000069706 001__ 69706
000069706 005__ 20190709135610.0
000069706 0247_ $$2doi$$a10.1038/cddis.2017.112
000069706 0248_ $$2sideral$$a104723
000069706 037__ $$aART-2017-104723
000069706 041__ $$aeng
000069706 100__ $$aJakob, A.
000069706 245__ $$aImmunoproteomic identification and characterization of Ni2+-regulated proteins implicates Ni2+ in the induction of monocyte cell death
000069706 260__ $$c2017
000069706 5060_ $$aAccess copy available to the general public$$fUnrestricted
000069706 5203_ $$aNickel allergy is the most common cause of allergic reactions worldwide, with cutaneous and systemic effects potentially affecting multiple organs. Monocytes are precursors of not only macrophages but also dendritic cells, the most potent activators of nickel hypersensitivity. Monocytes are themselves important antigen-presenting cells, capable of nickel-specific T-cell activation in vivo and in vitro, in addition to being important for immediate innate immune inflammation. To elucidate early Ni2+-dependent inflammatory molecular mechanisms in human monocytes, a Ni2+-specific proteomic approach was applied. Quantitative two-dimensional (2D) differential gel electrophoresis and Delta2D software analyses coupled with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) revealed that Ni2+ significantly regulated 56 protein species, of which 36 were analyzed by MALDI-MS. Bioinformatics analyses of all identified proteins resulted in Ni2+-associated functional annotation clusters, such as cell death, metal ion binding, and cytoskeletal remodeling. The involvement of Ni2+ in the induction of monocyte cell death, but not T-cell death, was observed at Ni2+ concentrations at or above 250 µM. Examination of caspase activity during Ni2+-mediated cell death revealed monocytic cell death independent of caspase-3 and -7 activity. However, confocal microscopy analysis demonstrated Ni2+-triggered cytoskeletal remodeling and nuclear condensation, characteristic of cellular apoptosis. Thus, Ni2+-specific peripheral blood mononuclear cell stimulation suggests monocytic cell death at Ni2+ concentrations at or above 250 µM, and monocytic effects on immune regulation at lower Ni2+ concentrations.
000069706 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R$$9info:eu-repo/grantAgreement/EUR/Sens-it-iv/LSHB-CT-2005-018681
000069706 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000069706 590__ $$a5.638$$b2017
000069706 591__ $$aCELL BIOLOGY$$b41 / 190 = 0.216$$c2017$$dQ1$$eT1
000069706 592__ $$a2.536$$b2017
000069706 593__ $$aCancer Research$$c2017$$dQ1
000069706 593__ $$aCell Biology$$c2017$$dQ1
000069706 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000069706 593__ $$aImmunology$$c2017$$dQ1
000069706 593__ $$aCellular and Molecular Neuroscience$$c2017$$dQ1
000069706 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000069706 700__ $$aMussotter, F.
000069706 700__ $$aOhnesorge, S.
000069706 700__ $$aDietz, L.
000069706 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000069706 700__ $$aHaidl, I.D.
000069706 700__ $$aThierse, H.J.
000069706 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000069706 773__ $$g8, 3 (2017), e2684 [12 pp]$$pCell death dis.$$tCell death & disease$$x2041-4889
000069706 8564_ $$s857696$$uhttps://zaguan.unizar.es/record/69706/files/texto_completo.pdf$$yVersión publicada
000069706 8564_ $$s138088$$uhttps://zaguan.unizar.es/record/69706/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000069706 909CO $$ooai:zaguan.unizar.es:69706$$particulos$$pdriver
000069706 951__ $$a2019-07-09-12:21:58
000069706 980__ $$aARTICLE