Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors

Autores
Miranda, Gisela Edit; Abrahan, Carolina Elizabeth; Politi, Luis Enrique; Rotstein, Nora Patricia
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
PURPOSE. Identifying the cues required for survival and development of photoreceptors is essential for treating retina neurodegenerations. We previously established that glial derived neurotrophic factor (GDNF) stimulates proliferation and that docosahexaenoic acid (DHA) promotes photoreceptor survival and differentiation. Our later finding that ceramide triggers photoreceptor apoptosis suggested sphingolipids might also control photoreceptor development. We now investigated whether sphingosine-1-phophate (S1P), which promotes survival and differentiation in several cell types, regulates photoreceptor proliferation and differentiation and whether it is a mediator in GDNF and DHA effects. METHODS. Rat retina neuronal cultures were supplemented at day 0 or 1 with S1P, GDNF or DHA and treated with DL-threo-dihydrosphingosine (DHS) to inhibit S1P synthesis or with Brefeldin A (BFA) to block intracellular trafficking. Proliferation was quantified determining bromodeoxyuridine uptake and number of mitotic figures. Opsin, peripherin and sphingosine kinase (SphK), the enzyme required for S1P synthesis, were quantified by immunocytochemistry and Western blot. RESULTS. S1P increased proliferation of photoreceptor progenitors. It also stimulated formation of apical processes, enhanced opsin and peripherin expression and promoted their localization in these processes; DHA had similar effects. BFA prevented S1P and DHA enhancement of apical process formation, without affecting opsin expression. While GDNF and DHA enhanced SphK expression in photoreceptors, inhibiting S1P synthesis blocked GDNF mitogenic effect and DHA effects on differentiation. CONCLUSIONS. We propose S1P as a key regulator in photoreceptor development. GDNF and DHA might upregulate SphK levels to promote S1P synthesis, which would initially promote proliferation and then advance photoreceptor differentiation.
Fil: Miranda, Gisela Edit. 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
Fil: Abrahan, Carolina Elizabeth. 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
Fil: Politi, Luis Enrique. 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
Fil: Rotstein, Nora Patricia. 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
Materia
Sphingosine-1-Phosphate
Proliferation
Differentiation
Photoreceptors
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:11336/45728
Acceder
id CONICETDig_791f83dff50826d7b805f6c6274aa6f2
oai_identifier_str oai:ri.conicet.gov.ar:11336/45728
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina PhotoreceptorsMiranda, Gisela EditAbrahan, Carolina ElizabethPoliti, Luis EnriqueRotstein, Nora PatriciaSphingosine-1-PhosphateProliferationDifferentiationPhotoreceptorshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1PURPOSE. Identifying the cues required for survival and development of photoreceptors is essential for treating retina neurodegenerations. We previously established that glial derived neurotrophic factor (GDNF) stimulates proliferation and that docosahexaenoic acid (DHA) promotes photoreceptor survival and differentiation. Our later finding that ceramide triggers photoreceptor apoptosis suggested sphingolipids might also control photoreceptor development. We now investigated whether sphingosine-1-phophate (S1P), which promotes survival and differentiation in several cell types, regulates photoreceptor proliferation and differentiation and whether it is a mediator in GDNF and DHA effects. METHODS. Rat retina neuronal cultures were supplemented at day 0 or 1 with S1P, GDNF or DHA and treated with DL-threo-dihydrosphingosine (DHS) to inhibit S1P synthesis or with Brefeldin A (BFA) to block intracellular trafficking. Proliferation was quantified determining bromodeoxyuridine uptake and number of mitotic figures. Opsin, peripherin and sphingosine kinase (SphK), the enzyme required for S1P synthesis, were quantified by immunocytochemistry and Western blot. RESULTS. S1P increased proliferation of photoreceptor progenitors. It also stimulated formation of apical processes, enhanced opsin and peripherin expression and promoted their localization in these processes; DHA had similar effects. BFA prevented S1P and DHA enhancement of apical process formation, without affecting opsin expression. While GDNF and DHA enhanced SphK expression in photoreceptors, inhibiting S1P synthesis blocked GDNF mitogenic effect and DHA effects on differentiation. CONCLUSIONS. We propose S1P as a key regulator in photoreceptor development. GDNF and DHA might upregulate SphK levels to promote S1P synthesis, which would initially promote proliferation and then advance photoreceptor differentiation.Fil: Miranda, Gisela Edit. 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; ArgentinaFil: Abrahan, Carolina Elizabeth. 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; ArgentinaFil: Politi, Luis Enrique. 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; ArgentinaFil: Rotstein, Nora Patricia. 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; ArgentinaAssociation for Research in Vision and Ophthalmology2009-09info: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/11336/45728Miranda, Gisela Edit; Abrahan, Carolina Elizabeth; Politi, Luis Enrique; Rotstein, Nora Patricia; Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors; Association for Research in Vision and Ophthalmology; Investigative Opthalmology & Visual Science; 50; 9; 9-2009; 4416-44281552-5783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.09-3388info:eu-repo/semantics/altIdentifier/url/http://iovs.arvojournals.org/article.aspx?articleid=2186010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:46:41Zoai:ri.conicet.gov.ar:11336/45728instacron: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:34982025-10-22 11:46:41.856CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
title Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
spellingShingle Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
Miranda, Gisela Edit
Sphingosine-1-Phosphate
Proliferation
Differentiation
Photoreceptors
title_short Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
title_full Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
title_fullStr Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
title_full_unstemmed Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
title_sort Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors
dc.creator.none.fl_str_mv Miranda, Gisela Edit
Abrahan, Carolina Elizabeth
Politi, Luis Enrique
Rotstein, Nora Patricia
author Miranda, Gisela Edit
author_facet Miranda, Gisela Edit
Abrahan, Carolina Elizabeth
Politi, Luis Enrique
Rotstein, Nora Patricia
author_role author
author2 Abrahan, Carolina Elizabeth
Politi, Luis Enrique
Rotstein, Nora Patricia
author2_role author
author
author
dc.subject.none.fl_str_mv Sphingosine-1-Phosphate
Proliferation
Differentiation
Photoreceptors
topic Sphingosine-1-Phosphate
Proliferation
Differentiation
Photoreceptors
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. Identifying the cues required for survival and development of photoreceptors is essential for treating retina neurodegenerations. We previously established that glial derived neurotrophic factor (GDNF) stimulates proliferation and that docosahexaenoic acid (DHA) promotes photoreceptor survival and differentiation. Our later finding that ceramide triggers photoreceptor apoptosis suggested sphingolipids might also control photoreceptor development. We now investigated whether sphingosine-1-phophate (S1P), which promotes survival and differentiation in several cell types, regulates photoreceptor proliferation and differentiation and whether it is a mediator in GDNF and DHA effects. METHODS. Rat retina neuronal cultures were supplemented at day 0 or 1 with S1P, GDNF or DHA and treated with DL-threo-dihydrosphingosine (DHS) to inhibit S1P synthesis or with Brefeldin A (BFA) to block intracellular trafficking. Proliferation was quantified determining bromodeoxyuridine uptake and number of mitotic figures. Opsin, peripherin and sphingosine kinase (SphK), the enzyme required for S1P synthesis, were quantified by immunocytochemistry and Western blot. RESULTS. S1P increased proliferation of photoreceptor progenitors. It also stimulated formation of apical processes, enhanced opsin and peripherin expression and promoted their localization in these processes; DHA had similar effects. BFA prevented S1P and DHA enhancement of apical process formation, without affecting opsin expression. While GDNF and DHA enhanced SphK expression in photoreceptors, inhibiting S1P synthesis blocked GDNF mitogenic effect and DHA effects on differentiation. CONCLUSIONS. We propose S1P as a key regulator in photoreceptor development. GDNF and DHA might upregulate SphK levels to promote S1P synthesis, which would initially promote proliferation and then advance photoreceptor differentiation.
Fil: Miranda, Gisela Edit. 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
Fil: Abrahan, Carolina Elizabeth. 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
Fil: Politi, Luis Enrique. 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
Fil: Rotstein, Nora Patricia. 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
description PURPOSE. Identifying the cues required for survival and development of photoreceptors is essential for treating retina neurodegenerations. We previously established that glial derived neurotrophic factor (GDNF) stimulates proliferation and that docosahexaenoic acid (DHA) promotes photoreceptor survival and differentiation. Our later finding that ceramide triggers photoreceptor apoptosis suggested sphingolipids might also control photoreceptor development. We now investigated whether sphingosine-1-phophate (S1P), which promotes survival and differentiation in several cell types, regulates photoreceptor proliferation and differentiation and whether it is a mediator in GDNF and DHA effects. METHODS. Rat retina neuronal cultures were supplemented at day 0 or 1 with S1P, GDNF or DHA and treated with DL-threo-dihydrosphingosine (DHS) to inhibit S1P synthesis or with Brefeldin A (BFA) to block intracellular trafficking. Proliferation was quantified determining bromodeoxyuridine uptake and number of mitotic figures. Opsin, peripherin and sphingosine kinase (SphK), the enzyme required for S1P synthesis, were quantified by immunocytochemistry and Western blot. RESULTS. S1P increased proliferation of photoreceptor progenitors. It also stimulated formation of apical processes, enhanced opsin and peripherin expression and promoted their localization in these processes; DHA had similar effects. BFA prevented S1P and DHA enhancement of apical process formation, without affecting opsin expression. While GDNF and DHA enhanced SphK expression in photoreceptors, inhibiting S1P synthesis blocked GDNF mitogenic effect and DHA effects on differentiation. CONCLUSIONS. We propose S1P as a key regulator in photoreceptor development. GDNF and DHA might upregulate SphK levels to promote S1P synthesis, which would initially promote proliferation and then advance photoreceptor differentiation.
publishDate 2009
dc.date.none.fl_str_mv 2009-09
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/11336/45728
Miranda, Gisela Edit; Abrahan, Carolina Elizabeth; Politi, Luis Enrique; Rotstein, Nora Patricia; Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors; Association for Research in Vision and Ophthalmology; Investigative Opthalmology & Visual Science; 50; 9; 9-2009; 4416-4428
1552-5783
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45728
identifier_str_mv Miranda, Gisela Edit; Abrahan, Carolina Elizabeth; Politi, Luis Enrique; Rotstein, Nora Patricia; Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors; Association for Research in Vision and Ophthalmology; Investigative Opthalmology & Visual Science; 50; 9; 9-2009; 4416-4428
1552-5783
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.09-3388
info:eu-repo/semantics/altIdentifier/url/http://iovs.arvojournals.org/article.aspx?articleid=2186010
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 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
_version_ 1846782169535479808
score 12.928904

Publicaciones similares