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dc.contributor.author | Ramos Araque, María Esther | |
dc.contributor.author | Rodríguez González, Cristina | |
dc.contributor.author | Vecino Pérez, Rebeca | |
dc.contributor.author | Cortijo Garcia, Elisa | |
dc.contributor.author | de Lera Alfonso, Mercedes | |
dc.contributor.author | Sánchez Barba, Mercedes | |
dc.contributor.author | Colàs-Campàs, Laura | |
dc.contributor.author | Purroy, Francisco | |
dc.contributor.author | Arenillas, Juan F | |
dc.contributor.author | Almeida Parra, María Ángeles | |
dc.contributor.author | Delgado Esteban, María | |
dc.date.accessioned | 2024-02-05T10:39:25Z | |
dc.date.available | 2024-02-05T10:39:25Z | |
dc.date.issued | 2019-04 | |
dc.identifier.citation | https://doi.org/10.1007/s12975-018-0631-1 | es_ES |
dc.identifier.issn | 1868-4483 | |
dc.identifier.uri | http://hdl.handle.net/10366/155312 | |
dc.description.abstract | [EN]Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance. | es_ES |
dc.language.iso | eng | es_ES |
dc.subject | Ischemic Preconditioning | es_ES |
dc.subject | Neurons | es_ES |
dc.subject.mesh | Aged | * |
dc.subject.mesh | Brain Ischemia | * |
dc.subject.mesh | Ischemic Preconditioning | * |
dc.subject.mesh | Glucose | * |
dc.subject.mesh | Excitatory Amino Acid Agonists | * |
dc.subject.mesh | Microtubule-Associated Proteins | * |
dc.subject.mesh | Arginine | * |
dc.subject.mesh | Electron Transport Complex IV | * |
dc.subject.mesh | Humans | * |
dc.subject.mesh | Cells | * |
dc.subject.mesh | Middle Aged | * |
dc.subject.mesh | Cerebral Cortex | * |
dc.subject.mesh | Membrane Potentials | * |
dc.subject.mesh | Subcellular Fractions | * |
dc.subject.mesh | Neurons | * |
dc.subject.mesh | Apoptosis | * |
dc.subject.mesh | Animals | * |
dc.subject.mesh | Caspase 3 | * |
dc.subject.mesh | Tumor Suppressor Protein p53 | * |
dc.subject.mesh | Proline | * |
dc.subject.mesh | Cohort Studies | * |
dc.subject.mesh | Cell Hypoxia | * |
dc.subject.mesh | Mice | * |
dc.subject.mesh | N-Methylaspartate | * |
dc.title | The neuronal ischemic tolerance Is conditioned by the Tp53 Arg72Pro polymorphism | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publishversion | https://doi.org/10.1007/s12975-018-0631-1 | es_ES |
dc.identifier.doi | 10.1007/s12975-018-0631-1 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.pmid | 29687302 | |
dc.identifier.essn | 1868-601X | |
dc.journal.title | Translational Stroke Research | es_ES |
dc.volume.number | 10 | es_ES |
dc.issue.number | 2 | es_ES |
dc.page.initial | 204 | es_ES |
dc.page.final | 215 | es_ES |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es_ES |
dc.subject.decs | proteínas asociadas a microtúbulos | * |
dc.subject.decs | prolina | * |
dc.subject.decs | apoptosis | * |
dc.subject.decs | humanos | * |
dc.subject.decs | ratones | * |
dc.subject.decs | anciano | * |
dc.subject.decs | neuronas | * |
dc.subject.decs | mediana edad | * |
dc.subject.decs | glucosa | * |
dc.subject.decs | hipoxia celular | * |
dc.subject.decs | N-metilaspartato | * |
dc.subject.decs | agonistas de aminoácidos excitadores | * |
dc.subject.decs | proteína supresora de tumor p53 | * |
dc.subject.decs | corteza cerebral | * |
dc.subject.decs | células | * |
dc.subject.decs | animales | * |
dc.subject.decs | estudios de cohortes | * |
dc.subject.decs | arginina | * |
dc.subject.decs | caspasa 3 | * |
dc.subject.decs | isquemia cerebral | * |
dc.subject.decs | complejo IV de transporte de electrones | * |
dc.subject.decs | potenciales de membrana | * |
dc.subject.decs | fracciones subcelulares | * |
dc.subject.decs | preacondicionamiento isquémico | * |
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