Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation

Autores
Dasuri, Kalavathi; Ebenezer, Philip J.; Uranga, Romina Maria; Gavilan, Elena; Zhang, Le; Fernandez-Kim, Sun O. K.; Bruce Keller, Annadora J.; Keller, Jeffrey N.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Amino acid analogs promote translational errors that result in aberrant protein synthesis, and have been used to understand the effects of protein misfolding in a variety of physiological and pathological settings. TDP-43 is a protein that is linked to protein aggregation and toxicity in a variety of neurodegenerative diseases. In this study we exposed primary rat neurons and astrocyte cultures to established amino acid analogs (Canavanine and Azetidine-2-carboxylic acid), and observed both cell types undergo a dose-dependent increase in toxicity, with neurons exhibiting a greater degree of toxicity as compared to astrocytes. Neurons and astrocytes exhibited similar increases in ubiquitinated and oxidized protein following analog treatment. Analog treatment increased Heat shock protein (Hsp) levels in both neurons and astrocytes. In neurons, and to a lesser extent astrocytes, the levels of TDP-43 increased in response to analog treatment. Taken together, these data indicate that neurons exhibit preferential toxicity and alterations in TDP-43, in response to increased protein misfolding, as compared to astrocytes.
Fil: Dasuri, Kalavathi. State University Of Louisiana; Estados Unidos
Fil: Ebenezer, Philip J.. State University Of Louisiana; Estados Unidos
Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Gavilan, Elena. Universidad de Sevilla; España
Fil: Zhang, Le. State University Of Louisiana; Estados Unidos
Fil: Fernandez-Kim, Sun O. K.. State University Of Louisiana; Estados Unidos
Fil: Bruce Keller, Annadora J.. State University Of Louisiana; Estados Unidos
Fil: Keller, Jeffrey N.. State University Of Louisiana; Estados Unidos
Materia
NEURON
ASTROCYTE
TDP-43
PROTEIN MISFOLDING
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:11336/6462
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulationDasuri, KalavathiEbenezer, Philip J.Uranga, Romina MariaGavilan, ElenaZhang, LeFernandez-Kim, Sun O. K.Bruce Keller, Annadora J.Keller, Jeffrey N.NEURONASTROCYTETDP-43PROTEIN MISFOLDINGhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Amino acid analogs promote translational errors that result in aberrant protein synthesis, and have been used to understand the effects of protein misfolding in a variety of physiological and pathological settings. TDP-43 is a protein that is linked to protein aggregation and toxicity in a variety of neurodegenerative diseases. In this study we exposed primary rat neurons and astrocyte cultures to established amino acid analogs (Canavanine and Azetidine-2-carboxylic acid), and observed both cell types undergo a dose-dependent increase in toxicity, with neurons exhibiting a greater degree of toxicity as compared to astrocytes. Neurons and astrocytes exhibited similar increases in ubiquitinated and oxidized protein following analog treatment. Analog treatment increased Heat shock protein (Hsp) levels in both neurons and astrocytes. In neurons, and to a lesser extent astrocytes, the levels of TDP-43 increased in response to analog treatment. Taken together, these data indicate that neurons exhibit preferential toxicity and alterations in TDP-43, in response to increased protein misfolding, as compared to astrocytes.Fil: Dasuri, Kalavathi. State University Of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University Of Louisiana; Estados UnidosFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Gavilan, Elena. Universidad de Sevilla; EspañaFil: Zhang, Le. State University Of Louisiana; Estados UnidosFil: Fernandez-Kim, Sun O. K.. State University Of Louisiana; Estados UnidosFil: Bruce Keller, Annadora J.. State University Of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University Of Louisiana; Estados UnidosWiley2011-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6462Dasuri, Kalavathi; Ebenezer, Philip J.; Uranga, Romina Maria; Gavilan, Elena; Zhang, Le; et al.; Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation; Wiley; Journal of Neuroscience Research; 89; 9; 9-2011; 1471-14770360-4012enginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jnr.22677info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175609/info:eu-repo/semantics/altIdentifier/pmid/PMC3175609info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jnr.22677/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:20Zoai:ri.conicet.gov.ar:11336/6462instacron: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:34982025-09-03 10:11:20.361CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
title Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
spellingShingle Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
Dasuri, Kalavathi
NEURON
ASTROCYTE
TDP-43
PROTEIN MISFOLDING
title_short Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
title_full Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
title_fullStr Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
title_full_unstemmed Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
title_sort Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
dc.creator.none.fl_str_mv Dasuri, Kalavathi
Ebenezer, Philip J.
Uranga, Romina Maria
Gavilan, Elena
Zhang, Le
Fernandez-Kim, Sun O. K.
Bruce Keller, Annadora J.
Keller, Jeffrey N.
author Dasuri, Kalavathi
author_facet Dasuri, Kalavathi
Ebenezer, Philip J.
Uranga, Romina Maria
Gavilan, Elena
Zhang, Le
Fernandez-Kim, Sun O. K.
Bruce Keller, Annadora J.
Keller, Jeffrey N.
author_role author
author2 Ebenezer, Philip J.
Uranga, Romina Maria
Gavilan, Elena
Zhang, Le
Fernandez-Kim, Sun O. K.
Bruce Keller, Annadora J.
Keller, Jeffrey N.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NEURON
ASTROCYTE
TDP-43
PROTEIN MISFOLDING
topic NEURON
ASTROCYTE
TDP-43
PROTEIN MISFOLDING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Amino acid analogs promote translational errors that result in aberrant protein synthesis, and have been used to understand the effects of protein misfolding in a variety of physiological and pathological settings. TDP-43 is a protein that is linked to protein aggregation and toxicity in a variety of neurodegenerative diseases. In this study we exposed primary rat neurons and astrocyte cultures to established amino acid analogs (Canavanine and Azetidine-2-carboxylic acid), and observed both cell types undergo a dose-dependent increase in toxicity, with neurons exhibiting a greater degree of toxicity as compared to astrocytes. Neurons and astrocytes exhibited similar increases in ubiquitinated and oxidized protein following analog treatment. Analog treatment increased Heat shock protein (Hsp) levels in both neurons and astrocytes. In neurons, and to a lesser extent astrocytes, the levels of TDP-43 increased in response to analog treatment. Taken together, these data indicate that neurons exhibit preferential toxicity and alterations in TDP-43, in response to increased protein misfolding, as compared to astrocytes.
Fil: Dasuri, Kalavathi. State University Of Louisiana; Estados Unidos
Fil: Ebenezer, Philip J.. State University Of Louisiana; Estados Unidos
Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Gavilan, Elena. Universidad de Sevilla; España
Fil: Zhang, Le. State University Of Louisiana; Estados Unidos
Fil: Fernandez-Kim, Sun O. K.. State University Of Louisiana; Estados Unidos
Fil: Bruce Keller, Annadora J.. State University Of Louisiana; Estados Unidos
Fil: Keller, Jeffrey N.. State University Of Louisiana; Estados Unidos
description Amino acid analogs promote translational errors that result in aberrant protein synthesis, and have been used to understand the effects of protein misfolding in a variety of physiological and pathological settings. TDP-43 is a protein that is linked to protein aggregation and toxicity in a variety of neurodegenerative diseases. In this study we exposed primary rat neurons and astrocyte cultures to established amino acid analogs (Canavanine and Azetidine-2-carboxylic acid), and observed both cell types undergo a dose-dependent increase in toxicity, with neurons exhibiting a greater degree of toxicity as compared to astrocytes. Neurons and astrocytes exhibited similar increases in ubiquitinated and oxidized protein following analog treatment. Analog treatment increased Heat shock protein (Hsp) levels in both neurons and astrocytes. In neurons, and to a lesser extent astrocytes, the levels of TDP-43 increased in response to analog treatment. Taken together, these data indicate that neurons exhibit preferential toxicity and alterations in TDP-43, in response to increased protein misfolding, as compared to astrocytes.
publishDate 2011
dc.date.none.fl_str_mv 2011-09
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/11336/6462
Dasuri, Kalavathi; Ebenezer, Philip J.; Uranga, Romina Maria; Gavilan, Elena; Zhang, Le; et al.; Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation; Wiley; Journal of Neuroscience Research; 89; 9; 9-2011; 1471-1477
0360-4012
url http://hdl.handle.net/11336/6462
identifier_str_mv Dasuri, Kalavathi; Ebenezer, Philip J.; Uranga, Romina Maria; Gavilan, Elena; Zhang, Le; et al.; Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation; Wiley; Journal of Neuroscience Research; 89; 9; 9-2011; 1471-1477
0360-4012
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/jnr.22677
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175609/
info:eu-repo/semantics/altIdentifier/pmid/PMC3175609
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jnr.22677/abstract
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
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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 13.13397

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