Journal article
MCL-1 is a key antiapoptotic protein in human and rodent pancreatic β-cells
K Meyerovich, NM Violato, M Fukaya, V Dirix, N Pachera, L Marselli, P Marchetti, A Strasser, DL Eizirik, AK Cardozo
Diabetes | AMER DIABETES ASSOC | Published : 2017
DOI: 10.2337/db16-1252
Abstract
Induction of endoplasmic reticulum stress and activation of the intrinsic apoptotic pathway is widely believed to contribute to β-Cell death in type 1 diabetes (T1D). MCL-1 is an antiapoptotic member of the BCL-2 protein family, whose depletion causes apoptosis in rodent b-cells in vitro. Importantly, decreased MCL-1 expression was observed in islets from patients with T1D. We report here that MCL-1 downregulation is associated with cytokinemediated killing of human b-cells, a process partially prevented by MCL-1 overexpression. By generating a b-cell-specific Mcl-1 knockout mouse strain (bMcl-1KO), we observed that, surprisingly, MCL-1 ablation does not affect islet development and function..
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Awarded by European Federation of Pharmaceutical Industries and Associations
Funding Acknowledgements
N.M.V. was the recipient of a PhD scholarship from the Sao Paulo Research Foundation (2015/01237-0). P.M. and D.L.E. received funding from the European Union's Horizon 2020 research and innovation programme project T2DSystems (667191) and from the Innovative Medicines Initiative 2 joint undertaking (INNODIA) (115797). This joint undertaking receives support from the Union's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations, JDRF, and The Leona M. and Harry B. Helmsley Charitable Trust. The research of the A.S. group was supported by the National Health and Medical Research Council (NHMRC) (1016701) and the Leukemia & Lymphoma Society of America (Specialized Center of Research, 7001-13). A.S. is a recipient of an NHMRC Senior Principal Research Fellow Fellowship (1020363). The research of D.L.E. was supported by the National Funds from Scientific Research (FNRS) (T.0036.13). Work in the A.K.C. group was supported by JDRF (1-2011-589), Actions de Recherche Concertees de la Communaute Francaise (ARC-Belgium, 20063), and FNRS (Belgium, T.0107.16).