Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12104/41812
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dc.contributor.authorDe La Torre, A.V.-
dc.contributor.authorJunyent, F.-
dc.contributor.authorFolch, J.-
dc.contributor.authorPelegri, C.-
dc.contributor.authorVilaplana, J.-
dc.contributor.authorAuladell, C.-
dc.contributor.authorBeas-Zárate, Carlos-
dc.contributor.authorPallas, M.-
dc.contributor.authorVerdaguer, E.-
dc.contributor.authorCamins, A.-
dc.date.accessioned2015-09-15T18:04:21Z-
dc.date.available2015-09-15T18:04:21Z-
dc.date.issued2012-
dc.identifier.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-84855983255&partnerID=40&md5=edf9579009fb6673266692d4bb10209b-
dc.identifier.urihttp://hdl.handle.net/20.500.12104/41812-
dc.description.abstractIn the present study, we evaluated the effects of roscovitine (Rosco) and flavopiridol (Flavo), both of which are classified as cyclin-dependent kinase (CDK) inhibitors, on apoptosis induced by the inhibition of PI3K/AKT pathway in cerebellar granule neurons (CGNs). Our results demonstrate that both CDK inhibitors prevented apoptosis induced by LY294002 (LY), as also occurs with SB415286 (SB4), a selective GSK3? inhibitor. Our findings also indicate that these CDK inhibitors inhibit GSK3?, representing a potential pharmacological mechanism involved in their neuroprotective properties. Thus, the increased activity of GSK3? induced by LY294002 and detected by dephosphorylation at Ser9 was prevented by both compounds. Likewise, GSK3? activity was measured by a radioactivity assay, revealing that CDK inhibitors and SB415286 prevented the increase in GSK3? activity induced by PI3K inhibition. In addition, we analysed c-Jun, which is also a mediator of PI3K inhibition-induced apoptosis. However, neither of the CDK inhibitors nor SB415286 prevented the increase in c-Jun phosphorylation induced by PI3K inhibition. Therefore, our data identify GSK3? as a crucial mediator of CGN apoptosis induced by PI3K inhibition and indicate that the antiapoptotic effects of CDKs are mediated by the inhibition of this pharmacological target. © 2011 Elsevier Ltd. All rights reserved.-
dc.relation.isreferencedbyScopus-
dc.relation.isreferencedbyWOS-
dc.titleGSK3? inhibition is involved in the neuroprotective effects of cyclin-dependent kinase inhibitors in neurons-
dc.typeArticle-
dc.identifier.doi10.1016/j.phrs.2011.08.006-
dc.relation.ispartofjournalPharmacological Research-
dc.relation.ispartofvolume65-
dc.relation.ispartofissue1-
dc.relation.ispartofpage66-
dc.relation.ispartofpage73-
dc.subject.keywordApoptosis; Cerebellar granular cells; Flavopiridol; GSK3?; Roscovitine-
dc.contributor.affiliationDe La Torre, A.V., Unitat de Farmacologia i Farmacognsia, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain; Junyent, F., Unitat de Farmacologia i Farmacognsia, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain, Unitat de Bioquimica, Facultat de Medicina i Cincies de la Salut, Universitat Rovira i Virgili, C./St. Lloren 21, 43201 Reus (Tarragona), Spain; Folch, J., Unitat de Bioquimica, Facultat de Medicina i Cincies de la Salut, Universitat Rovira i Virgili, C./St. Lloren 21, 43201 Reus (Tarragona), Spain; Pelegrí, C., Departament de Fisiologia, Centro de Investigación de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain; Vilaplana, J., Departament de Fisiologia, Centro de Investigación de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain; Auladell, C., Departament de Biologia Celelular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Beas-Zarate, C., Departamento de Biología Celular y Molecular, Universidad de Guadalajara and División de Neurociencias, Instituto Mexicano Del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, Guadalajara, Jalisco 44340, Mexico; Pallàs, M., Unitat de Farmacologia i Farmacognsia, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain; Verdaguer, E., Departament de Biologia Celelular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Camins, A., Unitat de Farmacologia i Farmacognsia, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain-
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