FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity

Autores
Benzi Juncos, Oriana Nicole; Alza, Natalia Paola; Salvador, Gabriela Alejandra
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Neurotoxicity generated by several environmental factors has been widely associated with Parkinson’s disease (PD). Human prolonged exposure to the pesticide Maneb (MB) has been reported as a triggering insult for dopaminergic neurodegeneration and the onset of PD. Even though this effect has been well documented in numerous epidemiological and research studies, little is yet known about the mechanisms underlying MB neurotoxicity in neuron-glia crosstalk. Based on our previous reports about the involvement of cyclooxygenases (COX) and lipoxygenases (LOX) in the neuronal response to MB toxicity (SAIB2021), our aim was to elucidate the role of these lipid mediators’ pathways in neuron-glia communication. To study the possible alterations in neuron-glia crosstalk caused by MB exposure, dopaminergic N27 cells were exposed to astrocyte (C6 cell line) secretome and vice versa. Astrocytes’ secretome showed to be neuroprotective against MB, whereas neurons secreted glial proliferative factors after pesticide exposure. Neither COX-2 nor CYP450 pharmacological inhibition were able to revert the effect of secretomes on their respective acceptor cells. In contrast, the inhibition of LOX-15, enzyme responsible for the generation of anti-inflammatory lipid mediators, abolished the glial proliferative effect of neuronal secretome during MB toxicity. In addition, the neuroprotective effect of astrocyte-derived secretome was blocked. Next, we evaluated the role of FPR2/ALX receptor, whose main ligands are lipid mediators associated with resolution. The antagonist of FPR2/ALX, Quin-C7, blocked the effect of the astrocytic secretome on neuronal survival upon MB challenge. In agreement, FPR2/ALX activation by a specific agonist enhanced the neuroprotective effect of the astrocytic secretome. To determine the role of FPR2/ALX downstream signaling, cells were incubated with PI3K and ERK1/2 pharmacological inhibitors, After MB exposure, neuronal and astrocytic viability was nondependent of ERK1/2 activation. On the contrary, the blockage of PI3K showed to increase pesticide-induced cell death. Moreover, ERK1/2 phosphorylation was diminished by MB in both cell types. Interestingly, we found that the astrocyte proliferation caused by the secretome derived from MB-exposed neurons was mediated by ERK1/2 activation. Our results suggest that FPR2/ALX signaling and their lipid ligands are involved in the neuronal-glial crosstalk during MB exposure. These findings pay the way for interventions aimed at enhancing the resolution response during pesticide-induced neurotoxicity.
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: 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
Congreso LVIII Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular 2022
Mendoza
Argentina
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Materia
Neuron-astroglia crosstalk
Neurotoxicity
Resolvins
Maneb
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:11336/227485
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/227485
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicityBenzi Juncos, Oriana NicoleAlza, Natalia PaolaSalvador, Gabriela AlejandraNeuron-astroglia crosstalkNeurotoxicityResolvinsManebhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Neurotoxicity generated by several environmental factors has been widely associated with Parkinson’s disease (PD). Human prolonged exposure to the pesticide Maneb (MB) has been reported as a triggering insult for dopaminergic neurodegeneration and the onset of PD. Even though this effect has been well documented in numerous epidemiological and research studies, little is yet known about the mechanisms underlying MB neurotoxicity in neuron-glia crosstalk. Based on our previous reports about the involvement of cyclooxygenases (COX) and lipoxygenases (LOX) in the neuronal response to MB toxicity (SAIB2021), our aim was to elucidate the role of these lipid mediators’ pathways in neuron-glia communication. To study the possible alterations in neuron-glia crosstalk caused by MB exposure, dopaminergic N27 cells were exposed to astrocyte (C6 cell line) secretome and vice versa. Astrocytes’ secretome showed to be neuroprotective against MB, whereas neurons secreted glial proliferative factors after pesticide exposure. Neither COX-2 nor CYP450 pharmacological inhibition were able to revert the effect of secretomes on their respective acceptor cells. In contrast, the inhibition of LOX-15, enzyme responsible for the generation of anti-inflammatory lipid mediators, abolished the glial proliferative effect of neuronal secretome during MB toxicity. In addition, the neuroprotective effect of astrocyte-derived secretome was blocked. Next, we evaluated the role of FPR2/ALX receptor, whose main ligands are lipid mediators associated with resolution. The antagonist of FPR2/ALX, Quin-C7, blocked the effect of the astrocytic secretome on neuronal survival upon MB challenge. In agreement, FPR2/ALX activation by a specific agonist enhanced the neuroprotective effect of the astrocytic secretome. To determine the role of FPR2/ALX downstream signaling, cells were incubated with PI3K and ERK1/2 pharmacological inhibitors, After MB exposure, neuronal and astrocytic viability was nondependent of ERK1/2 activation. On the contrary, the blockage of PI3K showed to increase pesticide-induced cell death. Moreover, ERK1/2 phosphorylation was diminished by MB in both cell types. Interestingly, we found that the astrocyte proliferation caused by the secretome derived from MB-exposed neurons was mediated by ERK1/2 activation. Our results suggest that FPR2/ALX signaling and their lipid ligands are involved in the neuronal-glial crosstalk during MB exposure. These findings pay the way for interventions aimed at enhancing the resolution response during pesticide-induced neurotoxicity.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: 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; ArgentinaCongreso LVIII Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular 2022MendozaArgentinaSociedad Argentina de Investigaciones en Bioquímica y Biología MolecularSociedad Argentina de Investigaciones en Bioquímica y Biología Molecular2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227485FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity; Congreso LVIII Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular 2022; Mendoza; Argentina; 2022; 87-88CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saib.org.ar/archivos/abstracts.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 Técnicas2025-09-03T09:44:29Zoai:ri.conicet.gov.ar:11336/227485instacron: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 09:44:29.426CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
title FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
spellingShingle FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
Benzi Juncos, Oriana Nicole
Neuron-astroglia crosstalk
Neurotoxicity
Resolvins
Maneb
title_short FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
title_full FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
title_fullStr FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
title_full_unstemmed FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
title_sort FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity
dc.creator.none.fl_str_mv Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author Benzi Juncos, Oriana Nicole
author_facet Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author_role author
author2 Alza, Natalia Paola
Salvador, Gabriela Alejandra
author2_role author
author
dc.subject.none.fl_str_mv Neuron-astroglia crosstalk
Neurotoxicity
Resolvins
Maneb
topic Neuron-astroglia crosstalk
Neurotoxicity
Resolvins
Maneb
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Neurotoxicity generated by several environmental factors has been widely associated with Parkinson’s disease (PD). Human prolonged exposure to the pesticide Maneb (MB) has been reported as a triggering insult for dopaminergic neurodegeneration and the onset of PD. Even though this effect has been well documented in numerous epidemiological and research studies, little is yet known about the mechanisms underlying MB neurotoxicity in neuron-glia crosstalk. Based on our previous reports about the involvement of cyclooxygenases (COX) and lipoxygenases (LOX) in the neuronal response to MB toxicity (SAIB2021), our aim was to elucidate the role of these lipid mediators’ pathways in neuron-glia communication. To study the possible alterations in neuron-glia crosstalk caused by MB exposure, dopaminergic N27 cells were exposed to astrocyte (C6 cell line) secretome and vice versa. Astrocytes’ secretome showed to be neuroprotective against MB, whereas neurons secreted glial proliferative factors after pesticide exposure. Neither COX-2 nor CYP450 pharmacological inhibition were able to revert the effect of secretomes on their respective acceptor cells. In contrast, the inhibition of LOX-15, enzyme responsible for the generation of anti-inflammatory lipid mediators, abolished the glial proliferative effect of neuronal secretome during MB toxicity. In addition, the neuroprotective effect of astrocyte-derived secretome was blocked. Next, we evaluated the role of FPR2/ALX receptor, whose main ligands are lipid mediators associated with resolution. The antagonist of FPR2/ALX, Quin-C7, blocked the effect of the astrocytic secretome on neuronal survival upon MB challenge. In agreement, FPR2/ALX activation by a specific agonist enhanced the neuroprotective effect of the astrocytic secretome. To determine the role of FPR2/ALX downstream signaling, cells were incubated with PI3K and ERK1/2 pharmacological inhibitors, After MB exposure, neuronal and astrocytic viability was nondependent of ERK1/2 activation. On the contrary, the blockage of PI3K showed to increase pesticide-induced cell death. Moreover, ERK1/2 phosphorylation was diminished by MB in both cell types. Interestingly, we found that the astrocyte proliferation caused by the secretome derived from MB-exposed neurons was mediated by ERK1/2 activation. Our results suggest that FPR2/ALX signaling and their lipid ligands are involved in the neuronal-glial crosstalk during MB exposure. These findings pay the way for interventions aimed at enhancing the resolution response during pesticide-induced neurotoxicity.
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: 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
Congreso LVIII Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular 2022
Mendoza
Argentina
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
description Neurotoxicity generated by several environmental factors has been widely associated with Parkinson’s disease (PD). Human prolonged exposure to the pesticide Maneb (MB) has been reported as a triggering insult for dopaminergic neurodegeneration and the onset of PD. Even though this effect has been well documented in numerous epidemiological and research studies, little is yet known about the mechanisms underlying MB neurotoxicity in neuron-glia crosstalk. Based on our previous reports about the involvement of cyclooxygenases (COX) and lipoxygenases (LOX) in the neuronal response to MB toxicity (SAIB2021), our aim was to elucidate the role of these lipid mediators’ pathways in neuron-glia communication. To study the possible alterations in neuron-glia crosstalk caused by MB exposure, dopaminergic N27 cells were exposed to astrocyte (C6 cell line) secretome and vice versa. Astrocytes’ secretome showed to be neuroprotective against MB, whereas neurons secreted glial proliferative factors after pesticide exposure. Neither COX-2 nor CYP450 pharmacological inhibition were able to revert the effect of secretomes on their respective acceptor cells. In contrast, the inhibition of LOX-15, enzyme responsible for the generation of anti-inflammatory lipid mediators, abolished the glial proliferative effect of neuronal secretome during MB toxicity. In addition, the neuroprotective effect of astrocyte-derived secretome was blocked. Next, we evaluated the role of FPR2/ALX receptor, whose main ligands are lipid mediators associated with resolution. The antagonist of FPR2/ALX, Quin-C7, blocked the effect of the astrocytic secretome on neuronal survival upon MB challenge. In agreement, FPR2/ALX activation by a specific agonist enhanced the neuroprotective effect of the astrocytic secretome. To determine the role of FPR2/ALX downstream signaling, cells were incubated with PI3K and ERK1/2 pharmacological inhibitors, After MB exposure, neuronal and astrocytic viability was nondependent of ERK1/2 activation. On the contrary, the blockage of PI3K showed to increase pesticide-induced cell death. Moreover, ERK1/2 phosphorylation was diminished by MB in both cell types. Interestingly, we found that the astrocyte proliferation caused by the secretome derived from MB-exposed neurons was mediated by ERK1/2 activation. Our results suggest that FPR2/ALX signaling and their lipid ligands are involved in the neuronal-glial crosstalk during MB exposure. These findings pay the way for interventions aimed at enhancing the resolution response during pesticide-induced neurotoxicity.
publishDate 2022
dc.date.none.fl_str_mv 2022
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info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/227485
FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity; Congreso LVIII Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular 2022; Mendoza; Argentina; 2022; 87-88
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227485
identifier_str_mv FPR2/ALX signaling and their lipid mediator pathways: pleiotropic roles in neurotoxicity; Congreso LVIII Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular 2022; Mendoza; Argentina; 2022; 87-88
CONICET Digital
CONICET
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dc.publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
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