IB1 reduces cytokine-induced apoptosis of insulin-secreting cells.

Details

Serval ID
serval:BIB_E50D7CCD42ED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IB1 reduces cytokine-induced apoptosis of insulin-secreting cells.
Journal
Journal of Biological Chemistry
Author(s)
Bonny C., Oberson A., Steinmann M., Schorderet D.F., Nicod P., Waeber G.
ISSN
0021-9258
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
275
Number
22
Pages
16466-16472
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
IB1/JIP-1 is a scaffold protein that interacts with upstream components of the c-Jun N-terminal kinase (JNK) signaling pathway. IB1 is expressed at high levels in pancreatic beta cells and may therefore exert a tight control on signaling events mediated by JNK in these cells. Activation of JNK by interleukin 1 (IL-1beta) or by the upstream JNK constitutive activator DeltaMEKK1 promoted apoptosis in two pancreatic beta cell lines and decreased IB1 content by 50-60%. To study the functional consequences of the reduced IB1 content in beta cell lines, we used an insulin-secreting cell line expressing an inducible IB1 antisense RNA that lead to a 38% IB1 decrease. Reducing IB1 levels in these cells increased phosphorylation of c-Jun and increased the apoptotic rate in presence of IL-1beta. Nitric oxide production was not stimulated by expression of the IB1 antisense RNA. Complementary experiments indicated that overexpression of IB1 in insulin-producing cells prevented JNK-mediated activation of the transcription factors c-Jun, ATF2, and Elk1 and decreased IL-1beta- and DeltaMEKK1-induced apoptosis. These data indicate that IB1 plays an anti-apoptotic function in insulin-producing cells probably by controlling the activity of the JNK signaling pathway.
Keywords
Apoptosis, Doxycycline, Glucose, Insulin, Interleukin-1, Islets of Langerhans, Nitric Oxide, Nuclear Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, RNA, Antisense, Trans-Activators, Ultraviolet Rays
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:58
Last modification date
20/08/2019 16:08
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