Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_062C5C1A6E9B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance.
Périodique
PLoS pathogens
Auteur(s)
Colli M.L., Nogueira T.C., Allagnat F., Cunha D.A., Gurzov E.N., Cardozo A.K., Roivainen M., Op de Beeck A., Eizirik D.L.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
09/2011
Peer-reviewed
Oui
Volume
7
Numéro
9
Pages
e1002267
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Animals, Apoptosis, Apoptosis Regulatory Proteins/metabolism, Bcl-2-Like Protein 11, Cell Line, Cell Survival, Coxsackievirus Infections/metabolism, Coxsackievirus Infections/pathology, Diabetes Mellitus, Type 1/etiology, Diabetes Mellitus, Type 1/metabolism, Diabetes Mellitus, Type 1/pathology, Diabetes Mellitus, Type 1/virology, Enterovirus B, Human/metabolism, Eukaryotic Initiation Factor-2/metabolism, Humans, Insulin-Secreting Cells/metabolism, Insulin-Secreting Cells/pathology, Insulin-Secreting Cells/virology, Male, Membrane Proteins/metabolism, Mitochondria/metabolism, Myeloid Cell Leukemia Sequence 1 Protein, Phosphorylation, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-bcl-2/metabolism, RNA, Double-Stranded/metabolism, RNA, Viral/metabolism, Rats, Rats, Wistar
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/05/2019 9:03
Dernière modification de la notice
20/08/2019 12:28
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