Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta cells.

Details

Serval ID
serval:BIB_A437670219D3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta cells.
Journal
Molecular Endocrinology
Author(s)
Pétremand J., Bulat N., Butty A.C., Poussin C., Rütti S., Au K., Ghosh S., Mooser V., Thorens B., Yang J.Y., Widmann C., Waeber G.
ISSN
1944-9917[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
23
Number
10
Pages
1572-1586
Language
english
Abstract
High-density lipoproteins (HDLs) protect pancreatic beta cells against apoptosis. This property might relate to the increased risk to develop diabetes in patients with low HDL blood levels. The mechanisms by which HDLs protect beta cells are poorly characterized however. Here we used a transcriptomic approach to identify genes differentially modulated by HDLs in beta cells subjected to apoptotic stimuli. The transcript encoding 4E-BP1 was up-regulated by serum starvation and HDLs blocked this increase. 4E-BP1 inhibits cap-dependent translation in its non- or hypo-phosphorylated state but it looses this ability when hyper-phosphorylated. At the protein level, 4E-BP1 was also up-regulated in response to starvation and IL1beta and this was blunted by HDLs. While an ectopic increase of 4E-BP1 expression induced beta cell death, silencing 4E-BP1 increase with shRNAs inhibited the apoptotic-inducing capacities of starvation. HDLs can therefore protect beta cells by blocking 4E-BP1 protein expression but this is not the sole protective mechanism activated by HDLs. Indeed, HDLs blocked apoptosis induced by ER stress with no associated decrease in total 4E-BP1 induction. Although, HDLs favored the phosphorylation, and hence the inactivation of 4E-BP1 in these conditions, this appeared not to be required for HDL protection. Our results indicate that HDLs can protect beta cells through modulation of 4E-BP1 depending on the type of stress stimuli.
Pubmed
Web of science
Open Access
Yes
Create date
28/07/2009 14:03
Last modification date
20/08/2019 15:09
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