Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration

Autores
Conde, Melisa Ailén; Benzi Juncos, Oriana Nicole; Maniscalchi Velásquez, Athina del Valle; Funk, Melania Iar; Bonjour, Mariel; Alza, Natalia Paola; Salvador, Gabriela Alejandra
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
A recently described form of regulated cell death named ferroptosis has been associated with several neurodegenerative processes. The most prominent mechanisms related to ferroptosis are iron accumulation, lipid peroxidation, and mitochondrial disorganization associated with glutathione (GSH) depletion. We aimed to investigate the effect of well-known antioxidants in the above-described mechanisms related to neuronal death by ferroptosis. To this end, we used the pesticide maneb which has been described as a pro-ferroptotic stimulus and whose exposure is associated with Parkinsonism. We found that maneb can trigger dopaminergic neuronal death in a time- and concentration-dependent manner (p<0.01). Neuronal death was accompanied by diminished GSH content (p<0.05), and the typical mitochondrial pattern of ferroptosis (p<0.001). Moreover, maneb treatment was able to increase neuronal alpha-synuclein (aSyn) expression (p<0.05). Using this neurodegenerative framework, we evaluated two different antioxidants: N-acetylcysteine (NAC), a GSH precursor, and ferrostatin-1, a radical-trapping agent. We found that NAC was able to revert aSyn overexpression in maneb-exposed neurons (p<0.05) and that ferrostatin-1 was able to re-establish mitochondrial architecture to that of control neurons (p<0.001). Intriguingly, luteolin, a flavonoid that acts as a free radical scavenger, increased cell death in neurons exposed to maneb (p<0.05). This later could be explained by the inhibitory effect of lipoxygenases exerted by luteolin. Our results show that antioxidants with different mechanisms of action target several steps of ferroptosis, and could be the starting point for further studies aimed at preventing neuronal death by this form of regulated cell death
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 Velásquez, 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 Iar. 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: Bonjour, Mariel. 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
LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina De Farmacología Experimental
Universidad Nacional del Sur
Materia
ANTIOXIDANTS
FERROPTOSIS
NEURODEGENERATION
PESTICIDE
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:11336/278618
Acceder
id CONICETDig_fb0e64bc114186565897a286f45eade5
oai_identifier_str oai:ri.conicet.gov.ar:11336/278618
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With NeurodegenerationConde, Melisa AilénBenzi Juncos, Oriana NicoleManiscalchi Velásquez, Athina del ValleFunk, Melania IarBonjour, MarielAlza, Natalia PaolaSalvador, Gabriela AlejandraANTIOXIDANTSFERROPTOSISNEURODEGENERATIONPESTICIDEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A recently described form of regulated cell death named ferroptosis has been associated with several neurodegenerative processes. The most prominent mechanisms related to ferroptosis are iron accumulation, lipid peroxidation, and mitochondrial disorganization associated with glutathione (GSH) depletion. We aimed to investigate the effect of well-known antioxidants in the above-described mechanisms related to neuronal death by ferroptosis. To this end, we used the pesticide maneb which has been described as a pro-ferroptotic stimulus and whose exposure is associated with Parkinsonism. We found that maneb can trigger dopaminergic neuronal death in a time- and concentration-dependent manner (p<0.01). Neuronal death was accompanied by diminished GSH content (p<0.05), and the typical mitochondrial pattern of ferroptosis (p<0.001). Moreover, maneb treatment was able to increase neuronal alpha-synuclein (aSyn) expression (p<0.05). Using this neurodegenerative framework, we evaluated two different antioxidants: N-acetylcysteine (NAC), a GSH precursor, and ferrostatin-1, a radical-trapping agent. We found that NAC was able to revert aSyn overexpression in maneb-exposed neurons (p<0.05) and that ferrostatin-1 was able to re-establish mitochondrial architecture to that of control neurons (p<0.001). Intriguingly, luteolin, a flavonoid that acts as a free radical scavenger, increased cell death in neurons exposed to maneb (p<0.05). This later could be explained by the inhibitory effect of lipoxygenases exerted by luteolin. Our results show that antioxidants with different mechanisms of action target several steps of ferroptosis, and could be the starting point for further studies aimed at preventing neuronal death by this form of regulated cell deathFil: 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 Velásquez, 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 Iar. 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: Bonjour, Mariel. 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; ArgentinaLVI Reunión Anual De La Asociación Argentina De Farmacología ExperimentalBahía BlancaArgentinaAsociación Argentina De Farmacología ExperimentalUniversidad Nacional del SurAsociación Argentina De Farmacología Experimental2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278618Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental; Bahía Blanca; Argentina; 2024; 112-112CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/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 Técnicas2026-02-26T10:03:19Zoai:ri.conicet.gov.ar:11336/278618instacron: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:34982026-02-26 10:03:20.033CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
title Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
spellingShingle Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
Conde, Melisa Ailén
ANTIOXIDANTS
FERROPTOSIS
NEURODEGENERATION
PESTICIDE
title_short Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
title_full Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
title_fullStr Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
title_full_unstemmed Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
title_sort Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration
dc.creator.none.fl_str_mv Conde, Melisa Ailén
Benzi Juncos, Oriana Nicole
Maniscalchi Velásquez, Athina del Valle
Funk, Melania Iar
Bonjour, Mariel
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author Conde, Melisa Ailén
author_facet Conde, Melisa Ailén
Benzi Juncos, Oriana Nicole
Maniscalchi Velásquez, Athina del Valle
Funk, Melania Iar
Bonjour, Mariel
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author_role author
author2 Benzi Juncos, Oriana Nicole
Maniscalchi Velásquez, Athina del Valle
Funk, Melania Iar
Bonjour, Mariel
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTIOXIDANTS
FERROPTOSIS
NEURODEGENERATION
PESTICIDE
topic ANTIOXIDANTS
FERROPTOSIS
NEURODEGENERATION
PESTICIDE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A recently described form of regulated cell death named ferroptosis has been associated with several neurodegenerative processes. The most prominent mechanisms related to ferroptosis are iron accumulation, lipid peroxidation, and mitochondrial disorganization associated with glutathione (GSH) depletion. We aimed to investigate the effect of well-known antioxidants in the above-described mechanisms related to neuronal death by ferroptosis. To this end, we used the pesticide maneb which has been described as a pro-ferroptotic stimulus and whose exposure is associated with Parkinsonism. We found that maneb can trigger dopaminergic neuronal death in a time- and concentration-dependent manner (p<0.01). Neuronal death was accompanied by diminished GSH content (p<0.05), and the typical mitochondrial pattern of ferroptosis (p<0.001). Moreover, maneb treatment was able to increase neuronal alpha-synuclein (aSyn) expression (p<0.05). Using this neurodegenerative framework, we evaluated two different antioxidants: N-acetylcysteine (NAC), a GSH precursor, and ferrostatin-1, a radical-trapping agent. We found that NAC was able to revert aSyn overexpression in maneb-exposed neurons (p<0.05) and that ferrostatin-1 was able to re-establish mitochondrial architecture to that of control neurons (p<0.001). Intriguingly, luteolin, a flavonoid that acts as a free radical scavenger, increased cell death in neurons exposed to maneb (p<0.05). This later could be explained by the inhibitory effect of lipoxygenases exerted by luteolin. Our results show that antioxidants with different mechanisms of action target several steps of ferroptosis, and could be the starting point for further studies aimed at preventing neuronal death by this form of regulated cell death
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 Velásquez, 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 Iar. 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: Bonjour, Mariel. 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
LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina De Farmacología Experimental
Universidad Nacional del Sur
description A recently described form of regulated cell death named ferroptosis has been associated with several neurodegenerative processes. The most prominent mechanisms related to ferroptosis are iron accumulation, lipid peroxidation, and mitochondrial disorganization associated with glutathione (GSH) depletion. We aimed to investigate the effect of well-known antioxidants in the above-described mechanisms related to neuronal death by ferroptosis. To this end, we used the pesticide maneb which has been described as a pro-ferroptotic stimulus and whose exposure is associated with Parkinsonism. We found that maneb can trigger dopaminergic neuronal death in a time- and concentration-dependent manner (p<0.01). Neuronal death was accompanied by diminished GSH content (p<0.05), and the typical mitochondrial pattern of ferroptosis (p<0.001). Moreover, maneb treatment was able to increase neuronal alpha-synuclein (aSyn) expression (p<0.05). Using this neurodegenerative framework, we evaluated two different antioxidants: N-acetylcysteine (NAC), a GSH precursor, and ferrostatin-1, a radical-trapping agent. We found that NAC was able to revert aSyn overexpression in maneb-exposed neurons (p<0.05) and that ferrostatin-1 was able to re-establish mitochondrial architecture to that of control neurons (p<0.001). Intriguingly, luteolin, a flavonoid that acts as a free radical scavenger, increased cell death in neurons exposed to maneb (p<0.05). This later could be explained by the inhibitory effect of lipoxygenases exerted by luteolin. Our results show that antioxidants with different mechanisms of action target several steps of ferroptosis, and could be the starting point for further studies aimed at preventing neuronal death by this form of regulated cell death
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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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/11336/278618
Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental; Bahía Blanca; Argentina; 2024; 112-112
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278618
identifier_str_mv Different Antioxidants Modulate Several Steps Of Ferroptosis Associated With Neurodegeneration; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental; Bahía Blanca; Argentina; 2024; 112-112
CONICET Digital
CONICET
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language eng
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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/
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Asociación Argentina De Farmacología Experimental
publisher.none.fl_str_mv Asociación Argentina De Farmacología Experimental
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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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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