English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/215639
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

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

AuthorsAbbruzzese, Giuseppe; Morón-Oset, Javier; Díaz-Castroverde, Sabela; García-Font, Nuria; Roncero, Cesáreo; López-Muñoz, Francisco; Marco-Contelles, José ; Oset-Gasque, M. J.
KeywordsApoptosis
Autophagy
Brain ischemia
Cell signaling
Natural antioxidants
Neuroprotection
Phytoestrogens
Issue Date2020
PublisherMultidisciplinary Digital Publishing Institute
CitationAntioxidants 9(6): 545 (2020)
AbstractPhytoestrogens 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.
Description© 2020 by the authors.
Publisher version (URL)https://doi.org/10.3390/antiox9060545
URIhttp://hdl.handle.net/10261/215639
DOIhttp://dx.doi.org/10.3390/antiox9060545
E-ISSN2076-3921
Appears in Collections:(IQOG) Artículos
Files in This Item:
File Description SizeFormat 
Neuroprotection_Abbruzzese_Art2020.pdf1,85 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.