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dc.contributor.authorOrzáez, Mar-
dc.contributor.authorSancho, Mónica-
dc.contributor.authorMarchán, Sandra-
dc.contributor.authorMondragón, Laura-
dc.contributor.authorMontava, Rebeca-
dc.contributor.authorGarcía Valero, Juan-
dc.contributor.authorLandeta, Olatz-
dc.contributor.authorBasañez, Gorka-
dc.contributor.authorCarbajo, Rodrigo J.-
dc.contributor.authorPineda-Lucena, Antonio-
dc.contributor.authorBujons, Jordi-
dc.contributor.authorMoure, Alejandra-
dc.contributor.authorMesseguer Peypoch, Ángel-
dc.contributor.authorLagunas, Carmen-
dc.contributor.authorHerrero, Carmen-
dc.contributor.authorPérez-Payá, Enrique-
dc.date.accessioned2014-10-29T09:14:26Z-
dc.date.available2014-10-29T09:14:26Z-
dc.date.issued2014-10-20-
dc.identifier.citationPLoS ONE 9(10):e110979. (2014)es_ES
dc.identifier.urihttp://hdl.handle.net/10261/103949-
dc.description11 páginas, 4 figuras.es_ES
dc.description.abstractBACKGROUND: Excessive apoptosis induces unwanted cell death and promotes pathological conditions. Drug discovery efforts aimed at decreasing apoptotic damage initially targeted the inhibition of effector caspases. Although such inhibitors were effective, safety problems led to slow pharmacological development. Therefore, apoptosis inhibition is still considered an unmet medical need. METHODOLOGY AND PRINCIPAL FINDINGS: The interaction between Apaf-1 and the inhibitors was confirmed by NMR. Target specificity was evaluated in cellular models by siRNa based approaches. Cell recovery was confirmed by MTT, clonogenicity and flow cytometry assays. The efficiency of the compounds as antiapoptotic agents was tested in cellular and in vivo models of protection upon cisplatin induced ototoxicity in a zebrafish model and from hypoxia and reperfusion kidney damage in a rat model of hot ischemia. CONCLUSIONS: Apaf-1 inhibitors decreased Cytc release and apoptosome-mediated activation of procaspase-9 preventing cell and tissue damage in ex vivo experiments and in vivo animal models of apoptotic damage. Our results provide evidence that Apaf-1 pharmacological inhibition has therapeutic potential for the treatment of apoptosis-related diseases.es_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministry of Science and Innovation (MICINN - BIO2007-60066, SAF2008-00048, SAF30542-C01-01 and SAF2010-15512), Laboratorios SALVAT, S.A., Fundacio´n Renal Toma´s de Osma, Generalitat Valenciana Prometeo 2010/005 (partially funded with ERDF), Consolider-Ingenio 2010 (MICINN - CSD2008-00005C) and by the Generalitat Valenciana through Prometeo 2014/061. Moure was funded by a predoctoral fellowship from JAE-pre CSIC.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rightsopenAccesses_ES
dc.titleApaf-1 inhibitors protect from unwanted cell death in in vivo models of kidney ischemia and chemotherapy induced ototoxicityes_ES
dc.typeartículoes_ES
dc.identifier.doi10.1371/journal.pone.0110979-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pone.0110979es_ES
dc.identifier.e-issn1932-6203-
dc.relation.csices_ES
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