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dc.contributor.authorVecino, Rebecaes_ES
dc.contributor.authorBarrio, Emiliaes_ES
dc.contributor.authorSánchez Morán, Irenees_ES
dc.contributor.authorSuarez-Pindado, Albertoes_ES
dc.contributor.authorBolaños, Juan P.es_ES
dc.contributor.authorAlmeida, Angeleses_ES
dc.contributor.authorDelgado-Esteban, Maríaes_ES
dc.date.accessioned2020-10-14T08:51:36Z-
dc.date.available2020-10-14T08:51:36Z-
dc.date.issued2019-
dc.identifier.citation42ⁿᵈ Congress of the Spanish Society of Biochemistry and Molecular Biology (2019)es_ES
dc.identifier.urihttp://hdl.handle.net/10261/221127-
dc.descriptionResumen del trabajo presentado al Spanish Society of Biochemistry and Molecular Biology (SEBBM), celebrado en Madrid del 16 al 19 de julio de 2019.es_ES
dc.description.abstractAttenuation of cell apoptosis has been involved in endogenous neuroprotection induced during brain tolerance related to ischemic preconditioning (IPC). The PI3K/Akt pathway regulates cell development, growth, and survival. Several studies have reported that activated Akt, a serine-threonine specific protein kinase B enhances MDM2-mediated p53 destabilization triggering survival in cancer cells. Recently, we demonstrated that IPC prevents the activation of p53/PUMA/Caspase-3 apoptotic pathway by increasing MDM2/p53 interaction in cortical neurons. Here, we aimed to clarify the role of Akt in the IPC-induced neuronal tolerance against lethal ischemia. To do that, primary cortical neurons were exposed to a validated in vitro model of IPC (oxygen glucose deprivation; OGD; 20 min) prior to prolonged ischemia (OGD, 90min). Akt levels were modulated by specific siRNA and PI3K/Akt activity was inhibited by wortmannin. Protein levels were determined by Western blotting. Neuronal apoptosis (Annexin-V-staining and caspase-3 activation) was analyzed by flow cytometry and fluorimetry. For ectopic human MDM2 expression, a plasmid construction expressing YFP-tagged Mdm2 was used. Our results show that IPC promoted early phosphorylation of Akt, followed by an increase in Akt-MDM2 interaction. Indeed, Akt activation promoted stabilization of phosphorylated MDM2, which enhanced IPC-promoted nuclear MDM2-p53 complex at 4 hours of reoxygenation after ischemia. Furthermore, PI3K/Akt specific inhibition by wortmannin and siRNA against Akt, completely induced a cytosolic MDM2 translocation, leading to the prevention of IPC-mediated neuroprotection. In conclusion, the PI3K/Akt signaling pathway is involved in ischemic tolerance, through controlling the MDM2/p53 interaction.es_ES
dc.description.sponsorshipThe work was funded by The Instituto de Salud Carlos III (PI18/00103 and RD16/0019/0018); FEDER (European regional development fund); and Junta de Castilla y Leon (IES007P17; Escalera de Excelencia CLU-2017-03 Cofinanciado por el P.O. FEDER de Castilla y Leon 14-20).es_ES
dc.language.isoenges_ES
dc.rightsclosedAccesses_ES
dc.titlePreconditioning-induced early Akt activation controls MDM2/p53 interaction and promotes neuronal ischemic tolerancees_ES
dc.typepóster de congresoes_ES
dc.description.peerreviewedPeer reviewedes_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderJunta de Castilla y Leónes_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100014180es_ES
Appears in Collections:(IBFG) Comunicaciones congresos
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