An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk

Autores
Benzi Juncos, Oriana Nicole; Alza, Natalia Paola; Cordero, José; Barrera, Nelson Patricio; Salvador, Gabriela Alejandra
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Environmental neurotoxicants, such as Maneb (MB) and other dithiocarbamate pesticides, trigger chronic neuroin- flammation probably due to defective resolution mecha- nisms, leading to neurodegeneration. The inflammation/ resolution balance is governed by a plethora of special- ized pro-resolving lipid mediators (SPM) that act as li- gands of the GPCR receptor FPR2/ALX. SPM are mainly synthetized by lipoxygenases from arachidonic acid (AA) and docosahexaenoic acid (DHA). Thus, our aim was to study the resolution pathway modulated by FPR2/ALX in response to MB challenge in a context of neuro-glial communication. By metabolomics we detected significant changes in 11 metabolites in neurons and 27 metabolites in astrocytes as a response to MB treatment (p<0.05). In both cell types, phosphatidylcholine was reduced with a simultaneous increase in lysophosphatidylcholine. IPA software’s Path Explorer, Connect and MAP functions re- vealed the upregulation of a secretory phospholipase A2, PLA2G2D. GC-MS fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes (p<0.05). In addition, increased phosphati- dylcholine (DHA/16:0) content in neurons exposed to MB was confirmed by metabolomics. To evaluate resolution events under MB injury in neuron-glia crosstalk, cell-de- rived secretomes and their lipid extracts were used. As- trocyte secretome and its lipid extract were able to revert MB-induced neurotoxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation as well as by the FPR2/ALX antagonist Quin-C7. Neurons secreted ERK1/2 -dependent glial proliferation signals, also inhibited by Quin-C7. The role of lipidome obtained from conditioned media in neuro-glia responses to MB injury confirmed the lipid nature of mediators involved in resolution. Our results show that neurons and astrocytes secrete lipid ligands for FPR2/ALX -mediated resolution in re- sponse to 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 Química; Argentina
Fil: Cordero, José. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile
Fil: Barrera, Nelson Patricio. 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
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
Maneb
resolution
neuron-glia
FPR2/ALX
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:11336/232434
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/232434
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An orphan lipid ligand activates resolution pathways in neuron-glia crosstalkBenzi Juncos, Oriana NicoleAlza, Natalia PaolaCordero, JoséBarrera, Nelson PatricioSalvador, Gabriela AlejandraManebresolutionneuron-gliaFPR2/ALXhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Environmental neurotoxicants, such as Maneb (MB) and other dithiocarbamate pesticides, trigger chronic neuroin- flammation probably due to defective resolution mecha- nisms, leading to neurodegeneration. The inflammation/ resolution balance is governed by a plethora of special- ized pro-resolving lipid mediators (SPM) that act as li- gands of the GPCR receptor FPR2/ALX. SPM are mainly synthetized by lipoxygenases from arachidonic acid (AA) and docosahexaenoic acid (DHA). Thus, our aim was to study the resolution pathway modulated by FPR2/ALX in response to MB challenge in a context of neuro-glial communication. By metabolomics we detected significant changes in 11 metabolites in neurons and 27 metabolites in astrocytes as a response to MB treatment (p<0.05). In both cell types, phosphatidylcholine was reduced with a simultaneous increase in lysophosphatidylcholine. IPA software’s Path Explorer, Connect and MAP functions re- vealed the upregulation of a secretory phospholipase A2, PLA2G2D. GC-MS fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes (p<0.05). In addition, increased phosphati- dylcholine (DHA/16:0) content in neurons exposed to MB was confirmed by metabolomics. To evaluate resolution events under MB injury in neuron-glia crosstalk, cell-de- rived secretomes and their lipid extracts were used. As- trocyte secretome and its lipid extract were able to revert MB-induced neurotoxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation as well as by the FPR2/ALX antagonist Quin-C7. Neurons secreted ERK1/2 -dependent glial proliferation signals, also inhibited by Quin-C7. The role of lipidome obtained from conditioned media in neuro-glia responses to MB injury confirmed the lipid nature of mediators involved in resolution. Our results show that neurons and astrocytes secrete lipid ligands for FPR2/ALX -mediated resolution in re- sponse to 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; 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: Cordero, José. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; ChileFil: Barrera, Nelson Patricio. 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; ArgentinaLXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de BiologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista Medicina2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/232434An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 64-640025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol83-23/s5/1s5.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 Técnicas2025-10-15T15:20:28Zoai:ri.conicet.gov.ar:11336/232434instacron: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 15:20:28.304CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
title An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
spellingShingle An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
Benzi Juncos, Oriana Nicole
Maneb
resolution
neuron-glia
FPR2/ALX
title_short An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
title_full An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
title_fullStr An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
title_full_unstemmed An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
title_sort An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
dc.creator.none.fl_str_mv Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Cordero, José
Barrera, Nelson Patricio
Salvador, Gabriela Alejandra
author Benzi Juncos, Oriana Nicole
author_facet Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Cordero, José
Barrera, Nelson Patricio
Salvador, Gabriela Alejandra
author_role author
author2 Alza, Natalia Paola
Cordero, José
Barrera, Nelson Patricio
Salvador, Gabriela Alejandra
author2_role author
author
author
author
dc.subject.none.fl_str_mv Maneb
resolution
neuron-glia
FPR2/ALX
topic Maneb
resolution
neuron-glia
FPR2/ALX
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 neurotoxicants, such as Maneb (MB) and other dithiocarbamate pesticides, trigger chronic neuroin- flammation probably due to defective resolution mecha- nisms, leading to neurodegeneration. The inflammation/ resolution balance is governed by a plethora of special- ized pro-resolving lipid mediators (SPM) that act as li- gands of the GPCR receptor FPR2/ALX. SPM are mainly synthetized by lipoxygenases from arachidonic acid (AA) and docosahexaenoic acid (DHA). Thus, our aim was to study the resolution pathway modulated by FPR2/ALX in response to MB challenge in a context of neuro-glial communication. By metabolomics we detected significant changes in 11 metabolites in neurons and 27 metabolites in astrocytes as a response to MB treatment (p<0.05). In both cell types, phosphatidylcholine was reduced with a simultaneous increase in lysophosphatidylcholine. IPA software’s Path Explorer, Connect and MAP functions re- vealed the upregulation of a secretory phospholipase A2, PLA2G2D. GC-MS fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes (p<0.05). In addition, increased phosphati- dylcholine (DHA/16:0) content in neurons exposed to MB was confirmed by metabolomics. To evaluate resolution events under MB injury in neuron-glia crosstalk, cell-de- rived secretomes and their lipid extracts were used. As- trocyte secretome and its lipid extract were able to revert MB-induced neurotoxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation as well as by the FPR2/ALX antagonist Quin-C7. Neurons secreted ERK1/2 -dependent glial proliferation signals, also inhibited by Quin-C7. The role of lipidome obtained from conditioned media in neuro-glia responses to MB injury confirmed the lipid nature of mediators involved in resolution. Our results show that neurons and astrocytes secrete lipid ligands for FPR2/ALX -mediated resolution in re- sponse to 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 Química; Argentina
Fil: Cordero, José. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile
Fil: Barrera, Nelson Patricio. 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
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Environmental neurotoxicants, such as Maneb (MB) and other dithiocarbamate pesticides, trigger chronic neuroin- flammation probably due to defective resolution mecha- nisms, leading to neurodegeneration. The inflammation/ resolution balance is governed by a plethora of special- ized pro-resolving lipid mediators (SPM) that act as li- gands of the GPCR receptor FPR2/ALX. SPM are mainly synthetized by lipoxygenases from arachidonic acid (AA) and docosahexaenoic acid (DHA). Thus, our aim was to study the resolution pathway modulated by FPR2/ALX in response to MB challenge in a context of neuro-glial communication. By metabolomics we detected significant changes in 11 metabolites in neurons and 27 metabolites in astrocytes as a response to MB treatment (p<0.05). In both cell types, phosphatidylcholine was reduced with a simultaneous increase in lysophosphatidylcholine. IPA software’s Path Explorer, Connect and MAP functions re- vealed the upregulation of a secretory phospholipase A2, PLA2G2D. GC-MS fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes (p<0.05). In addition, increased phosphati- dylcholine (DHA/16:0) content in neurons exposed to MB was confirmed by metabolomics. To evaluate resolution events under MB injury in neuron-glia crosstalk, cell-de- rived secretomes and their lipid extracts were used. As- trocyte secretome and its lipid extract were able to revert MB-induced neurotoxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation as well as by the FPR2/ALX antagonist Quin-C7. Neurons secreted ERK1/2 -dependent glial proliferation signals, also inhibited by Quin-C7. The role of lipidome obtained from conditioned media in neuro-glia responses to MB injury confirmed the lipid nature of mediators involved in resolution. Our results show that neurons and astrocytes secrete lipid ligands for FPR2/ALX -mediated resolution in re- sponse to MB toxicity.
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
Reunión
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/11336/232434
An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 64-64
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/232434
identifier_str_mv An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 64-64
0025-7680
1669-9106
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://medicinabuenosaires.com/revistas/vol83-23/s5/1s5.pdf
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 Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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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