Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers

Autores
Pascual, Ana Clara; Salas, Sabrina Rosicler; Pasquaré, Susana Juana
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Insulin (Ins) plays an important role in synaptic plasticity and is tightly related to Alzheimer´s disease (AD). Aβ oligomers (AβO), which are responsible for synaptic dysfunction in AD, can bind to Ins receptor (IR) and can therefore be internalized into neurons. AβO also disrupt the synaptic membrane and diminish 2-AG availability, the main neuroprotective cannabinoid. Ins can prevent AβO binding to IR, thus attenuating its neurotoxicity. Here, we hypothesized that Ins prevent AβO deleterious effects on 2-AG metabolism. To this end, we isolated cerebral cortex synaptosomes (syn) by differential centrifugation purified in ficoll gradients and preincubated them with 10 µM LY294002 (phosphatidylinositol-3-kinase -PI3K- inhibitor) or 100 µM genistein (tyrosine kinase inhibitor) for 10 min, and subsequently incubated with 0.2 mM vanadate (protein-tyrosine phosphatase inhibitor), 100 nM Ins, or 0.2 mM vanadate plus 100 nM Ins, for 30 min. Syn were then incubated for 10 min with or without 0.1 µM AβO. After this incubation, activation of IR signaling by Western Blot, released LDH activity, and 2-AG hydrolysis activity were evaluated. It was observed that a 30 min incubation with Ins and vanadate activated IR and Akt (p<0.05). The subsequent incubation with AβO did not alter IR activation (p>0.05). As to syn membrane damage, neither of the pretreatments could prevent AβO effect on LDH release (p>0.05). On the other hand, Ins and vanadate decreased 2-AG hydrolysis (p<0.01) and their effect was not observed if syn were preincubated with LY (p>0.05). However, in the presence of AβO, Ins and vanadate failed to alter 2-AG hydrolysis (p>0.05) and LY increased this activity (p<0.001). Our results show a regulation of 2-AG hydrolysis by Ins, possibly increasing its availability via IR and involving PI3K pathway, which is abolished by AβO. The effect of AβO appears to be independent of IR and to involve PI3K activity. Ins also failed in preventing AβO damage in synaptic membrane.
Fil: Pascual, Ana Clara. 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: Salas, Sabrina Rosicler. 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: Pasquaré, Susana Juana. 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
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
INISULIN
ALZHEIMER'S DISEASE
2-ARACHIDONOYLGLYCEROL
SYNAPTOSOMES
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:11336/153958
Acceder
id CONICETDig_e75fd1fa8c964dc6be1f46dde5797a49
oai_identifier_str oai:ri.conicet.gov.ar:11336/153958
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomersPascual, Ana ClaraSalas, Sabrina RosiclerPasquaré, Susana JuanaINISULINALZHEIMER'S DISEASE2-ARACHIDONOYLGLYCEROLSYNAPTOSOMEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Insulin (Ins) plays an important role in synaptic plasticity and is tightly related to Alzheimer´s disease (AD). Aβ oligomers (AβO), which are responsible for synaptic dysfunction in AD, can bind to Ins receptor (IR) and can therefore be internalized into neurons. AβO also disrupt the synaptic membrane and diminish 2-AG availability, the main neuroprotective cannabinoid. Ins can prevent AβO binding to IR, thus attenuating its neurotoxicity. Here, we hypothesized that Ins prevent AβO deleterious effects on 2-AG metabolism. To this end, we isolated cerebral cortex synaptosomes (syn) by differential centrifugation purified in ficoll gradients and preincubated them with 10 µM LY294002 (phosphatidylinositol-3-kinase -PI3K- inhibitor) or 100 µM genistein (tyrosine kinase inhibitor) for 10 min, and subsequently incubated with 0.2 mM vanadate (protein-tyrosine phosphatase inhibitor), 100 nM Ins, or 0.2 mM vanadate plus 100 nM Ins, for 30 min. Syn were then incubated for 10 min with or without 0.1 µM AβO. After this incubation, activation of IR signaling by Western Blot, released LDH activity, and 2-AG hydrolysis activity were evaluated. It was observed that a 30 min incubation with Ins and vanadate activated IR and Akt (p<0.05). The subsequent incubation with AβO did not alter IR activation (p>0.05). As to syn membrane damage, neither of the pretreatments could prevent AβO effect on LDH release (p>0.05). On the other hand, Ins and vanadate decreased 2-AG hydrolysis (p<0.01) and their effect was not observed if syn were preincubated with LY (p>0.05). However, in the presence of AβO, Ins and vanadate failed to alter 2-AG hydrolysis (p>0.05) and LY increased this activity (p<0.001). Our results show a regulation of 2-AG hydrolysis by Ins, possibly increasing its availability via IR and involving PI3K pathway, which is abolished by AβO. The effect of AβO appears to be independent of IR and to involve PI3K activity. Ins also failed in preventing AβO damage in synaptic membrane.Fil: Pascual, Ana Clara. 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: Salas, Sabrina Rosicler. 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: Pasquaré, Susana Juana. 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; ArgentinaReunión Anual de Sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista MedicinaCostas, Monica Alejandra2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/153958Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 70-700025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:17:02Zoai:ri.conicet.gov.ar:11336/153958instacron: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:34982025-09-10 13:17:02.879CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
title Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
spellingShingle Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
Pascual, Ana Clara
INISULIN
ALZHEIMER'S DISEASE
2-ARACHIDONOYLGLYCEROL
SYNAPTOSOMES
title_short Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
title_full Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
title_fullStr Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
title_full_unstemmed Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
title_sort Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers
dc.creator.none.fl_str_mv Pascual, Ana Clara
Salas, Sabrina Rosicler
Pasquaré, Susana Juana
author Pascual, Ana Clara
author_facet Pascual, Ana Clara
Salas, Sabrina Rosicler
Pasquaré, Susana Juana
author_role author
author2 Salas, Sabrina Rosicler
Pasquaré, Susana Juana
author2_role author
author
dc.contributor.none.fl_str_mv Costas, Monica Alejandra
dc.subject.none.fl_str_mv INISULIN
ALZHEIMER'S DISEASE
2-ARACHIDONOYLGLYCEROL
SYNAPTOSOMES
topic INISULIN
ALZHEIMER'S DISEASE
2-ARACHIDONOYLGLYCEROL
SYNAPTOSOMES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Insulin (Ins) plays an important role in synaptic plasticity and is tightly related to Alzheimer´s disease (AD). Aβ oligomers (AβO), which are responsible for synaptic dysfunction in AD, can bind to Ins receptor (IR) and can therefore be internalized into neurons. AβO also disrupt the synaptic membrane and diminish 2-AG availability, the main neuroprotective cannabinoid. Ins can prevent AβO binding to IR, thus attenuating its neurotoxicity. Here, we hypothesized that Ins prevent AβO deleterious effects on 2-AG metabolism. To this end, we isolated cerebral cortex synaptosomes (syn) by differential centrifugation purified in ficoll gradients and preincubated them with 10 µM LY294002 (phosphatidylinositol-3-kinase -PI3K- inhibitor) or 100 µM genistein (tyrosine kinase inhibitor) for 10 min, and subsequently incubated with 0.2 mM vanadate (protein-tyrosine phosphatase inhibitor), 100 nM Ins, or 0.2 mM vanadate plus 100 nM Ins, for 30 min. Syn were then incubated for 10 min with or without 0.1 µM AβO. After this incubation, activation of IR signaling by Western Blot, released LDH activity, and 2-AG hydrolysis activity were evaluated. It was observed that a 30 min incubation with Ins and vanadate activated IR and Akt (p<0.05). The subsequent incubation with AβO did not alter IR activation (p>0.05). As to syn membrane damage, neither of the pretreatments could prevent AβO effect on LDH release (p>0.05). On the other hand, Ins and vanadate decreased 2-AG hydrolysis (p<0.01) and their effect was not observed if syn were preincubated with LY (p>0.05). However, in the presence of AβO, Ins and vanadate failed to alter 2-AG hydrolysis (p>0.05) and LY increased this activity (p<0.001). Our results show a regulation of 2-AG hydrolysis by Ins, possibly increasing its availability via IR and involving PI3K pathway, which is abolished by AβO. The effect of AβO appears to be independent of IR and to involve PI3K activity. Ins also failed in preventing AβO damage in synaptic membrane.
Fil: Pascual, Ana Clara. 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: Salas, Sabrina Rosicler. 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: Pasquaré, Susana Juana. 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
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Insulin (Ins) plays an important role in synaptic plasticity and is tightly related to Alzheimer´s disease (AD). Aβ oligomers (AβO), which are responsible for synaptic dysfunction in AD, can bind to Ins receptor (IR) and can therefore be internalized into neurons. AβO also disrupt the synaptic membrane and diminish 2-AG availability, the main neuroprotective cannabinoid. Ins can prevent AβO binding to IR, thus attenuating its neurotoxicity. Here, we hypothesized that Ins prevent AβO deleterious effects on 2-AG metabolism. To this end, we isolated cerebral cortex synaptosomes (syn) by differential centrifugation purified in ficoll gradients and preincubated them with 10 µM LY294002 (phosphatidylinositol-3-kinase -PI3K- inhibitor) or 100 µM genistein (tyrosine kinase inhibitor) for 10 min, and subsequently incubated with 0.2 mM vanadate (protein-tyrosine phosphatase inhibitor), 100 nM Ins, or 0.2 mM vanadate plus 100 nM Ins, for 30 min. Syn were then incubated for 10 min with or without 0.1 µM AβO. After this incubation, activation of IR signaling by Western Blot, released LDH activity, and 2-AG hydrolysis activity were evaluated. It was observed that a 30 min incubation with Ins and vanadate activated IR and Akt (p<0.05). The subsequent incubation with AβO did not alter IR activation (p>0.05). As to syn membrane damage, neither of the pretreatments could prevent AβO effect on LDH release (p>0.05). On the other hand, Ins and vanadate decreased 2-AG hydrolysis (p<0.01) and their effect was not observed if syn were preincubated with LY (p>0.05). However, in the presence of AβO, Ins and vanadate failed to alter 2-AG hydrolysis (p>0.05) and LY increased this activity (p<0.001). Our results show a regulation of 2-AG hydrolysis by Ins, possibly increasing its availability via IR and involving PI3K pathway, which is abolished by AβO. The effect of AβO appears to be independent of IR and to involve PI3K activity. Ins also failed in preventing AβO damage in synaptic membrane.
publishDate 2019
dc.date.none.fl_str_mv 2019
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/11336/153958
Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 70-70
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/153958
identifier_str_mv Insulin receptor activation effects on synaptosomal 2-AG hydrolysis in an amyloidosis model induced by AB oligomers; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 70-70
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://www.saic.org.ar/revista-medicina
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
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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