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dc.contributor.author
Costantino, Valeria Victoria
dc.contributor.author
Gil Lorenzo, Andrea Fernanda
dc.contributor.author
Lopez Appiolaza, Carlos Martìn
dc.contributor.author
Cacciamani, Valeria
dc.contributor.author
Benardon, María Eugenia
dc.contributor.author
Bocanegra, María Victoria
dc.contributor.author
Garramuño, Patricia
dc.date.available
2021-02-26T16:57:50Z
dc.date.issued
2015-08
dc.identifier.citation
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
dc.identifier.issn
1015-8987
dc.identifier.uri
http://hdl.handle.net/11336/126805
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Karger
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ANGIOTENSIN II
dc.subject
LOSARTAN
dc.subject
NOX4/HSP70/CHIP
dc.subject
PROXIMAL TUBULE CELLS
dc.subject
UBIQUITINATION
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-12-04T18:39:16Z
dc.journal.volume
36
dc.journal.number
6
dc.journal.pagination
2183-2197
dc.journal.pais
Suiza
dc.journal.ciudad
Basilea
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
Fil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
dc.description.fil
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
dc.description.fil
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
dc.journal.title
Cellular Physiology and Biochemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/FullText/430184
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1159/000430184
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