000056085 001__ 56085
000056085 005__ 20170503142842.0
000056085 0247_ $$2doi$$a10.1074/jbc.M114.631564
000056085 0248_ $$2sideral$$a89581
000056085 037__ $$aART-2015-89581
000056085 041__ $$aeng
000056085 100__ $$aCatalán, E.
000056085 245__ $$aMouse cytotoxic T cell-derived granzyme B activates the mitochondrial cell death pathway in a bim-dependent fashion
000056085 260__ $$c2015
000056085 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056085 5203_ $$aCytotoxic T cells (Tc) use perforin and granzyme B (gzmB) to kill virus-infected cells and cancer cells. Recent evidence suggests that human gzmB primarily induces apoptosis via the intrinsic mitochondrial pathway by either cleaving Bid or activating Bim leading to the activation of Bak/Bax and subsequent generation of active caspase-3. In contrast, mouse gzmB is thought to predominantly induce apoptosis by directly processing pro-caspase-3. However, in certain mouse cell types gzmB-mediated apoptosis mainly occurs via the mitochondrial pathway. To investigate whether Bim is involved under the latter conditions, we have now employed ex vivo virus-immune mouse Tc that selectively kill by using perforin and gzmB (gzmB+Tc) as effector cells and wild type as well as Bim- or Bak/Bax-deficient spontaneously (3T9) or virus-(SV40) transformed mouse embryonic fibroblast cells as targets. We show that gzmB+Tc-mediated apoptosis (phosphatidylserine translocation, mitochondrial depolarization, cytochrome c release, and caspase-3 activation) was severely reduced in 3T9 cells lacking either Bim or both Bak and Bax. This outcome was related to the ability of Tc cells to induce the degradation of Mcl-1 and Bcl-XL, the anti-apoptotic counterparts of Bim. In contrast, gzmB+Tc-mediated apoptosis was not affected in SV40-transformed mouse embryonic fibroblast cells lacking Bak/Bax. The data provide evidence that Bim participates in mouse gzmB+Tc-mediated apoptosis of certain targets by activating the mitochondrial pathway and suggest that the mode of cell death depends on the target cell. Our results suggest that the various molecular events leading to transformation and/or immortalization of cells have an impact on their relative resistance to the multiple gzmB+Tc-induced death pathways.
000056085 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2008-02139$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2011-25390
000056085 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056085 590__ $$a4.258$$b2015
000056085 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b71 / 289 = 0.246$$c2015$$dQ1$$eT1
000056085 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056085 700__ $$0(orcid)0000-0002-8731-4269$$aJaime-Sánchez, P.$$uUniversidad de Zaragoza
000056085 700__ $$0(orcid)0000-0001-7897-9173$$aAguilo, N.$$uUniversidad de Zaragoza
000056085 700__ $$aSimon, M.M.
000056085 700__ $$aFroelich, C.J.
000056085 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000056085 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDepartamento de Microbiología, Medicina Preventiva y Salud Pública$$cInmunología
000056085 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDepartamento de Bioquímica y Biología Molecular y Celular$$cBioquímica y Biología Molecular
000056085 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDepartamento de Microbiología, Medicina Preventiva y Salud Pública$$cMicrobiología
000056085 773__ $$g290, 11 (2015), 6868-6877$$pJ. biol. chem.$$tJOURNAL OF BIOLOGICAL CHEMISTRY$$x0021-9258
000056085 8564_ $$s640669$$uhttp://zaguan.unizar.es/record/56085/files/texto_completo.pdf$$yVersión publicada
000056085 8564_ $$s140578$$uhttp://zaguan.unizar.es/record/56085/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056085 909CO $$ooai:zaguan.unizar.es:56085$$particulos$$pdriver
000056085 951__ $$a2017-05-03-14:22:37
000056085 980__ $$aARTICLE