AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity

Autores
Conde, Melisa Ailén; Iglesias Gonzalez,; Alza, Natalia Paola; Benzi Juncos, Oriana Nicole; Uranga, Romina Maria; Salvador, Gabriela Alejandra
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
α-synuclein (α-syn) overexpression and manganese-based pesticides such as Maneb (Mb) have been both implicated as etiological factors of Parkinson‘s disease. We have previously reported the neuroprotective role of Akt/FoxO3a in amyloid β- and Fe-induced injury. In this work, we studied the role of the above-mentioned pathway in the effect of Mb and/or α-syn overexpression on IMR-32 human neuroblastoma cells. For this purpose, we exposed these neurons for different times (24-72 h) to increasing Mb concentrations (6-24 μM) and evaluated the redox status, Akt/FoxO3a subcellular localization and phosphorylation levels, and cell viability. The same parameters were evaluated in neurons stably overexpressing the wild type form of α-syn and exposed to either Mb or its vehicle. Mb exposure provoked a time- and concentration-dependent decrease in neuronal viability. This cytotoxic effect was mediated by the increase in reactive oxygen species (ROS), lipid peroxides and membrane cell permeability (LDH release). Intriguingly, Mb exposure in α-synoverexpressing neurons showed decreased ROS content and LDH release, with no changes in lipid peroxides. Mb was also found to induce changes in α-syn aggregation and phosphorylation, as measured with the intracellular probe Thioflavin S and by immunocytochemistry. On the other hand, Mb exposure and α-syn overexpression unconnectedly triggered the increase in Akt and FoxO3a nuclear localization. However, Mb exposure in α-syn overexpressing neurons enhanced FoxO3a nuclear localization without increasing cell death. We hypothesize that FoxO3a might be an α-syn target related with its unexpected protective role.
Fil: Conde, Melisa Ailén. 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: Iglesias Gonzalez,. 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: Alza, Natalia Paola. 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: Benzi Juncos, Oriana Nicole. Universidad Nacional del Sur; Argentina. 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: 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: 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
54th Annual Meeting Argentine Society for Biochemistry and Molecular Biology
Paraná
Argentina
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
Materia
ALPHA-SYNUCLEIN
MANEB
PARKINSON'S DISEASE
NEURODEGENERATION
NEUROTOXICITY
AKT/FOXO3A
MANCOZEB
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:11336/222946
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/222946
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicityConde, Melisa AilénIglesias Gonzalez,Alza, Natalia PaolaBenzi Juncos, Oriana NicoleUranga, Romina MariaSalvador, Gabriela AlejandraALPHA-SYNUCLEINMANEBPARKINSON'S DISEASENEURODEGENERATIONNEUROTOXICITYAKT/FOXO3AMANCOZEBhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1α-synuclein (α-syn) overexpression and manganese-based pesticides such as Maneb (Mb) have been both implicated as etiological factors of Parkinson‘s disease. We have previously reported the neuroprotective role of Akt/FoxO3a in amyloid β- and Fe-induced injury. In this work, we studied the role of the above-mentioned pathway in the effect of Mb and/or α-syn overexpression on IMR-32 human neuroblastoma cells. For this purpose, we exposed these neurons for different times (24-72 h) to increasing Mb concentrations (6-24 μM) and evaluated the redox status, Akt/FoxO3a subcellular localization and phosphorylation levels, and cell viability. The same parameters were evaluated in neurons stably overexpressing the wild type form of α-syn and exposed to either Mb or its vehicle. Mb exposure provoked a time- and concentration-dependent decrease in neuronal viability. This cytotoxic effect was mediated by the increase in reactive oxygen species (ROS), lipid peroxides and membrane cell permeability (LDH release). Intriguingly, Mb exposure in α-synoverexpressing neurons showed decreased ROS content and LDH release, with no changes in lipid peroxides. Mb was also found to induce changes in α-syn aggregation and phosphorylation, as measured with the intracellular probe Thioflavin S and by immunocytochemistry. On the other hand, Mb exposure and α-syn overexpression unconnectedly triggered the increase in Akt and FoxO3a nuclear localization. However, Mb exposure in α-syn overexpressing neurons enhanced FoxO3a nuclear localization without increasing cell death. We hypothesize that FoxO3a might be an α-syn target related with its unexpected protective role.Fil: Conde, Melisa Ailén. 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: Iglesias Gonzalez,. 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: Alza, Natalia Paola. 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: Benzi Juncos, Oriana Nicole. Universidad Nacional del Sur; Argentina. 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: 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: 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; Argentina54th Annual Meeting Argentine Society for Biochemistry and Molecular BiologyParanáArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularBiocell2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/222946AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity; 54th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; Paraná; Argentina; 2018; 85-850327-95451667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/biocell/v42nSuppl.4/33869/pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:46Zoai:ri.conicet.gov.ar:11336/222946instacron: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 09:35:46.952CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
title AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
spellingShingle AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
Conde, Melisa Ailén
ALPHA-SYNUCLEIN
MANEB
PARKINSON'S DISEASE
NEURODEGENERATION
NEUROTOXICITY
AKT/FOXO3A
MANCOZEB
title_short AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
title_full AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
title_fullStr AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
title_full_unstemmed AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
title_sort AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity
dc.creator.none.fl_str_mv Conde, Melisa Ailén
Iglesias Gonzalez,
Alza, Natalia Paola
Benzi Juncos, Oriana Nicole
Uranga, Romina Maria
Salvador, Gabriela Alejandra
author Conde, Melisa Ailén
author_facet Conde, Melisa Ailén
Iglesias Gonzalez,
Alza, Natalia Paola
Benzi Juncos, Oriana Nicole
Uranga, Romina Maria
Salvador, Gabriela Alejandra
author_role author
author2 Iglesias Gonzalez,
Alza, Natalia Paola
Benzi Juncos, Oriana Nicole
Uranga, Romina Maria
Salvador, Gabriela Alejandra
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ALPHA-SYNUCLEIN
MANEB
PARKINSON'S DISEASE
NEURODEGENERATION
NEUROTOXICITY
AKT/FOXO3A
MANCOZEB
topic ALPHA-SYNUCLEIN
MANEB
PARKINSON'S DISEASE
NEURODEGENERATION
NEUROTOXICITY
AKT/FOXO3A
MANCOZEB
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv α-synuclein (α-syn) overexpression and manganese-based pesticides such as Maneb (Mb) have been both implicated as etiological factors of Parkinson‘s disease. We have previously reported the neuroprotective role of Akt/FoxO3a in amyloid β- and Fe-induced injury. In this work, we studied the role of the above-mentioned pathway in the effect of Mb and/or α-syn overexpression on IMR-32 human neuroblastoma cells. For this purpose, we exposed these neurons for different times (24-72 h) to increasing Mb concentrations (6-24 μM) and evaluated the redox status, Akt/FoxO3a subcellular localization and phosphorylation levels, and cell viability. The same parameters were evaluated in neurons stably overexpressing the wild type form of α-syn and exposed to either Mb or its vehicle. Mb exposure provoked a time- and concentration-dependent decrease in neuronal viability. This cytotoxic effect was mediated by the increase in reactive oxygen species (ROS), lipid peroxides and membrane cell permeability (LDH release). Intriguingly, Mb exposure in α-synoverexpressing neurons showed decreased ROS content and LDH release, with no changes in lipid peroxides. Mb was also found to induce changes in α-syn aggregation and phosphorylation, as measured with the intracellular probe Thioflavin S and by immunocytochemistry. On the other hand, Mb exposure and α-syn overexpression unconnectedly triggered the increase in Akt and FoxO3a nuclear localization. However, Mb exposure in α-syn overexpressing neurons enhanced FoxO3a nuclear localization without increasing cell death. We hypothesize that FoxO3a might be an α-syn target related with its unexpected protective role.
Fil: Conde, Melisa Ailén. 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: Iglesias Gonzalez,. 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: Alza, Natalia Paola. 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: Benzi Juncos, Oriana Nicole. Universidad Nacional del Sur; Argentina. 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: 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: 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
54th Annual Meeting Argentine Society for Biochemistry and Molecular Biology
Paraná
Argentina
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
description α-synuclein (α-syn) overexpression and manganese-based pesticides such as Maneb (Mb) have been both implicated as etiological factors of Parkinson‘s disease. We have previously reported the neuroprotective role of Akt/FoxO3a in amyloid β- and Fe-induced injury. In this work, we studied the role of the above-mentioned pathway in the effect of Mb and/or α-syn overexpression on IMR-32 human neuroblastoma cells. For this purpose, we exposed these neurons for different times (24-72 h) to increasing Mb concentrations (6-24 μM) and evaluated the redox status, Akt/FoxO3a subcellular localization and phosphorylation levels, and cell viability. The same parameters were evaluated in neurons stably overexpressing the wild type form of α-syn and exposed to either Mb or its vehicle. Mb exposure provoked a time- and concentration-dependent decrease in neuronal viability. This cytotoxic effect was mediated by the increase in reactive oxygen species (ROS), lipid peroxides and membrane cell permeability (LDH release). Intriguingly, Mb exposure in α-synoverexpressing neurons showed decreased ROS content and LDH release, with no changes in lipid peroxides. Mb was also found to induce changes in α-syn aggregation and phosphorylation, as measured with the intracellular probe Thioflavin S and by immunocytochemistry. On the other hand, Mb exposure and α-syn overexpression unconnectedly triggered the increase in Akt and FoxO3a nuclear localization. However, Mb exposure in α-syn overexpressing neurons enhanced FoxO3a nuclear localization without increasing cell death. We hypothesize that FoxO3a might be an α-syn target related with its unexpected protective role.
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/11336/222946
AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity; 54th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; Paraná; Argentina; 2018; 85-85
0327-9545
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/222946
identifier_str_mv AKT/FOXO3A pathway: Signaling target α-Synuclein overexpression and maneb mediated neurotoxicity; 54th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; Paraná; Argentina; 2018; 85-85
0327-9545
1667-5746
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/biocell/v42nSuppl.4/33869/pdf
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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