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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/271953
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:24:23Zoai: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:34982025-09-29 10:24:23.999CONICET 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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1844614240324812800 |
score |
13.070432 |