule epithelial cells (PTCs) from SHR and WKY were stimulated with Angiotensin II (AII) or treated with Losartan (L) or Losartan plus Angiotensin II (L+AII). Losartan decreased AT1R and Nox4 while enhancing caveolin-1 and Hsp70 protein expression in SHR PTCs. Immunoprecipitation and immunofluorescence proved interaction and colocalization of increased Hsp70/CHIP with decreased Nox4 in SHR PTCs (L) vs (All). Hsp72 knockdown resulted in enhanced Nox4 protein levels, NADPH oxidase activity and ROS generation in (L+AII) revealing that Losartan was unable to abrogate AII effects on Nox4 expression and oxidative activity. Moreover, MG132 exposed PTCs (L) demostrated blocked ubiquitinated Nox4 degradation and increased colocalization of Nox4/Ubiquitin by inmunofluorescence. Conversely, Hsp72 depletion reduced Nox4/Ubiquitin colocalization causing Nox4 upregulation due to proteosomal degradation inhibition, although Losartan treatment. Conclusion: Our study demonstrates that Hsp70 and CHIP mediates the ubiquitination and proteasomal degradation of Nox4 as part ofthe antioxidative effect of Losartan in SHR.
publishDate 2015
dc.date.none.fl_str_mv 2015-08
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/11336/126805
Costantino, Valeria Victoria; Gil Lorenzo, Andrea Fernanda; Lopez Appiolaza, Carlos Martìn; Cacciamani, Valeria; Benardon, María Eugenia; et al.; Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells; Karger; Cellular Physiology and Biochemistry; 36; 6; 8-2015; 2183-2197
1015-8987
CONICET Digital
CONICET
url http://hdl.handle.net/11336/126805
identifier_str_mv Costantino, Valeria Victoria; Gil Lorenzo, Andrea Fernanda; Lopez Appiolaza, Carlos Martìn; Cacciamani, Valeria; Benardon, María Eugenia; et al.; Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells; Karger; Cellular Physiology and Biochemistry; 36; 6; 8-2015; 2183-2197
1015-8987
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/FullText/430184
info:eu-repo/semantics/altIdentifier/doi/10.1159/000430184
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 Karger
publisher.none.fl_str_mv Karger
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
_version_ 1842268599551524864
score 13.13397

Publicaciones similares