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dc.contributor.authorDelgado Esteban, Maríaes_ES
dc.contributor.authorMartín Zanca, Dionisioes_ES
dc.contributor.authorAndrés Martín, Lauraes_ES
dc.contributor.authorAlmeida Parra, Ángeleses_ES
dc.contributor.authorBolaños Hernández, Juan Pedro es_ES
dc.date.accessioned2009-01-20es_ES
dc.date.accessioned2009-10-07T09:10:29Z
dc.date.available2009-10-07T09:10:29Z
dc.date.issued2007es_ES
dc.identifier.citationDelgado Esteban, M., Martín Zanca, D., Andrés Martín, L., Almeida Parra, A., y Bolaños Hernández, J.P. (2007). Inhibition of PTEN by peroxynitrite activates the phosphoinositide-3-kinase/Akt neuroprotective signaling pathway. "Journal of Neurochemistry", 102, 194-205.es_ES
dc.identifier.urihttp://hdl.handle.net/10366/17715es_ES
dc.identifier.urihttp://hdl.handle.net/10366/17715
dc.description.abstractEl derivado del óxido nítrico, peroxinitrito, activa una cascada de señalización de supervivencia en neuronas. El mecanismo implica la oxidación de la fosfatasa PTEN, que permite incrementar la forma fosforilada (neuroprotectora) de akt.es_ES
dc.description.abstractPeroxynitrite is usually considered as a neurotoxic nitric oxidederivative. However, an increasing body of evidence suggests that, at low concentrations, peroxynitrite affords transient cytoprotection, both in vitro and in vivo. Here, we addressed the signaling mechanism responsible for this effect, and found that rat cortical neurons in primary culture acutely exposed to peroxynitrite (0.1 mmol/L) rapidly elicited Akt-Ser473 phosphorylation. Inhibition of phosphoinositide-3-kinase (PI3K)/Akt pathway with wortmannin or Akt small hairpin RNA (shRNA) abolished the ability of peroxynitrite to prevent etoposide-induced apoptotic death. Endogenous peroxynitrite formation by short-term incubation of neurons with glutamate stimulated Akt-Ser473 phosphorylation, whereas Akt shRNA enhanced the vulnerability of neurons against glutamate. We further show that Akt-Ser473 phosphorylation was consequence of the oxidizing, but not the nitrating properties of peroxynitrite. Peroxynitrite failed to nitrate or phosphorylate neurotrophin tyrosine kinase receptors (Trks), and it did not modify the ability of brain-derived neurotrophic factor (BDNF), to phosphorylate its cognate receptor, TrkB; however, peroxynitrite enhanced BDNF-mediated Akt-Ser473 phosphorylation. Finally, we found that peroxynitrite-stimulated Akt-Ser473 phosphorylation was associated with an increased proportion of oxidized phosphoinositide phosphatase, PTEN, in neurons. Moreover, peroxynitrite prevented the increase of apoptotic neuronal death caused by over-expression of PTEN. Thus, peroxynitrite exerts neuroprotection by inhibiting PTEN, hence activating the anti-apoptotic PI3K/Akt pathway in primary neurons.es_ES
dc.format.extent12 p.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.languageIngléses_ES
dc.language.isoenges_ES
dc.publisherBlackwell Publishing Ltd. (Oxford, Gran Bretaña)es_ES
dc.relation.requiresAdobe Acrobates_ES
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Unported
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subjectNeuroprotecciónes_ES
dc.subjectAktes_ES
dc.subjectPTENes_ES
dc.subjectApoptosises_ES
dc.subjectÓxido nítricoes_ES
dc.subjectPeroxinitritoes_ES
dc.subjectAnti-apoptotices_ES
dc.subjectNeuroprotectiones_ES
dc.subjectPeroxynitritees_ES
dc.subjectPI3Kes_ES
dc.titleInhibition of PTEN by peroxynitrite activates the phosphoinositide-3-kinase/Akt neuroprotective signaling pathwayes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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