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http://hdl.handle.net/10261/61158
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Gómez-Benito, Maria | - |
dc.contributor.author | Carvajal-Vergara, Xonia | - |
dc.contributor.author | Pandiella, Atanasio | - |
dc.date.accessioned | 2012-11-26T12:11:13Z | - |
dc.date.available | 2012-11-26T12:11:13Z | - |
dc.date.issued | 2007 | - |
dc.identifier | doi: 10.1016/j.cellsig.2006.10.009 | - |
dc.identifier | issn: 0898-6568 | - |
dc.identifier.citation | Cellular Signalling 19(4): 844-854 (2007) | - |
dc.identifier.uri | http://hdl.handle.net/10261/61158 | - |
dc.description.abstract | Interferon-α (IFN-α) has been used for the last 20 years in the maintenance therapy of multiple myeloma (MM), though it is only effective in some patients. Congruent with this, IFN-α induces apoptosis in some MM cell lines. Understanding the mechanism of IFN-α-induced apoptosis could be useful in establishing criteria of eligibility for therapy. Here we show that IFN-α-induced apoptosis in the MM cell lines U266 and H929 was completely blocked by a specific inhibitor of Jak1. The mTOR inhibitor rapamycin mitigated apoptosis in U266 but potentiated it in H929 cells. IFN-α induced PS exposure, ΔΨm loss and pro-apoptotic conformational changes of Bak, but not of Bax, and was fully prevented by Mcl-1 overexpression in U266 cells. IFN-α treatment caused the release of cytochrome c from mitochondria to cytosol and consequently, a limited proteolytic processing of caspases. Apoptosis induced by IFN-α was only slightly prevented by caspase inhibitors. Levels of the BH3-only proteins PUMA and Bim increased during IFN-α treatment. Bim increase and apoptosis was prevented by transfection with the siRNA for Bim. PUMA-siRNA transfection reduced electroporation-induced apoptosis but had no effect on apoptosis triggered by IFN-α. The potentiating effect of rapamycin on apoptosis in H929 cells was associated to an increase in basal and IFN-α-induced Bim levels. Our results indicate that IFN-α causes apoptosis in myeloma cells through a moderate triggering of the mitochondrial route initiated by Bim and that mTOR inhibitors may be useful in IFN-α maintenance therapy of certain MM patients. | - |
dc.description.sponsorship | This work was supported by Myeloma Thematic Network grant G03/136 from Fondo de Investigaciones Sanitarias (Ministerio de Sanidad, Spain). | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier | - |
dc.rights | closedAccess | - |
dc.title | Mechanism of apoptosis induced by IFN-α in human myeloma cells: Role of Jak1 and Bim and potentiation by rapamycin | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1016/j.cellsig.2006.10.009 | - |
dc.date.updated | 2012-11-26T12:11:13Z | - |
dc.description.version | Peer Reviewed | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.languageiso639-1 | en | - |
Aparece en las colecciones: | (IBMCC) Artículos |
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accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
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