Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity

Autores
Benzi Juncos, Oriana Nicole; Alza, Natalia Paola; Cordero, José L.; Barrera, Nelson P.; Salvador, Gabriela Alejandra
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Environmental toxicants such as maneb (MB), a dithiocarbamate pesticide, trigger progressive neuronal death, probably due to the imbalance in inflammation/resolution mechanisms, resulting in the onset of neurodegeneration. The inflamma- tion/resolution balance is governed by G protein-coupled receptor (GPCR) signaling, but it has been poorly described in the Central Nervous System (CNS), since resolution GPCR ligands are negligible and elusive lipid compounds. These mediators are mainly synthesized by lipoxygenases (ALOX) from arachidonic acid (AA) and docosahexaenoic acid (DHA) released by specific phospholipases A2 (PLA2). Thus, we aimed to characterize the molecular components of resolution involved in neuron-astrocyte communication in response to MB-induced toxicity. The metabolomics study showed sig- nificant changes in 20 metabolites in neurons and 43 in astrocytes as a response to MB treatment. Major phospholipids’ content (phosphatidylcholine - PC - and phosphatidylethanolamine) was reduced in both cell types with a simultaneous increase in lysophospholipids. In silico analysis revealed the upregulation of a Group IID secretory phospholipase A2 (sPLA2-IID), and the fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes. In addition, increased DHA esterified-PC content in neurons exposed to MB was observed. Astrocyte secretome and its lipid extract protected neurons against MB-induced toxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation by ALOX-15 and associated with the activation of the formyl peptide receptor 2 (FPR2/ALX), probably mediated by lipoxin A4. Moreover, a neuronal lipid ligand induced astrocyte proliferation through this GPCR. Our study suggests that molecular components of the FPR2/ALX pathway participate in both the neuroprotection exerted by astrocytes and astrocytic proliferative signals shaped by neurons under MB toxicity
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: 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 Biología, Bioquímica y Farmacia; Argentina
Fil: Cordero, José L.. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile
Fil: Barrera, Nelson P.. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile
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
Materia
Resolution
neuron-astrocyte crosstalk
DHA/AA Ratio
sPLA2-IID
FPR2/ALX
ALOX-15
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:11336/271953
Acceder
id CONICETDig_01b23df05e977c60860beee32b33775e
oai_identifier_str oai:ri.conicet.gov.ar:11336/271953
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicityBenzi Juncos, Oriana NicoleAlza, Natalia PaolaCordero, José L.Barrera, Nelson P.Salvador, Gabriela AlejandraResolutionneuron-astrocyte crosstalkDHA/AA RatiosPLA2-IIDFPR2/ALXALOX-15https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Environmental toxicants such as maneb (MB), a dithiocarbamate pesticide, trigger progressive neuronal death, probably due to the imbalance in inflammation/resolution mechanisms, resulting in the onset of neurodegeneration. The inflamma- tion/resolution balance is governed by G protein-coupled receptor (GPCR) signaling, but it has been poorly described in the Central Nervous System (CNS), since resolution GPCR ligands are negligible and elusive lipid compounds. These mediators are mainly synthesized by lipoxygenases (ALOX) from arachidonic acid (AA) and docosahexaenoic acid (DHA) released by specific phospholipases A2 (PLA2). Thus, we aimed to characterize the molecular components of resolution involved in neuron-astrocyte communication in response to MB-induced toxicity. The metabolomics study showed sig- nificant changes in 20 metabolites in neurons and 43 in astrocytes as a response to MB treatment. Major phospholipids’ content (phosphatidylcholine - PC - and phosphatidylethanolamine) was reduced in both cell types with a simultaneous increase in lysophospholipids. In silico analysis revealed the upregulation of a Group IID secretory phospholipase A2 (sPLA2-IID), and the fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes. In addition, increased DHA esterified-PC content in neurons exposed to MB was observed. Astrocyte secretome and its lipid extract protected neurons against MB-induced toxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation by ALOX-15 and associated with the activation of the formyl peptide receptor 2 (FPR2/ALX), probably mediated by lipoxin A4. Moreover, a neuronal lipid ligand induced astrocyte proliferation through this GPCR. Our study suggests that molecular components of the FPR2/ALX pathway participate in both the neuroprotection exerted by astrocytes and astrocytic proliferative signals shaped by neurons under MB toxicityFil: 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: 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 Biología, Bioquímica y Farmacia; ArgentinaFil: Cordero, José L.. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; ChileFil: Barrera, Nelson P.. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; ChileFil: 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; ArgentinaSpringer Science2025-08-31info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/271953Benzi Juncos, Oriana Nicole; Alza, Natalia Paola; Cordero, José L.; Barrera, Nelson P.; Salvador, Gabriela Alejandra; Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity; Springer Science; Cellular and Molecular Life Sciences; 82; 31-8-2025; 1-191420-682X1420-9071CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/10.1007/s00018-025-05841-3info:eu-repo/semantics/altIdentifier/doi/10.1007/s00018-025-05841-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:21:33Zoai:ri.conicet.gov.ar:11336/271953instacron: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:34982025-10-15 15:21:33.747CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
title Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
spellingShingle Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
Benzi Juncos, Oriana Nicole
Resolution
neuron-astrocyte crosstalk
DHA/AA Ratio
sPLA2-IID
FPR2/ALX
ALOX-15
title_short Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
title_full Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
title_fullStr Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
title_full_unstemmed Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
title_sort Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity
dc.creator.none.fl_str_mv Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Cordero, José L.
Barrera, Nelson P.
Salvador, Gabriela Alejandra
author Benzi Juncos, Oriana Nicole
author_facet Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Cordero, José L.
Barrera, Nelson P.
Salvador, Gabriela Alejandra
author_role author
author2 Alza, Natalia Paola
Cordero, José L.
Barrera, Nelson P.
Salvador, Gabriela Alejandra
author2_role author
author
author
author
dc.subject.none.fl_str_mv Resolution
neuron-astrocyte crosstalk
DHA/AA Ratio
sPLA2-IID
FPR2/ALX
ALOX-15
topic Resolution
neuron-astrocyte crosstalk
DHA/AA Ratio
sPLA2-IID
FPR2/ALX
ALOX-15
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Environmental toxicants such as maneb (MB), a dithiocarbamate pesticide, trigger progressive neuronal death, probably due to the imbalance in inflammation/resolution mechanisms, resulting in the onset of neurodegeneration. The inflamma- tion/resolution balance is governed by G protein-coupled receptor (GPCR) signaling, but it has been poorly described in the Central Nervous System (CNS), since resolution GPCR ligands are negligible and elusive lipid compounds. These mediators are mainly synthesized by lipoxygenases (ALOX) from arachidonic acid (AA) and docosahexaenoic acid (DHA) released by specific phospholipases A2 (PLA2). Thus, we aimed to characterize the molecular components of resolution involved in neuron-astrocyte communication in response to MB-induced toxicity. The metabolomics study showed sig- nificant changes in 20 metabolites in neurons and 43 in astrocytes as a response to MB treatment. Major phospholipids’ content (phosphatidylcholine - PC - and phosphatidylethanolamine) was reduced in both cell types with a simultaneous increase in lysophospholipids. In silico analysis revealed the upregulation of a Group IID secretory phospholipase A2 (sPLA2-IID), and the fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes. In addition, increased DHA esterified-PC content in neurons exposed to MB was observed. Astrocyte secretome and its lipid extract protected neurons against MB-induced toxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation by ALOX-15 and associated with the activation of the formyl peptide receptor 2 (FPR2/ALX), probably mediated by lipoxin A4. Moreover, a neuronal lipid ligand induced astrocyte proliferation through this GPCR. Our study suggests that molecular components of the FPR2/ALX pathway participate in both the neuroprotection exerted by astrocytes and astrocytic proliferative signals shaped by neurons under MB toxicity
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: 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 Biología, Bioquímica y Farmacia; Argentina
Fil: Cordero, José L.. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile
Fil: Barrera, Nelson P.. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile
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
description Environmental toxicants such as maneb (MB), a dithiocarbamate pesticide, trigger progressive neuronal death, probably due to the imbalance in inflammation/resolution mechanisms, resulting in the onset of neurodegeneration. The inflamma- tion/resolution balance is governed by G protein-coupled receptor (GPCR) signaling, but it has been poorly described in the Central Nervous System (CNS), since resolution GPCR ligands are negligible and elusive lipid compounds. These mediators are mainly synthesized by lipoxygenases (ALOX) from arachidonic acid (AA) and docosahexaenoic acid (DHA) released by specific phospholipases A2 (PLA2). Thus, we aimed to characterize the molecular components of resolution involved in neuron-astrocyte communication in response to MB-induced toxicity. The metabolomics study showed sig- nificant changes in 20 metabolites in neurons and 43 in astrocytes as a response to MB treatment. Major phospholipids’ content (phosphatidylcholine - PC - and phosphatidylethanolamine) was reduced in both cell types with a simultaneous increase in lysophospholipids. In silico analysis revealed the upregulation of a Group IID secretory phospholipase A2 (sPLA2-IID), and the fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes. In addition, increased DHA esterified-PC content in neurons exposed to MB was observed. Astrocyte secretome and its lipid extract protected neurons against MB-induced toxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation by ALOX-15 and associated with the activation of the formyl peptide receptor 2 (FPR2/ALX), probably mediated by lipoxin A4. Moreover, a neuronal lipid ligand induced astrocyte proliferation through this GPCR. Our study suggests that molecular components of the FPR2/ALX pathway participate in both the neuroprotection exerted by astrocytes and astrocytic proliferative signals shaped by neurons under MB toxicity
publishDate 2025
dc.date.none.fl_str_mv 2025-08-31
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/11336/271953
Benzi Juncos, Oriana Nicole; Alza, Natalia Paola; Cordero, José L.; Barrera, Nelson P.; Salvador, Gabriela Alejandra; Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity; Springer Science; Cellular and Molecular Life Sciences; 82; 31-8-2025; 1-19
1420-682X
1420-9071
CONICET Digital
CONICET
url http://hdl.handle.net/11336/271953
identifier_str_mv Benzi Juncos, Oriana Nicole; Alza, Natalia Paola; Cordero, José L.; Barrera, Nelson P.; Salvador, Gabriela Alejandra; Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity; Springer Science; Cellular and Molecular Life Sciences; 82; 31-8-2025; 1-19
1420-682X
1420-9071
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://link.springer.com/10.1007/s00018-025-05841-3
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00018-025-05841-3
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.publisher.none.fl_str_mv Springer Science
publisher.none.fl_str_mv Springer Science
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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