Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity

Autores
Conde, Melisa Ailén; Benzi Juncos, Oriana Nicole; Maniscalchi, Athina del Valle; Funk, Melania Iara; Alza, Natalia Paola; Salvador, Gabriela Alejandra
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Epidemiological studies provide evidence of a strong association between the use of dithiocarbamate pesticides, such as Maneb (MB), and the risk of Parkinson’s disease. Here, we tested the hypothesis that MB increases α-synuclein expression and downregulates several redox-sensitive transcription factors, thus promoting neuronal death. For this purpose, we challenged neuronal and primary glial cultures, and mice with MB. When exposed to MB, neurons showed α-synuclein upregulation accompanied by markers of oxidative stress. This was associated with diminished glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 mRNA expression and upregulation of the NRF2 repressor, BACH1. MB treatment also downregulated glutathione peroxidase 4 mRNA levels in neurons, which was coincident with increased content of reactive oxygen species, lipid peroxidation, and mitochondrial alterations. These deleterious effects were prevented by treating MB-exposed neurons with ferrostatin-1, an inhibitor of ferroptosis. In glial cell cultures, MB triggered microglial and astrocyte activation. In mice, MBinduced neurodegeneration provoked motor impairment associated with enhanced αsynuclein expression in midbrain. Our results show that MB-induced neurotoxicity downregulates NRF2 pathway and elicits neuronal death probably triggering mechanisms associated with ferroptosis.
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: Benzi Juncos, Oriana Nicole. 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: Maniscalchi, Athina del Valle. 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: Funk, Melania Iara. 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. Universidad Nacional del Sur. Departamento de Química; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
SAN2023 Annual Meeting
San Luis
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
FERROPTOSIS
MANEB
NEUROTOXICITY
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:11336/227115
Acceder
id CONICETDig_bd1274598d042594964ca0ba395389b1
oai_identifier_str oai:ri.conicet.gov.ar:11336/227115
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicityConde, Melisa AilénBenzi Juncos, Oriana NicoleManiscalchi, Athina del ValleFunk, Melania IaraAlza, Natalia PaolaSalvador, Gabriela AlejandraFERROPTOSISMANEBNEUROTOXICITYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Epidemiological studies provide evidence of a strong association between the use of dithiocarbamate pesticides, such as Maneb (MB), and the risk of Parkinson’s disease. Here, we tested the hypothesis that MB increases α-synuclein expression and downregulates several redox-sensitive transcription factors, thus promoting neuronal death. For this purpose, we challenged neuronal and primary glial cultures, and mice with MB. When exposed to MB, neurons showed α-synuclein upregulation accompanied by markers of oxidative stress. This was associated with diminished glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 mRNA expression and upregulation of the NRF2 repressor, BACH1. MB treatment also downregulated glutathione peroxidase 4 mRNA levels in neurons, which was coincident with increased content of reactive oxygen species, lipid peroxidation, and mitochondrial alterations. These deleterious effects were prevented by treating MB-exposed neurons with ferrostatin-1, an inhibitor of ferroptosis. In glial cell cultures, MB triggered microglial and astrocyte activation. In mice, MBinduced neurodegeneration provoked motor impairment associated with enhanced αsynuclein expression in midbrain. Our results show that MB-induced neurotoxicity downregulates NRF2 pathway and elicits neuronal death probably triggering mechanisms associated with ferroptosis.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: Benzi Juncos, Oriana Nicole. 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: Maniscalchi, Athina del Valle. 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: Funk, Melania Iara. 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; Argentina. Universidad Nacional del Sur. Departamento de Química; 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; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaSAN2023 Annual MeetingSan LuisArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencias2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227115Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity; SAN2023 Annual Meeting; San Luis; Argentina; 2023; 223-223CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://csan2023.saneurociencias.org.ar/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 Técnicas2025-09-03T09:46:04Zoai:ri.conicet.gov.ar:11336/227115instacron: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 09:46:05.013CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
title Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
spellingShingle Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
Conde, Melisa Ailén
FERROPTOSIS
MANEB
NEUROTOXICITY
title_short Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
title_full Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
title_fullStr Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
title_full_unstemmed Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
title_sort Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity
dc.creator.none.fl_str_mv Conde, Melisa Ailén
Benzi Juncos, Oriana Nicole
Maniscalchi, Athina del Valle
Funk, Melania Iara
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author Conde, Melisa Ailén
author_facet Conde, Melisa Ailén
Benzi Juncos, Oriana Nicole
Maniscalchi, Athina del Valle
Funk, Melania Iara
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author_role author
author2 Benzi Juncos, Oriana Nicole
Maniscalchi, Athina del Valle
Funk, Melania Iara
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv FERROPTOSIS
MANEB
NEUROTOXICITY
topic FERROPTOSIS
MANEB
NEUROTOXICITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Epidemiological studies provide evidence of a strong association between the use of dithiocarbamate pesticides, such as Maneb (MB), and the risk of Parkinson’s disease. Here, we tested the hypothesis that MB increases α-synuclein expression and downregulates several redox-sensitive transcription factors, thus promoting neuronal death. For this purpose, we challenged neuronal and primary glial cultures, and mice with MB. When exposed to MB, neurons showed α-synuclein upregulation accompanied by markers of oxidative stress. This was associated with diminished glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 mRNA expression and upregulation of the NRF2 repressor, BACH1. MB treatment also downregulated glutathione peroxidase 4 mRNA levels in neurons, which was coincident with increased content of reactive oxygen species, lipid peroxidation, and mitochondrial alterations. These deleterious effects were prevented by treating MB-exposed neurons with ferrostatin-1, an inhibitor of ferroptosis. In glial cell cultures, MB triggered microglial and astrocyte activation. In mice, MBinduced neurodegeneration provoked motor impairment associated with enhanced αsynuclein expression in midbrain. Our results show that MB-induced neurotoxicity downregulates NRF2 pathway and elicits neuronal death probably triggering mechanisms associated with ferroptosis.
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: Benzi Juncos, Oriana Nicole. 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: Maniscalchi, Athina del Valle. 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: Funk, Melania Iara. 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. Universidad Nacional del Sur. Departamento de Química; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
SAN2023 Annual Meeting
San Luis
Argentina
Sociedad Argentina de Investigación en Neurociencias
description Epidemiological studies provide evidence of a strong association between the use of dithiocarbamate pesticides, such as Maneb (MB), and the risk of Parkinson’s disease. Here, we tested the hypothesis that MB increases α-synuclein expression and downregulates several redox-sensitive transcription factors, thus promoting neuronal death. For this purpose, we challenged neuronal and primary glial cultures, and mice with MB. When exposed to MB, neurons showed α-synuclein upregulation accompanied by markers of oxidative stress. This was associated with diminished glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 mRNA expression and upregulation of the NRF2 repressor, BACH1. MB treatment also downregulated glutathione peroxidase 4 mRNA levels in neurons, which was coincident with increased content of reactive oxygen species, lipid peroxidation, and mitochondrial alterations. These deleterious effects were prevented by treating MB-exposed neurons with ferrostatin-1, an inhibitor of ferroptosis. In glial cell cultures, MB triggered microglial and astrocyte activation. In mice, MBinduced neurodegeneration provoked motor impairment associated with enhanced αsynuclein expression in midbrain. Our results show that MB-induced neurotoxicity downregulates NRF2 pathway and elicits neuronal death probably triggering mechanisms associated with ferroptosis.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
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/11336/227115
Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity; SAN2023 Annual Meeting; San Luis; Argentina; 2023; 223-223
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227115
identifier_str_mv Downregulation of redox-sensitive transcription factors and neuronal ferroptosis as underlynig mechanisms of maneb-induced toxicity; SAN2023 Annual Meeting; San Luis; Argentina; 2023; 223-223
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://csan2023.saneurociencias.org.ar/
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.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
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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