Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment

Autores
Ayala Peña, Victoria Belen; German, Olga Lorena
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Age-related macular degeneration (AMD) is the main pathology leading to blindness in adults and has no cure or effective treatment. Retinal pigment epithelial (RPE) cells have immunomodulatory properties and their degeneration contributes in AMD development. Oxidative stress is also involved in the pathogenesis of this disease. We have demonstrated that RXR activation with HX630 protects RPE (D407) cells from H2O2-induced apoptosis, and prevents NFkB nuclear translocation. Also, our previous results suggested RXR- PPARgamma as the main heterodimer involved. In this work we investigate the RXR-PPARgamma involvement in the mentioned protective effect and its mechanism of action. For that, D407 were treated or not with H2O2, HX630 and/or a PPARgamma specific agonist (Pioglitazone: PG). We analyzed cell viability by MTT assay and DAPI stained; and studied NFkB pathway (which modulates inflammation and apoptosis) and Nrf2 (which activates cytoprotective genes and regulates NFkB pathway) by qRT-PCR, florescence microscopy and Western-blot. PG reproduced the inhibition of NFkB translocation and the protective effect of RXR activation against oxidative damage. PG inhibited the IKBalpha phosphorylation more than HX630, while it promoted IKBalpha synthesis. When HX630 and PG were together, the inhibition of NFkB translocation was higher than the agonists alone, although, there was no synergism in apoptosis prevention. HX630 increases Nrf2 synthesis, PG does not, and both agonists together decrease NrF2 levels suggesting proteosomal degradation. As a whole, our results show that RXR and PPARgamma agonists together potentiate the anti- inflammatory response but not the antiapoptotic effects of each agonist alone on RPE cells upon oxidative stress, and suggest that both agonists are necessary together to alter the crosstalk between NrF2 and NFkB pathway.
Fil: Ayala Peña, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: German, Olga Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL)
mar del plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
Materia
RPE CELLS
NFKB PATHWAY
RETINOID X RECEPTOR
NRF2
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:11336/189459
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/189459
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatmentAyala Peña, Victoria BelenGerman, Olga LorenaRPE CELLSNFKB PATHWAYRETINOID X RECEPTORNRF2https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Age-related macular degeneration (AMD) is the main pathology leading to blindness in adults and has no cure or effective treatment. Retinal pigment epithelial (RPE) cells have immunomodulatory properties and their degeneration contributes in AMD development. Oxidative stress is also involved in the pathogenesis of this disease. We have demonstrated that RXR activation with HX630 protects RPE (D407) cells from H2O2-induced apoptosis, and prevents NFkB nuclear translocation. Also, our previous results suggested RXR- PPARgamma as the main heterodimer involved. In this work we investigate the RXR-PPARgamma involvement in the mentioned protective effect and its mechanism of action. For that, D407 were treated or not with H2O2, HX630 and/or a PPARgamma specific agonist (Pioglitazone: PG). We analyzed cell viability by MTT assay and DAPI stained; and studied NFkB pathway (which modulates inflammation and apoptosis) and Nrf2 (which activates cytoprotective genes and regulates NFkB pathway) by qRT-PCR, florescence microscopy and Western-blot. PG reproduced the inhibition of NFkB translocation and the protective effect of RXR activation against oxidative damage. PG inhibited the IKBalpha phosphorylation more than HX630, while it promoted IKBalpha synthesis. When HX630 and PG were together, the inhibition of NFkB translocation was higher than the agonists alone, although, there was no synergism in apoptosis prevention. HX630 increases Nrf2 synthesis, PG does not, and both agonists together decrease NrF2 levels suggesting proteosomal degradation. As a whole, our results show that RXR and PPARgamma agonists together potentiate the anti- inflammatory response but not the antiapoptotic effects of each agonist alone on RPE cells upon oxidative stress, and suggest that both agonists are necessary together to alter the crosstalk between NrF2 and NFkB pathway.Fil: Ayala Peña, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: German, Olga Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaReunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL)mar del plataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical SocietyMedicina (Buenos Aires)Kotsias, Basilio Aristidesde Vito, EduardoNarvaiz Kantor, IsabelSemeniuk, Guillermo Basilio2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/189459Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment; Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL); mar del plata; Argentina; 2019; 210-2100025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:28Zoai:ri.conicet.gov.ar:11336/189459instacron: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 09:39:28.624CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
title Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
spellingShingle Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
Ayala Peña, Victoria Belen
RPE CELLS
NFKB PATHWAY
RETINOID X RECEPTOR
NRF2
title_short Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
title_full Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
title_fullStr Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
title_full_unstemmed Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
title_sort Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment
dc.creator.none.fl_str_mv Ayala Peña, Victoria Belen
German, Olga Lorena
author Ayala Peña, Victoria Belen
author_facet Ayala Peña, Victoria Belen
German, Olga Lorena
author_role author
author2 German, Olga Lorena
author2_role author
dc.contributor.none.fl_str_mv Kotsias, Basilio Aristides
de Vito, Eduardo
Narvaiz Kantor, Isabel
Semeniuk, Guillermo Basilio
dc.subject.none.fl_str_mv RPE CELLS
NFKB PATHWAY
RETINOID X RECEPTOR
NRF2
topic RPE CELLS
NFKB PATHWAY
RETINOID X RECEPTOR
NRF2
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Age-related macular degeneration (AMD) is the main pathology leading to blindness in adults and has no cure or effective treatment. Retinal pigment epithelial (RPE) cells have immunomodulatory properties and their degeneration contributes in AMD development. Oxidative stress is also involved in the pathogenesis of this disease. We have demonstrated that RXR activation with HX630 protects RPE (D407) cells from H2O2-induced apoptosis, and prevents NFkB nuclear translocation. Also, our previous results suggested RXR- PPARgamma as the main heterodimer involved. In this work we investigate the RXR-PPARgamma involvement in the mentioned protective effect and its mechanism of action. For that, D407 were treated or not with H2O2, HX630 and/or a PPARgamma specific agonist (Pioglitazone: PG). We analyzed cell viability by MTT assay and DAPI stained; and studied NFkB pathway (which modulates inflammation and apoptosis) and Nrf2 (which activates cytoprotective genes and regulates NFkB pathway) by qRT-PCR, florescence microscopy and Western-blot. PG reproduced the inhibition of NFkB translocation and the protective effect of RXR activation against oxidative damage. PG inhibited the IKBalpha phosphorylation more than HX630, while it promoted IKBalpha synthesis. When HX630 and PG were together, the inhibition of NFkB translocation was higher than the agonists alone, although, there was no synergism in apoptosis prevention. HX630 increases Nrf2 synthesis, PG does not, and both agonists together decrease NrF2 levels suggesting proteosomal degradation. As a whole, our results show that RXR and PPARgamma agonists together potentiate the anti- inflammatory response but not the antiapoptotic effects of each agonist alone on RPE cells upon oxidative stress, and suggest that both agonists are necessary together to alter the crosstalk between NrF2 and NFkB pathway.
Fil: Ayala Peña, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: German, Olga Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL)
mar del plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
description Age-related macular degeneration (AMD) is the main pathology leading to blindness in adults and has no cure or effective treatment. Retinal pigment epithelial (RPE) cells have immunomodulatory properties and their degeneration contributes in AMD development. Oxidative stress is also involved in the pathogenesis of this disease. We have demonstrated that RXR activation with HX630 protects RPE (D407) cells from H2O2-induced apoptosis, and prevents NFkB nuclear translocation. Also, our previous results suggested RXR- PPARgamma as the main heterodimer involved. In this work we investigate the RXR-PPARgamma involvement in the mentioned protective effect and its mechanism of action. For that, D407 were treated or not with H2O2, HX630 and/or a PPARgamma specific agonist (Pioglitazone: PG). We analyzed cell viability by MTT assay and DAPI stained; and studied NFkB pathway (which modulates inflammation and apoptosis) and Nrf2 (which activates cytoprotective genes and regulates NFkB pathway) by qRT-PCR, florescence microscopy and Western-blot. PG reproduced the inhibition of NFkB translocation and the protective effect of RXR activation against oxidative damage. PG inhibited the IKBalpha phosphorylation more than HX630, while it promoted IKBalpha synthesis. When HX630 and PG were together, the inhibition of NFkB translocation was higher than the agonists alone, although, there was no synergism in apoptosis prevention. HX630 increases Nrf2 synthesis, PG does not, and both agonists together decrease NrF2 levels suggesting proteosomal degradation. As a whole, our results show that RXR and PPARgamma agonists together potentiate the anti- inflammatory response but not the antiapoptotic effects of each agonist alone on RPE cells upon oxidative stress, and suggest that both agonists are necessary together to alter the crosstalk between NrF2 and NFkB pathway.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/189459
Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment; Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL); mar del plata; Argentina; 2019; 210-210
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/189459
identifier_str_mv Retinoid X Receptor´s activation modulates a crosstalk between NrF2 and NFkB pathway in retinal pigment epithelium cells upon H2O2 treatment; Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL); mar del plata; Argentina; 2019; 210-210
0025-7680
1669-9106
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.saic.org.ar/revista-medicina
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
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application/pdf
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Medicina (Buenos Aires)
publisher.none.fl_str_mv Medicina (Buenos Aires)
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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