Title: Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance
Authors: Colli, Maikel L
Nogueira, Tatiane C
Allagnat, Florent
Cunha, Daniel A
Gurzov, Esteban N
Cardozo, Alessandra K
Roivainen, Merja
Op De Beeck, Anne
Eizirik, Decio L # ×
Issue Date: Sep-2011
Publisher: Public Library of Science
Series Title: PLoS Pathogens vol:7 issue:9 pages:e1002267
Article number: 10.1371/journal.ppat.1002267
Abstract: The rise in type 1 diabetes (T1D) incidence in recent decades is probably related to modifications in environmental factors. Viruses are among the putative environmental triggers of T1D. The mechanisms regulating beta cell responses to viruses, however, remain to be defined. We have presently clarified the signaling pathways leading to beta cell apoptosis following exposure to the viral mimetic double-stranded RNA (dsRNA) and a diabetogenic enterovirus (Coxsackievirus B5). Internal dsRNA induces cell death via the intrinsic mitochondrial pathway. In this process, activation of the dsRNA-dependent protein kinase (PKR) promotes eIF2α phosphorylation and protein synthesis inhibition, leading to downregulation of the antiapoptotic Bcl-2 protein myeloid cell leukemia sequence 1 (Mcl-1). Mcl-1 decrease results in the release of the BH3-only protein Bim, which activates the mitochondrial pathway of apoptosis. Indeed, Bim knockdown prevented both dsRNA- and Coxsackievirus B5-induced beta cell death, and counteracted the proapoptotic effects of Mcl-1 silencing. These observations indicate that the balance between Mcl-1 and Bim is a key factor regulating beta cell survival during diabetogenic viral infections.
ISSN: 1553-7366
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
PLOS pathogens.pdf Published 1190KbAdobe PDFView/Open


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science