Ceramide induces the death of retina photoreceptors through activation of parthanatos

Autores
Prado Spalm, Facundo Heber; Vera, Marcela Sonia; Dibo, Marcos Javier; Simon, Maria Victoria; Politi, Luis Enrique; Rotstein, Nora Patricia
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Ceramide (Cer) has been proposed as a messenger in photoreceptor cell death in the retina. Here we explored the pathways induced by C2-acetylsphingosine (C2-Cer), a cell permeable Cer, to elicit photoreceptor death. Treating pure retina neuronal cultures with 10 µM C2-Cer for 6 h selectively induced photoreceptor death, decreasing mitochondrial membrane potential and increasing the formation of reactive oxygen species. Noteworthy, the amount of TUNEL-labeled cells and photoreceptors expressing cleaved-caspase 3 remained constant and pretreatment with a pan caspase inhibitor did not prevent C2-Cer-induced death. C2-Cer provoked polyADP ribosyl polymerase-1 (PARP-1) overactivation. increased polyADP ribose polymer (PAR) levels and induced the nuclear translocation of apoptosis inducing factor (AIF). Inhibiting PARP-1 decreased C2-Cer induced photoreceptor death and prevented AIF translocation. A calpain inhibitor reduced photoreceptor death whereas selective cathepsin inhibitors granted no protection. Combined pretreatment with a PARP-1 and a calpain inhibitor evidenced the same protection as each inhibitor by itself. Neither autophagy nor necroptosis were involved in C2-Cer-elicited death. These results suggest that C2-Cer induced photoreceptor death by a novel, caspase independent mechanism, involving activation of PARP-1, decline of mitochondrial membrane potential, calpain activation and AIF translocation, which are all biochemical features of parthanatos.
Fil: Prado Spalm, Facundo Heber. 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: Vera, Marcela Sonia. 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: Dibo, Marcos Javier. 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: Simon, Maria Victoria. 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: 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXIII Annual Congress of the Argentine Society of Neuroscience Research
Córdoba
Argentina
Sociedad Argenina de Investigacion en Neurociencias
Materia
CERAMIDE
AIF
CALPAIN
PHOTORECEPTOR DEATH
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:11336/174094
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/174094
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ceramide induces the death of retina photoreceptors through activation of parthanatosPrado Spalm, Facundo HeberVera, Marcela SoniaDibo, Marcos JavierSimon, Maria VictoriaPoliti, Luis EnriqueRotstein, Nora PatriciaCERAMIDEAIFCALPAINPHOTORECEPTOR DEATHhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Ceramide (Cer) has been proposed as a messenger in photoreceptor cell death in the retina. Here we explored the pathways induced by C2-acetylsphingosine (C2-Cer), a cell permeable Cer, to elicit photoreceptor death. Treating pure retina neuronal cultures with 10 µM C2-Cer for 6 h selectively induced photoreceptor death, decreasing mitochondrial membrane potential and increasing the formation of reactive oxygen species. Noteworthy, the amount of TUNEL-labeled cells and photoreceptors expressing cleaved-caspase 3 remained constant and pretreatment with a pan caspase inhibitor did not prevent C2-Cer-induced death. C2-Cer provoked polyADP ribosyl polymerase-1 (PARP-1) overactivation. increased polyADP ribose polymer (PAR) levels and induced the nuclear translocation of apoptosis inducing factor (AIF). Inhibiting PARP-1 decreased C2-Cer induced photoreceptor death and prevented AIF translocation. A calpain inhibitor reduced photoreceptor death whereas selective cathepsin inhibitors granted no protection. Combined pretreatment with a PARP-1 and a calpain inhibitor evidenced the same protection as each inhibitor by itself. Neither autophagy nor necroptosis were involved in C2-Cer-elicited death. These results suggest that C2-Cer induced photoreceptor death by a novel, caspase independent mechanism, involving activation of PARP-1, decline of mitochondrial membrane potential, calpain activation and AIF translocation, which are all biochemical features of parthanatos.Fil: Prado Spalm, Facundo Heber. 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: Vera, Marcela Sonia. 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: Dibo, Marcos Javier. 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: Simon, Maria Victoria. 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: 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaXXXIII Annual Congress of the Argentine Society of Neuroscience ResearchCórdobaArgentinaSociedad Argenina de Investigacion en NeurocienciasSociedad Argenina de Investigacion en Neurociencias2018info: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/11336/174094Ceramide induces the death of retina photoreceptors through activation of parthanatos; XXXIII Annual Congress of the Argentine Society of Neuroscience Research; Córdoba; Argentina; 2018; 175-175CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/info:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:27:01Zoai:ri.conicet.gov.ar:11336/174094instacron: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 11:27:01.464CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ceramide induces the death of retina photoreceptors through activation of parthanatos
title Ceramide induces the death of retina photoreceptors through activation of parthanatos
spellingShingle Ceramide induces the death of retina photoreceptors through activation of parthanatos
Prado Spalm, Facundo Heber
CERAMIDE
AIF
CALPAIN
PHOTORECEPTOR DEATH
title_short Ceramide induces the death of retina photoreceptors through activation of parthanatos
title_full Ceramide induces the death of retina photoreceptors through activation of parthanatos
title_fullStr Ceramide induces the death of retina photoreceptors through activation of parthanatos
title_full_unstemmed Ceramide induces the death of retina photoreceptors through activation of parthanatos
title_sort Ceramide induces the death of retina photoreceptors through activation of parthanatos
dc.creator.none.fl_str_mv Prado Spalm, Facundo Heber
Vera, Marcela Sonia
Dibo, Marcos Javier
Simon, Maria Victoria
Politi, Luis Enrique
Rotstein, Nora Patricia
author Prado Spalm, Facundo Heber
author_facet Prado Spalm, Facundo Heber
Vera, Marcela Sonia
Dibo, Marcos Javier
Simon, Maria Victoria
Politi, Luis Enrique
Rotstein, Nora Patricia
author_role author
author2 Vera, Marcela Sonia
Dibo, Marcos Javier
Simon, Maria Victoria
Politi, Luis Enrique
Rotstein, Nora Patricia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CERAMIDE
AIF
CALPAIN
PHOTORECEPTOR DEATH
topic CERAMIDE
AIF
CALPAIN
PHOTORECEPTOR DEATH
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Ceramide (Cer) has been proposed as a messenger in photoreceptor cell death in the retina. Here we explored the pathways induced by C2-acetylsphingosine (C2-Cer), a cell permeable Cer, to elicit photoreceptor death. Treating pure retina neuronal cultures with 10 µM C2-Cer for 6 h selectively induced photoreceptor death, decreasing mitochondrial membrane potential and increasing the formation of reactive oxygen species. Noteworthy, the amount of TUNEL-labeled cells and photoreceptors expressing cleaved-caspase 3 remained constant and pretreatment with a pan caspase inhibitor did not prevent C2-Cer-induced death. C2-Cer provoked polyADP ribosyl polymerase-1 (PARP-1) overactivation. increased polyADP ribose polymer (PAR) levels and induced the nuclear translocation of apoptosis inducing factor (AIF). Inhibiting PARP-1 decreased C2-Cer induced photoreceptor death and prevented AIF translocation. A calpain inhibitor reduced photoreceptor death whereas selective cathepsin inhibitors granted no protection. Combined pretreatment with a PARP-1 and a calpain inhibitor evidenced the same protection as each inhibitor by itself. Neither autophagy nor necroptosis were involved in C2-Cer-elicited death. These results suggest that C2-Cer induced photoreceptor death by a novel, caspase independent mechanism, involving activation of PARP-1, decline of mitochondrial membrane potential, calpain activation and AIF translocation, which are all biochemical features of parthanatos.
Fil: Prado Spalm, Facundo Heber. 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: Vera, Marcela Sonia. 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: Dibo, Marcos Javier. 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: Simon, Maria Victoria. 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: 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXIII Annual Congress of the Argentine Society of Neuroscience Research
Córdoba
Argentina
Sociedad Argenina de Investigacion en Neurociencias
description Ceramide (Cer) has been proposed as a messenger in photoreceptor cell death in the retina. Here we explored the pathways induced by C2-acetylsphingosine (C2-Cer), a cell permeable Cer, to elicit photoreceptor death. Treating pure retina neuronal cultures with 10 µM C2-Cer for 6 h selectively induced photoreceptor death, decreasing mitochondrial membrane potential and increasing the formation of reactive oxygen species. Noteworthy, the amount of TUNEL-labeled cells and photoreceptors expressing cleaved-caspase 3 remained constant and pretreatment with a pan caspase inhibitor did not prevent C2-Cer-induced death. C2-Cer provoked polyADP ribosyl polymerase-1 (PARP-1) overactivation. increased polyADP ribose polymer (PAR) levels and induced the nuclear translocation of apoptosis inducing factor (AIF). Inhibiting PARP-1 decreased C2-Cer induced photoreceptor death and prevented AIF translocation. A calpain inhibitor reduced photoreceptor death whereas selective cathepsin inhibitors granted no protection. Combined pretreatment with a PARP-1 and a calpain inhibitor evidenced the same protection as each inhibitor by itself. Neither autophagy nor necroptosis were involved in C2-Cer-elicited death. These results suggest that C2-Cer induced photoreceptor death by a novel, caspase independent mechanism, involving activation of PARP-1, decline of mitochondrial membrane potential, calpain activation and AIF translocation, which are all biochemical features of parthanatos.
publishDate 2018
dc.date.none.fl_str_mv 2018
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/11336/174094
Ceramide induces the death of retina photoreceptors through activation of parthanatos; XXXIII Annual Congress of the Argentine Society of Neuroscience Research; Córdoba; Argentina; 2018; 175-175
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174094
identifier_str_mv Ceramide induces the death of retina photoreceptors through activation of parthanatos; XXXIII Annual Congress of the Argentine Society of Neuroscience Research; Córdoba; Argentina; 2018; 175-175
CONICET Digital
CONICET
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language eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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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
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argenina de Investigacion en Neurociencias
publisher.none.fl_str_mv Sociedad Argenina de Investigacion en Neurociencias
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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