000165904 001__ 165904
000165904 005__ 20260116002211.0
000165904 0247_ $$2doi$$a10.1038/cddis.2014.313
000165904 0248_ $$2sideral$$a87605
000165904 037__ $$aART-2014-87605
000165904 041__ $$aeng
000165904 100__ $$0(orcid)0000-0001-7897-9173$$aAguiló, N.$$uUniversidad de Zaragoza
000165904 245__ $$aBim is a crucial regulator of apoptosis induced by Mycobacterium tuberculosis
000165904 260__ $$c2014
000165904 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165904 5203_ $$aMycobacterium tuberculosis, the causative agent of tuberculosis, induces apoptosis in infected macrophages in vitro and in vivo. However, the molecular mechanism controlling this process is not known. In order to study the involvement of the mitochondrial apoptotic pathway in M. tuberculosis-induced apoptosis, we analysed cell death in M. tuberculosis-infected embryonic fibroblasts (MEFs) derived from different knockout mice for genes involved in this route. We found that apoptosis induced by M. tuberculosis is abrogated in the absence of Bak and Bax, caspase 9 or the executioner caspases 3 and 7. Notably, we show that MEF deficient in the BH3-only BCL-2-interacting mediator of cell death (Bim) protein were also resistant to this process. The relevance of these results has been confirmed in the mouse macrophage cell line J774, where cell transfection with siRNA targeting Bim impaired apoptosis induced by virulent mycobacteria. Notably, only infection with a virulent strain, but not with attenuated ESX-1-defective strains, such as Bacillus Calmette-Guerin and live-attenuated M. tuberculosis vaccine strain MTBVAC, induced Bim upregulation and apoptosis, probably implicating virulence factor early secreted antigenic target 6-kDa protein in this process. Our results suggest that Bim upregulation and apoptosis is mediated by the p38MAPK-dependent pathway. Our findings show that Bim is a master regulator of apoptosis induced by M. tuberculosis.
000165904 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000165904 590__ $$a5.014$$b2014
000165904 591__ $$aCELL BIOLOGY$$b49 / 184 = 0.266$$c2014$$dQ2$$eT1
000165904 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000165904 700__ $$0(orcid)0000-0001-7866-2803$$aUranga, S.$$uUniversidad de Zaragoza
000165904 700__ $$0(orcid)0000-0001-8644-120X$$aMarinova, D.$$uUniversidad de Zaragoza
000165904 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000165904 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000165904 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología
000165904 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000165904 7102_ $$11008$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cProy. investigación HQA
000165904 773__ $$g5, 7 (2014), e1343 [10 pp.]$$pCell death dis.$$tCELL DEATH & DISEASE$$x2041-4889
000165904 8564_ $$s2128062$$uhttps://zaguan.unizar.es/record/165904/files/texto_completo.pdf$$yVersión publicada
000165904 8564_ $$s3542098$$uhttps://zaguan.unizar.es/record/165904/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000165904 909CO $$ooai:zaguan.unizar.es:165904$$particulos$$pdriver
000165904 951__ $$a2026-01-15-21:56:15
000165904 980__ $$aARTICLE