English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/103949
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

Apaf-1 inhibitors protect from unwanted cell death in in vivo models of kidney ischemia and chemotherapy induced ototoxicity

AuthorsOrzáez, Mar; Sancho, Mónica; Marchán, Sandra; Mondragón, Laura; Montava, Rebeca; García Valero, Juan; Landeta, Olatz; Basañez, Gorka; Carbajo, Rodrigo J.; Pineda-Lucena, Antonio; Bujons, Jordi; Moure, Alejandra; Messeguer Peypoch, Ángel ; Lagunas, Carmen; Herrero, Carmen ; Pérez-Payá, Enrique
Issue Date20-Oct-2014
PublisherPublic Library of Science
CitationPLoS ONE 9(10):e110979. (2014)
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.
Description11 páginas, 4 figuras.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0110979
URIhttp://hdl.handle.net/10261/103949
DOI10.1371/journal.pone.0110979
E-ISSN1932-6203
Appears in Collections:(IBV) Artículos
Files in This Item:
File Description SizeFormat 
Plos One 009-e1-10979.pdf2,88 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.