Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats

Autores
Uranga, Romina Maria; Giusto, Norma Maria; Salvador, Gabriela Alejandra
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this work we study the state of phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK3 beta) signaling during oxidative injury triggered by free iron using cerebral cortex synaptic endings isolated from adult (4-month-old) and aged (28-month-old) rats. Synaptosomes were exposed to FeSO4 (50 microM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3 beta pathway were evaluated in adult and aged animals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative stress. In adults, Akt was activated after a brief exposure time (5 min), whereas in aged animals activation occurred after 5 and 30 min of incubation with the metal ion. GSK3 beta phosphorylation showed the same activation pattern as that observed for Akt. Both Akt and GSK3 beta phosphorylation were dependent on PI3K activation. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was temporally coincident with Akt activation and was PI3K dependent in adults, whereas ERK1/2 activation in aged rats was higher than that observed in adults and showed no dependence on PI3K activity. We demonstrate here that synaptic endings from adult and aged animals subjected to iron-induced neurotoxicity show a differential profile in the activation of PI3K/Akt/GSK3 beta. Our results strongly suggest that the increased susceptibility of aged animals to oxidative injury provokes a differential modulation of key signaling pathways involved in synaptic plasticity and neuronal survival
Fil: Uranga, Romina Maria. 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: Giusto, Norma Maria. 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: Salvador, Gabriela Alejandra. 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
Iron
Oxidative Stress
Pi3k
Synaptic Endings
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:11336/42019
Acceder
id CONICETDig_9a9542dec21350e42a4ba68679d35a01
oai_identifier_str oai:ri.conicet.gov.ar:11336/42019
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged RatsUranga, Romina MariaGiusto, Norma MariaSalvador, Gabriela AlejandraIronOxidative StressPi3kSynaptic Endingshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In this work we study the state of phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK3 beta) signaling during oxidative injury triggered by free iron using cerebral cortex synaptic endings isolated from adult (4-month-old) and aged (28-month-old) rats. Synaptosomes were exposed to FeSO4 (50 microM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3 beta pathway were evaluated in adult and aged animals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative stress. In adults, Akt was activated after a brief exposure time (5 min), whereas in aged animals activation occurred after 5 and 30 min of incubation with the metal ion. GSK3 beta phosphorylation showed the same activation pattern as that observed for Akt. Both Akt and GSK3 beta phosphorylation were dependent on PI3K activation. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was temporally coincident with Akt activation and was PI3K dependent in adults, whereas ERK1/2 activation in aged rats was higher than that observed in adults and showed no dependence on PI3K activity. We demonstrate here that synaptic endings from adult and aged animals subjected to iron-induced neurotoxicity show a differential profile in the activation of PI3K/Akt/GSK3 beta. Our results strongly suggest that the increased susceptibility of aged animals to oxidative injury provokes a differential modulation of key signaling pathways involved in synaptic plasticity and neuronal survivalFil: Uranga, Romina Maria. 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: Giusto, Norma Maria. 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: Salvador, Gabriela Alejandra. 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; ArgentinaOxford University Press2009-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42019Uranga, Romina Maria; Giusto, Norma Maria; Salvador, Gabriela Alejandra; Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats; Oxford University Press; Toxicological Sciences; 111; 2; 10-2009; 331-3441096-6080CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfp152info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/toxsci/article/111/2/331/1641924info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:35:24Zoai:ri.conicet.gov.ar:11336/42019instacron: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 11:35:24.645CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
title Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
spellingShingle Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
Uranga, Romina Maria
Iron
Oxidative Stress
Pi3k
Synaptic Endings
title_short Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
title_full Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
title_fullStr Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
title_full_unstemmed Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
title_sort Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats
dc.creator.none.fl_str_mv Uranga, Romina Maria
Giusto, Norma Maria
Salvador, Gabriela Alejandra
author Uranga, Romina Maria
author_facet Uranga, Romina Maria
Giusto, Norma Maria
Salvador, Gabriela Alejandra
author_role author
author2 Giusto, Norma Maria
Salvador, Gabriela Alejandra
author2_role author
author
dc.subject.none.fl_str_mv Iron
Oxidative Stress
Pi3k
Synaptic Endings
topic Iron
Oxidative Stress
Pi3k
Synaptic Endings
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In this work we study the state of phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK3 beta) signaling during oxidative injury triggered by free iron using cerebral cortex synaptic endings isolated from adult (4-month-old) and aged (28-month-old) rats. Synaptosomes were exposed to FeSO4 (50 microM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3 beta pathway were evaluated in adult and aged animals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative stress. In adults, Akt was activated after a brief exposure time (5 min), whereas in aged animals activation occurred after 5 and 30 min of incubation with the metal ion. GSK3 beta phosphorylation showed the same activation pattern as that observed for Akt. Both Akt and GSK3 beta phosphorylation were dependent on PI3K activation. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was temporally coincident with Akt activation and was PI3K dependent in adults, whereas ERK1/2 activation in aged rats was higher than that observed in adults and showed no dependence on PI3K activity. We demonstrate here that synaptic endings from adult and aged animals subjected to iron-induced neurotoxicity show a differential profile in the activation of PI3K/Akt/GSK3 beta. Our results strongly suggest that the increased susceptibility of aged animals to oxidative injury provokes a differential modulation of key signaling pathways involved in synaptic plasticity and neuronal survival
Fil: Uranga, Romina Maria. 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: Giusto, Norma Maria. 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: Salvador, Gabriela Alejandra. 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 In this work we study the state of phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK3 beta) signaling during oxidative injury triggered by free iron using cerebral cortex synaptic endings isolated from adult (4-month-old) and aged (28-month-old) rats. Synaptosomes were exposed to FeSO4 (50 microM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3 beta pathway were evaluated in adult and aged animals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative stress. In adults, Akt was activated after a brief exposure time (5 min), whereas in aged animals activation occurred after 5 and 30 min of incubation with the metal ion. GSK3 beta phosphorylation showed the same activation pattern as that observed for Akt. Both Akt and GSK3 beta phosphorylation were dependent on PI3K activation. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was temporally coincident with Akt activation and was PI3K dependent in adults, whereas ERK1/2 activation in aged rats was higher than that observed in adults and showed no dependence on PI3K activity. We demonstrate here that synaptic endings from adult and aged animals subjected to iron-induced neurotoxicity show a differential profile in the activation of PI3K/Akt/GSK3 beta. Our results strongly suggest that the increased susceptibility of aged animals to oxidative injury provokes a differential modulation of key signaling pathways involved in synaptic plasticity and neuronal survival
publishDate 2009
dc.date.none.fl_str_mv 2009-10
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/11336/42019
Uranga, Romina Maria; Giusto, Norma Maria; Salvador, Gabriela Alejandra; Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats; Oxford University Press; Toxicological Sciences; 111; 2; 10-2009; 331-344
1096-6080
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42019
identifier_str_mv Uranga, Romina Maria; Giusto, Norma Maria; Salvador, Gabriela Alejandra; Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3β Pathway in Synaptic Endings from Adult and Aged Rats; Oxford University Press; Toxicological Sciences; 111; 2; 10-2009; 331-344
1096-6080
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfp152
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/toxsci/article/111/2/331/1641924
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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 12.982451

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