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

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...

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Autores: Abbruzzese, Giuseppe, Morón Oset, Javier, Díaz Castroverde, Sabela, García Font, Nuria, Roncero Romero, Cesáreo, López Muñoz, Francisco, Marco Contelles, José Luis, Oset Gasque, María Jesús
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/8392
Acesso em linha:https://hdl.handle.net/20.500.14352/8392
Access Level:acceso abierto
Palavra-chave:apoptosis
autophagy
brain ischemia
cell signaling
natural antioxidants
neuroprotection
phytoestrogens
Neurociencias (Medicina)
Biología celular (Farmacia)
Bioquímica (Farmacia)
2490 Neurociencias
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network_name_str España
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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 Romero, CesáreoLópez Muñoz, FranciscoMarco Contelles, José LuisOset Gasque, María Jesúsapoptosisautophagybrain ischemiacell signalingnatural antioxidantsneuroprotectionphytoestrogensNeurociencias (Medicina)Biología celular (Farmacia)Bioquímica (Farmacia)2490 NeurocienciasPhytoestrogens 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 50 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.MDPIUniversidad Complutense de Madrid20202020-06-2220202020-06-22journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/8392reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/83922026-06-02T12:44:21Z
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 signaling
natural antioxidants
neuroprotection
phytoestrogens
Neurociencias (Medicina)
Biología celular (Farmacia)
Bioquímica (Farmacia)
2490 Neurociencias
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 Romero, Cesáreo
López Muñoz, Francisco
Marco Contelles, José Luis
Oset Gasque, María Jesús
author Abbruzzese, Giuseppe
author_facet Abbruzzese, Giuseppe
Morón Oset, Javier
Díaz Castroverde, Sabela
García Font, Nuria
Roncero Romero, Cesáreo
López Muñoz, Francisco
Marco Contelles, José Luis
Oset Gasque, María Jesús
author_role author
author2 Morón Oset, Javier
Díaz Castroverde, Sabela
García Font, Nuria
Roncero Romero, Cesáreo
López Muñoz, Francisco
Marco Contelles, José Luis
Oset Gasque, María Jesús
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv apoptosis
autophagy
brain ischemia
cell signaling
natural antioxidants
neuroprotection
phytoestrogens
Neurociencias (Medicina)
Biología celular (Farmacia)
Bioquímica (Farmacia)
2490 Neurociencias
topic apoptosis
autophagy
brain ischemia
cell signaling
natural antioxidants
neuroprotection
phytoestrogens
Neurociencias (Medicina)
Biología celular (Farmacia)
Bioquímica (Farmacia)
2490 Neurociencias
description 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 50 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-06-22
2020
2020-06-22
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/8392
url https://hdl.handle.net/20.500.14352/8392
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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