Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway

Autores
de Genaro, Pablo Adrian; Simón, Maria Victoria; Rotstein, Nora Patricia; Politi, Luis Enrique
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose Retinoic acid (RA) has a critical role during development of the retina, controlling cell fate and differentiation. We here investigated RA effects on photoreceptor differentiation and apoptosis and the intracellular pathways involved in these effects. Methods Rat retinal neuronal cultures were supplemented with RA and with or without docosahexaenoic acid (DHA), a photoreceptor trophic factor. Photoreceptor apoptosis and differentiation were evaluated at different times of development. The effect of the pan caspase inhibitor Z-VAD-FMK on apoptosis and differentiation was determined. RA activation of p38 MAP kinase was determined by evaluating phosphorylated (P)-p38 levels in cultures with or without RA and the effect of pre-treatment with SB203580, a p38 specific inhibitor. Results RA addition at day 0, when cells were still proliferating, selectively increased apoptosis in photoreceptors, whereas addition at day 2 no longer caused cell death. DHA and Z-VAD-FMK prevented this early apoptosis. RA stimulated opsin and peripherin expression and neurite outgrowth regardless of time of development. RA addition rapidly increased P-p38 levels, whereas p38 inhibition decreased RA-induced differentiation and apoptosis, without affecting neurite outgrowth. Conclusions Our results show that RA stimulated differentiation and induced an early apoptosis in photoreceptors, which were rescued by DHA addition. Noteworthy, activation of the p38 intracellular pathway was required for RA effects on both differentiation and apoptosis. This suggests that RA induction of differentiation during early development must be counterbalanced by survival factors, such as DHA, to prevent photoreceptor death and this interplay might help to establish the final number of photoreceptors.
Fil: de Genaro, Pablo Adrian. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Simón, Maria Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Materia
PHOTORECEPTORS
RETINOIC ACID
APOPTOSIS
RETINA
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:11336/4521
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4521
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathwayde Genaro, Pablo AdrianSimón, Maria VictoriaRotstein, Nora PatriciaPoliti, Luis EnriquePHOTORECEPTORSRETINOIC ACIDAPOPTOSISRETINAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Purpose Retinoic acid (RA) has a critical role during development of the retina, controlling cell fate and differentiation. We here investigated RA effects on photoreceptor differentiation and apoptosis and the intracellular pathways involved in these effects. Methods Rat retinal neuronal cultures were supplemented with RA and with or without docosahexaenoic acid (DHA), a photoreceptor trophic factor. Photoreceptor apoptosis and differentiation were evaluated at different times of development. The effect of the pan caspase inhibitor Z-VAD-FMK on apoptosis and differentiation was determined. RA activation of p38 MAP kinase was determined by evaluating phosphorylated (P)-p38 levels in cultures with or without RA and the effect of pre-treatment with SB203580, a p38 specific inhibitor. Results RA addition at day 0, when cells were still proliferating, selectively increased apoptosis in photoreceptors, whereas addition at day 2 no longer caused cell death. DHA and Z-VAD-FMK prevented this early apoptosis. RA stimulated opsin and peripherin expression and neurite outgrowth regardless of time of development. RA addition rapidly increased P-p38 levels, whereas p38 inhibition decreased RA-induced differentiation and apoptosis, without affecting neurite outgrowth. Conclusions Our results show that RA stimulated differentiation and induced an early apoptosis in photoreceptors, which were rescued by DHA addition. Noteworthy, activation of the p38 intracellular pathway was required for RA effects on both differentiation and apoptosis. This suggests that RA induction of differentiation during early development must be counterbalanced by survival factors, such as DHA, to prevent photoreceptor death and this interplay might help to establish the final number of photoreceptors.Fil: de Genaro, Pablo Adrian. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Simón, Maria Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaAssociation For Research In Vision And Ophthalmology2013-04info: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/11336/4521de Genaro, Pablo Adrian; Simón, Maria Victoria; Rotstein, Nora Patricia; Politi, Luis Enrique; Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway; Association For Research In Vision And Ophthalmology; Investigative Ophthalmology & Visual Science; 54; 4-2013; 3143-31560146-0404http://dx.doi.org/10.1167/iovs.12-11049enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/ark/http://www.ncbi.nlm.nih.gov/pubmed/23580485info:eu-repo/semantics/altIdentifier/ark/http://iovs.arvojournals.org/article.aspx?articleid=2189053info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:00:38Zoai:ri.conicet.gov.ar:11336/4521instacron: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:34982025-09-10 13:00:38.632CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
title Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
spellingShingle Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
de Genaro, Pablo Adrian
PHOTORECEPTORS
RETINOIC ACID
APOPTOSIS
RETINA
title_short Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
title_full Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
title_fullStr Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
title_full_unstemmed Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
title_sort Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
dc.creator.none.fl_str_mv de Genaro, Pablo Adrian
Simón, Maria Victoria
Rotstein, Nora Patricia
Politi, Luis Enrique
author de Genaro, Pablo Adrian
author_facet de Genaro, Pablo Adrian
Simón, Maria Victoria
Rotstein, Nora Patricia
Politi, Luis Enrique
author_role author
author2 Simón, Maria Victoria
Rotstein, Nora Patricia
Politi, Luis Enrique
author2_role author
author
author
dc.subject.none.fl_str_mv PHOTORECEPTORS
RETINOIC ACID
APOPTOSIS
RETINA
topic PHOTORECEPTORS
RETINOIC ACID
APOPTOSIS
RETINA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Purpose Retinoic acid (RA) has a critical role during development of the retina, controlling cell fate and differentiation. We here investigated RA effects on photoreceptor differentiation and apoptosis and the intracellular pathways involved in these effects. Methods Rat retinal neuronal cultures were supplemented with RA and with or without docosahexaenoic acid (DHA), a photoreceptor trophic factor. Photoreceptor apoptosis and differentiation were evaluated at different times of development. The effect of the pan caspase inhibitor Z-VAD-FMK on apoptosis and differentiation was determined. RA activation of p38 MAP kinase was determined by evaluating phosphorylated (P)-p38 levels in cultures with or without RA and the effect of pre-treatment with SB203580, a p38 specific inhibitor. Results RA addition at day 0, when cells were still proliferating, selectively increased apoptosis in photoreceptors, whereas addition at day 2 no longer caused cell death. DHA and Z-VAD-FMK prevented this early apoptosis. RA stimulated opsin and peripherin expression and neurite outgrowth regardless of time of development. RA addition rapidly increased P-p38 levels, whereas p38 inhibition decreased RA-induced differentiation and apoptosis, without affecting neurite outgrowth. Conclusions Our results show that RA stimulated differentiation and induced an early apoptosis in photoreceptors, which were rescued by DHA addition. Noteworthy, activation of the p38 intracellular pathway was required for RA effects on both differentiation and apoptosis. This suggests that RA induction of differentiation during early development must be counterbalanced by survival factors, such as DHA, to prevent photoreceptor death and this interplay might help to establish the final number of photoreceptors.
Fil: de Genaro, Pablo Adrian. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Simón, Maria Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
description Purpose Retinoic acid (RA) has a critical role during development of the retina, controlling cell fate and differentiation. We here investigated RA effects on photoreceptor differentiation and apoptosis and the intracellular pathways involved in these effects. Methods Rat retinal neuronal cultures were supplemented with RA and with or without docosahexaenoic acid (DHA), a photoreceptor trophic factor. Photoreceptor apoptosis and differentiation were evaluated at different times of development. The effect of the pan caspase inhibitor Z-VAD-FMK on apoptosis and differentiation was determined. RA activation of p38 MAP kinase was determined by evaluating phosphorylated (P)-p38 levels in cultures with or without RA and the effect of pre-treatment with SB203580, a p38 specific inhibitor. Results RA addition at day 0, when cells were still proliferating, selectively increased apoptosis in photoreceptors, whereas addition at day 2 no longer caused cell death. DHA and Z-VAD-FMK prevented this early apoptosis. RA stimulated opsin and peripherin expression and neurite outgrowth regardless of time of development. RA addition rapidly increased P-p38 levels, whereas p38 inhibition decreased RA-induced differentiation and apoptosis, without affecting neurite outgrowth. Conclusions Our results show that RA stimulated differentiation and induced an early apoptosis in photoreceptors, which were rescued by DHA addition. Noteworthy, activation of the p38 intracellular pathway was required for RA effects on both differentiation and apoptosis. This suggests that RA induction of differentiation during early development must be counterbalanced by survival factors, such as DHA, to prevent photoreceptor death and this interplay might help to establish the final number of photoreceptors.
publishDate 2013
dc.date.none.fl_str_mv 2013-04
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/11336/4521
de Genaro, Pablo Adrian; Simón, Maria Victoria; Rotstein, Nora Patricia; Politi, Luis Enrique; Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway; Association For Research In Vision And Ophthalmology; Investigative Ophthalmology & Visual Science; 54; 4-2013; 3143-3156
0146-0404
http://dx.doi.org/10.1167/iovs.12-11049
url http://hdl.handle.net/11336/4521
http://dx.doi.org/10.1167/iovs.12-11049
identifier_str_mv de Genaro, Pablo Adrian; Simón, Maria Victoria; Rotstein, Nora Patricia; Politi, Luis Enrique; Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway; Association For Research In Vision And Ophthalmology; Investigative Ophthalmology & Visual Science; 54; 4-2013; 3143-3156
0146-0404
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/ark/http://www.ncbi.nlm.nih.gov/pubmed/23580485
info:eu-repo/semantics/altIdentifier/ark/http://iovs.arvojournals.org/article.aspx?articleid=2189053
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 Association For Research In Vision And Ophthalmology
publisher.none.fl_str_mv Association For Research In Vision And Ophthalmology
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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score 12.993085

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