Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms

© 2020 by the authors.

Detalles Bibliográficos
Autores: Abbruzzese, Giuseppe, Morón-Oset, Javier, Díaz-Castroverde, Sabela, García-Font, Nuria, Roncero, Cesáreo, López-Muñoz, Francisco, Marco-Contelles, José, Oset-Gasque, María Jesús
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/215639
Acceso en línea:http://hdl.handle.net/10261/215639
Access Level:acceso abierto
Palabra clave:Apoptosis
Autophagy
Brain ischemia
Cell signalling
Natural antioxidants
Neuroprotection
Phytoestrogens
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spelling Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling MechanismsAbbruzzese, GiuseppeMorón-Oset, JavierDíaz-Castroverde, SabelaGarcía-Font, NuriaRoncero, CesáreoLópez-Muñoz, FranciscoMarco-Contelles, JoséOset-Gasque, María JesúsApoptosisAutophagyBrain ischemiaCell signallingNatural antioxidantsNeuroprotectionPhytoestrogens© 2020 by the authors.Phytoestrogens can have a neuroprotective effect towards ischemia-reperfusion-induced neuronal damage. However, their mechanism of action has not been well described. In this work, we investigate the type of neuronal cell death induced by oxygen and glucose deprivation (OGD) and resupply (OGDR) and pinpoint some of the signaling mechanisms whereby the neuroprotective effects of phytoestrogens occur in these conditions. First, we found that autophagy initiation affords neuronal protection upon neuronal damage induced by OGD and OGDR. The mammalian target of rapamycin/ribosomal S6 kinase (mTOR/S6K) pathway is blocked in these conditions, and we provide evidence that this is mediated by modulation of both the 5′ AMP-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathways. These are dampened up or down, respectively, under OGDR-induced neuronal damage. In contrast, the MAPK-Erk kinase/extracellular signal-regulated kinase (MEK/ERK) pathway is increased under these conditions. Regarding the pathways affected by phytoestrogens, we show that their protective properties require autophagy initiation, but at later stages, they decrease mitogen-activated protein kinase (MAPK) and AMPK activation and increase mTOR/S6K activation. Collectively, our results put forward a novel mode of action where phytoestrogens play a dual role in the regulation of autophagy by acting as autophagy initiation enhancers when autophagy is a neuroprotective and pro-survival mechanism, and as autophagy initiation inhibitors when autophagy is a pro-death mechanism. Finally, our results support the therapeutic potential of phytoestrogens in brain ischemia by modulating autophagy.This study was funded by the Ministry of Science and Innovation (MICINN, Spain), grants SAF2010-20337 and BFU2017-83292-R, the Institute of Health Carlos III (ISCIII, Spain), grant RD06/0026/0012, and Camilo José Cela University (Madrid, Spain), grant UCJC-2018-04, to M.J.O-G.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Instituto de Salud Carlos IIIUniversidad Camilo José CelaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/215639reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017-83292-RBFU2017-83292-R/AEI/10.13039/501100011033https://doi.org/10.3390/antiox9060545Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2156392026-05-22T06:33:51Z
dc.title.none.fl_str_mv Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
title Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
spellingShingle Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
Abbruzzese, Giuseppe
Apoptosis
Autophagy
Brain ischemia
Cell signalling
Natural antioxidants
Neuroprotection
Phytoestrogens
title_short Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
title_full Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
title_fullStr Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
title_full_unstemmed Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
title_sort Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms
dc.creator.none.fl_str_mv Abbruzzese, Giuseppe
Morón-Oset, Javier
Díaz-Castroverde, Sabela
García-Font, Nuria
Roncero, Cesáreo
López-Muñoz, Francisco
Marco-Contelles, José
Oset-Gasque, María Jesús
author Abbruzzese, Giuseppe
author_facet Abbruzzese, Giuseppe
Morón-Oset, Javier
Díaz-Castroverde, Sabela
García-Font, Nuria
Roncero, Cesáreo
López-Muñoz, Francisco
Marco-Contelles, José
Oset-Gasque, María Jesús
author_role author
author2 Morón-Oset, Javier
Díaz-Castroverde, Sabela
García-Font, Nuria
Roncero, Cesáreo
López-Muñoz, Francisco
Marco-Contelles, José
Oset-Gasque, María Jesús
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Instituto de Salud Carlos III
Universidad Camilo José Cela
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Apoptosis
Autophagy
Brain ischemia
Cell signalling
Natural antioxidants
Neuroprotection
Phytoestrogens
topic Apoptosis
Autophagy
Brain ischemia
Cell signalling
Natural antioxidants
Neuroprotection
Phytoestrogens
description © 2020 by the authors.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/215639
url http://hdl.handle.net/10261/215639
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017-83292-R
BFU2017-83292-R/AEI/10.13039/501100011033
https://doi.org/10.3390/antiox9060545
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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