Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminer...

Autores
de Erausquin, Gabriel Alejandro; Hyrc, Krzyztof; Dorsey, David A.; Mamah, Daniel; Dokucu, Mehmet; Masco, Daniel Hugo; Walton, Timothy; Dikranian, Krikor; Soriano, Mario; Garcia Verdugo, José Manuel; Goldberg, Mark P.; Dugan, Laura L.
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We describe a new molecular mechanism of cell death by excitotoxicity mediated through nuclear transcription factor κB (NFκB) in rat embryonic cultures of dopaminergic neurons. Treatment of mesencephalic cultures with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca2+ monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of NFκB, and transcriptional activation of the oncogenep53. Interruption of any of these steps by specific antagonists prevented neurite pruning and programmed cell death. In contrast, cell death was not prevented by caspase antagonists and only partly prevented by nitric-oxide synthase inhibitors. This signal transduction pathway might be a contributing mechanism in ongoing neuronal death in Parkinson disease.
Fil: de Erausquin, Gabriel Alejandro. Washington University School of Medicine; Estados Unidos
Fil: Hyrc, Krzyztof. Washington University School of Medicine; Estados Unidos
Fil: Dorsey, David A.. Washington University School of Medicine; Estados Unidos
Fil: Mamah, Daniel. Washington University School of Medicine; Estados Unidos
Fil: Dokucu, Mehmet. Washington University School of Medicine; Estados Unidos
Fil: Masco, Daniel Hugo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Walton, Timothy. Washington University School of Medicine; Estados Unidos
Fil: Dikranian, Krikor. Washington University School of Medicine; Estados Unidos
Fil: Soriano, Mario. Universidad de Valencia; España
Fil: Garcia Verdugo, José Manuel. Universidad de Valencia; España
Fil: Goldberg, Mark P.. Washington University School of Medicine; Estados Unidos
Fil: Dugan, Laura L.. Washington University School of Medicine; Estados Unidos
Materia
Parkinson Disease
Nuclear Transcription
Cell 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:11336/67178
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/67178
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neuronsde Erausquin, Gabriel AlejandroHyrc, KrzyztofDorsey, David A.Mamah, DanielDokucu, MehmetMasco, Daniel HugoWalton, TimothyDikranian, KrikorSoriano, MarioGarcia Verdugo, José ManuelGoldberg, Mark P.Dugan, Laura L.Parkinson DiseaseNuclear TranscriptionCell Deathhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We describe a new molecular mechanism of cell death by excitotoxicity mediated through nuclear transcription factor κB (NFκB) in rat embryonic cultures of dopaminergic neurons. Treatment of mesencephalic cultures with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca2+ monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of NFκB, and transcriptional activation of the oncogenep53. Interruption of any of these steps by specific antagonists prevented neurite pruning and programmed cell death. In contrast, cell death was not prevented by caspase antagonists and only partly prevented by nitric-oxide synthase inhibitors. This signal transduction pathway might be a contributing mechanism in ongoing neuronal death in Parkinson disease.Fil: de Erausquin, Gabriel Alejandro. Washington University School of Medicine; Estados UnidosFil: Hyrc, Krzyztof. Washington University School of Medicine; Estados UnidosFil: Dorsey, David A.. Washington University School of Medicine; Estados UnidosFil: Mamah, Daniel. Washington University School of Medicine; Estados UnidosFil: Dokucu, Mehmet. Washington University School of Medicine; Estados UnidosFil: Masco, Daniel Hugo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Walton, Timothy. Washington University School of Medicine; Estados UnidosFil: Dikranian, Krikor. Washington University School of Medicine; Estados UnidosFil: Soriano, Mario. Universidad de Valencia; EspañaFil: Garcia Verdugo, José Manuel. Universidad de Valencia; EspañaFil: Goldberg, Mark P.. Washington University School of Medicine; Estados UnidosFil: Dugan, Laura L.. Washington University School of Medicine; Estados UnidosAmerican Society for Pharmacology and Experimental Therapeutics2003-04-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67178de Erausquin, Gabriel Alejandro; Hyrc, Krzyztof; Dorsey, David A.; Mamah, Daniel; Dokucu, Mehmet; et al.; Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 63; 4; 1-4-2003; 784-7900026-895X1521-0111CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://molpharm.aspetjournals.org/content/63/4/784.longinfo:eu-repo/semantics/altIdentifier/doi/10.1124/mol.63.4.784info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:43Zoai:ri.conicet.gov.ar:11336/67178instacron: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 09:33:43.356CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
title Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
spellingShingle Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
de Erausquin, Gabriel Alejandro
Parkinson Disease
Nuclear Transcription
Cell Death
title_short Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
title_full Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
title_fullStr Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
title_full_unstemmed Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
title_sort Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons
dc.creator.none.fl_str_mv de Erausquin, Gabriel Alejandro
Hyrc, Krzyztof
Dorsey, David A.
Mamah, Daniel
Dokucu, Mehmet
Masco, Daniel Hugo
Walton, Timothy
Dikranian, Krikor
Soriano, Mario
Garcia Verdugo, José Manuel
Goldberg, Mark P.
Dugan, Laura L.
author de Erausquin, Gabriel Alejandro
author_facet de Erausquin, Gabriel Alejandro
Hyrc, Krzyztof
Dorsey, David A.
Mamah, Daniel
Dokucu, Mehmet
Masco, Daniel Hugo
Walton, Timothy
Dikranian, Krikor
Soriano, Mario
Garcia Verdugo, José Manuel
Goldberg, Mark P.
Dugan, Laura L.
author_role author
author2 Hyrc, Krzyztof
Dorsey, David A.
Mamah, Daniel
Dokucu, Mehmet
Masco, Daniel Hugo
Walton, Timothy
Dikranian, Krikor
Soriano, Mario
Garcia Verdugo, José Manuel
Goldberg, Mark P.
Dugan, Laura L.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Parkinson Disease
Nuclear Transcription
Cell Death
topic Parkinson Disease
Nuclear Transcription
Cell Death
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We describe a new molecular mechanism of cell death by excitotoxicity mediated through nuclear transcription factor κB (NFκB) in rat embryonic cultures of dopaminergic neurons. Treatment of mesencephalic cultures with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca2+ monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of NFκB, and transcriptional activation of the oncogenep53. Interruption of any of these steps by specific antagonists prevented neurite pruning and programmed cell death. In contrast, cell death was not prevented by caspase antagonists and only partly prevented by nitric-oxide synthase inhibitors. This signal transduction pathway might be a contributing mechanism in ongoing neuronal death in Parkinson disease.
Fil: de Erausquin, Gabriel Alejandro. Washington University School of Medicine; Estados Unidos
Fil: Hyrc, Krzyztof. Washington University School of Medicine; Estados Unidos
Fil: Dorsey, David A.. Washington University School of Medicine; Estados Unidos
Fil: Mamah, Daniel. Washington University School of Medicine; Estados Unidos
Fil: Dokucu, Mehmet. Washington University School of Medicine; Estados Unidos
Fil: Masco, Daniel Hugo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Walton, Timothy. Washington University School of Medicine; Estados Unidos
Fil: Dikranian, Krikor. Washington University School of Medicine; Estados Unidos
Fil: Soriano, Mario. Universidad de Valencia; España
Fil: Garcia Verdugo, José Manuel. Universidad de Valencia; España
Fil: Goldberg, Mark P.. Washington University School of Medicine; Estados Unidos
Fil: Dugan, Laura L.. Washington University School of Medicine; Estados Unidos
description We describe a new molecular mechanism of cell death by excitotoxicity mediated through nuclear transcription factor κB (NFκB) in rat embryonic cultures of dopaminergic neurons. Treatment of mesencephalic cultures with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca2+ monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of NFκB, and transcriptional activation of the oncogenep53. Interruption of any of these steps by specific antagonists prevented neurite pruning and programmed cell death. In contrast, cell death was not prevented by caspase antagonists and only partly prevented by nitric-oxide synthase inhibitors. This signal transduction pathway might be a contributing mechanism in ongoing neuronal death in Parkinson disease.
publishDate 2003
dc.date.none.fl_str_mv 2003-04-01
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/11336/67178
de Erausquin, Gabriel Alejandro; Hyrc, Krzyztof; Dorsey, David A.; Mamah, Daniel; Dokucu, Mehmet; et al.; Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 63; 4; 1-4-2003; 784-790
0026-895X
1521-0111
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67178
identifier_str_mv de Erausquin, Gabriel Alejandro; Hyrc, Krzyztof; Dorsey, David A.; Mamah, Daniel; Dokucu, Mehmet; et al.; Nuclear translocation of nuclear transcription factor-κB by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 63; 4; 1-4-2003; 784-790
0026-895X
1521-0111
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://molpharm.aspetjournals.org/content/63/4/784.long
info:eu-repo/semantics/altIdentifier/doi/10.1124/mol.63.4.784
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
dc.publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
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_ 1844613038589607936
score 13.070432

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