Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors

Autores
German, Olga Lorena; Monaco, Sandra Tanya; Agnolazza, Daniela Luciana; Politi, Luis Enrique; Rotstein, Nora Patricia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have established that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, promotes survival of rat retina photoreceptors during early development in vitro and upon oxidative stress by activating the ERK/MAPK signaling pathway. We now investigated whether DHA turns on this pathway through activation of retinoid X receptors (RXR) or by inducing tyrosine kinase (Trk) receptor activation. We also evaluated whether DHA release from phospholipids was required for its protective effect. Addition of RXR antagonists (HX531, PA452) to rat retinal neuronal cultures inhibited DHA protection during early development in vitro and upon oxidative stress induced with paraquat or H2O2. In contrast, the Trk inhibitor K252a did not affect DHA prevention of photoreceptor apoptosis. These results imply that activation of RXR was required for DHA protection whereas Trk receptors were not involved in this protection. Pretreatment with BEL, a phospholipase A2 inhibitor, blocked DHA prevention of oxidative stress-induced apoptosis of photoreceptors. Noteworthy, RXR agonists (HX630, PA024) also rescued photoreceptors from H2O2-induced apoptosis. These results suggest that DHA is first released from phospholipids and then activates RXR to prevent photoreceptor apoptosis. This is the first evidence in which RXR activation can promote the survival of photoreceptors.
Fil: German, Olga Lorena. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Monaco, Sandra Tanya. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Agnolazza, Daniela Luciana. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Politi, Luis Enrique. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Rotstein, Nora Patricia. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Materia
Photoreceptors
Rxr Agonists
Docosahexaenoic Acid
Apoptosis
Oxidative Damage
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:11336/4522

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oai_identifier_str oai:ri.conicet.gov.ar:11336/4522
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina PhotoreceptorsGerman, Olga LorenaMonaco, Sandra TanyaAgnolazza, Daniela LucianaPoliti, Luis EnriqueRotstein, Nora PatriciaPhotoreceptorsRxr AgonistsDocosahexaenoic AcidApoptosisOxidative Damagehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We have established that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, promotes survival of rat retina photoreceptors during early development in vitro and upon oxidative stress by activating the ERK/MAPK signaling pathway. We now investigated whether DHA turns on this pathway through activation of retinoid X receptors (RXR) or by inducing tyrosine kinase (Trk) receptor activation. We also evaluated whether DHA release from phospholipids was required for its protective effect. Addition of RXR antagonists (HX531, PA452) to rat retinal neuronal cultures inhibited DHA protection during early development in vitro and upon oxidative stress induced with paraquat or H2O2. In contrast, the Trk inhibitor K252a did not affect DHA prevention of photoreceptor apoptosis. These results imply that activation of RXR was required for DHA protection whereas Trk receptors were not involved in this protection. Pretreatment with BEL, a phospholipase A2 inhibitor, blocked DHA prevention of oxidative stress-induced apoptosis of photoreceptors. Noteworthy, RXR agonists (HX630, PA024) also rescued photoreceptors from H2O2-induced apoptosis. These results suggest that DHA is first released from phospholipids and then activates RXR to prevent photoreceptor apoptosis. This is the first evidence in which RXR activation can promote the survival of photoreceptors.Fil: German, Olga Lorena. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Monaco, Sandra Tanya. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Agnolazza, Daniela Luciana. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Politi, Luis Enrique. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Rotstein, Nora Patricia. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaAmerican Society For Biochemistry And Molecular Biology2013-05info: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/pdfhttp://hdl.handle.net/11336/4522German, Olga Lorena; Monaco, Sandra Tanya; Agnolazza, Daniela Luciana; Politi, Luis Enrique; Rotstein, Nora Patricia; Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors; American Society For Biochemistry And Molecular Biology; Jlr Papers In Press; 54; 5-2013; 2236-22460022-22751539-7262enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M039040info:eu-repo/semantics/altIdentifier/url/http://www.jlr.orginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:42:51Zoai:ri.conicet.gov.ar:11336/4522instacron: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:34982025-10-15 15:42:52.028CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
title Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
spellingShingle Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
German, Olga Lorena
Photoreceptors
Rxr Agonists
Docosahexaenoic Acid
Apoptosis
Oxidative Damage
title_short Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
title_full Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
title_fullStr Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
title_full_unstemmed Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
title_sort Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors
dc.creator.none.fl_str_mv German, Olga Lorena
Monaco, Sandra Tanya
Agnolazza, Daniela Luciana
Politi, Luis Enrique
Rotstein, Nora Patricia
author German, Olga Lorena
author_facet German, Olga Lorena
Monaco, Sandra Tanya
Agnolazza, Daniela Luciana
Politi, Luis Enrique
Rotstein, Nora Patricia
author_role author
author2 Monaco, Sandra Tanya
Agnolazza, Daniela Luciana
Politi, Luis Enrique
Rotstein, Nora Patricia
author2_role author
author
author
author
dc.subject.none.fl_str_mv Photoreceptors
Rxr Agonists
Docosahexaenoic Acid
Apoptosis
Oxidative Damage
topic Photoreceptors
Rxr Agonists
Docosahexaenoic Acid
Apoptosis
Oxidative Damage
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We have established that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, promotes survival of rat retina photoreceptors during early development in vitro and upon oxidative stress by activating the ERK/MAPK signaling pathway. We now investigated whether DHA turns on this pathway through activation of retinoid X receptors (RXR) or by inducing tyrosine kinase (Trk) receptor activation. We also evaluated whether DHA release from phospholipids was required for its protective effect. Addition of RXR antagonists (HX531, PA452) to rat retinal neuronal cultures inhibited DHA protection during early development in vitro and upon oxidative stress induced with paraquat or H2O2. In contrast, the Trk inhibitor K252a did not affect DHA prevention of photoreceptor apoptosis. These results imply that activation of RXR was required for DHA protection whereas Trk receptors were not involved in this protection. Pretreatment with BEL, a phospholipase A2 inhibitor, blocked DHA prevention of oxidative stress-induced apoptosis of photoreceptors. Noteworthy, RXR agonists (HX630, PA024) also rescued photoreceptors from H2O2-induced apoptosis. These results suggest that DHA is first released from phospholipids and then activates RXR to prevent photoreceptor apoptosis. This is the first evidence in which RXR activation can promote the survival of photoreceptors.
Fil: German, Olga Lorena. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Monaco, Sandra Tanya. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Agnolazza, Daniela Luciana. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Politi, Luis Enrique. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Rotstein, Nora Patricia. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
description We have established that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, promotes survival of rat retina photoreceptors during early development in vitro and upon oxidative stress by activating the ERK/MAPK signaling pathway. We now investigated whether DHA turns on this pathway through activation of retinoid X receptors (RXR) or by inducing tyrosine kinase (Trk) receptor activation. We also evaluated whether DHA release from phospholipids was required for its protective effect. Addition of RXR antagonists (HX531, PA452) to rat retinal neuronal cultures inhibited DHA protection during early development in vitro and upon oxidative stress induced with paraquat or H2O2. In contrast, the Trk inhibitor K252a did not affect DHA prevention of photoreceptor apoptosis. These results imply that activation of RXR was required for DHA protection whereas Trk receptors were not involved in this protection. Pretreatment with BEL, a phospholipase A2 inhibitor, blocked DHA prevention of oxidative stress-induced apoptosis of photoreceptors. Noteworthy, RXR agonists (HX630, PA024) also rescued photoreceptors from H2O2-induced apoptosis. These results suggest that DHA is first released from phospholipids and then activates RXR to prevent photoreceptor apoptosis. This is the first evidence in which RXR activation can promote the survival of photoreceptors.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
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/11336/4522
German, Olga Lorena; Monaco, Sandra Tanya; Agnolazza, Daniela Luciana; Politi, Luis Enrique; Rotstein, Nora Patricia; Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors; American Society For Biochemistry And Molecular Biology; Jlr Papers In Press; 54; 5-2013; 2236-2246
0022-2275
1539-7262
url http://hdl.handle.net/11336/4522
identifier_str_mv German, Olga Lorena; Monaco, Sandra Tanya; Agnolazza, Daniela Luciana; Politi, Luis Enrique; Rotstein, Nora Patricia; Retinoid X Receptors Activation is Essential for Docosahexanoic Acid Protection of Retina Photoreceptors; American Society For Biochemistry And Molecular Biology; Jlr Papers In Press; 54; 5-2013; 2236-2246
0022-2275
1539-7262
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M039040
info:eu-repo/semantics/altIdentifier/url/http://www.jlr.org
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
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
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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