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- Title
The JNK pathway modulates expression and phosphorylation of 4E-BP1 in MIN6 pancreatic β-cells under oxidative stress conditions.
- Authors
Tominaga, Ryu; Yamaguchi, Suguru; Satake, Chihiro; Usui, Masahiro; Tanji, Yasuhiro; Kondo, Keiichi; Katagiri, Hideki; Oka, Yoshitomo; Ishihara, Hisamitsu
- Abstract
Stress-mediated apoptosis may play a crucial role in loss of pancreatic β-cell mass, contributing to the development of diabetes. We have recently identified that translational control involving the translational suppressor eIF4E binding protein-1 (4E-BP1) which is important for β-cell survival under endoplasmic reticulum (ER) stress. The Eif4ebp1 gene, encoding 4E-BP1, is a direct target of a transcription factor activating transcription factor-4 (ATF4), a master regulator of gene expression in stress responses. In the current study, we investigated 4E-BP1 expression in mouse insulinoma line 6 (MIN6) cells treated with arsenite, an inducer of oxidative stress which is another contributor of β-cell loss. We found that arsenite-induced 4E-BP1 expression level was lower than that induced by thapsigargin, an ER stress inducer, although ATF4 was similarly induced by these agents. The ratio of the dephosphorylated form of 4E-BP1, which has the highest activity, to phosphorylated forms was, however, greater in MIN6 cells treated with arsenite as compared to that in thapsigargin-treated cells. Arsenite-induced 4E-BP1 mRNA and protein expressions were augmented by simultaneous treatment with a c-Jun N-terminal kinase (JNK) specific inhibitor, SP600125. The agent also suppressed the level of the dephosphrylated form of 4E-BP1 in arsenite-treated MIN6 cells. Thus, JNK activated by oxidative stress is involved in the modulation of 4E-BP1 expression and phosphorylation in MIN6 cells, which may contribute to fine tuning of translational control under stress conditions. Copyright © 2010 John Wiley & Sons, Ltd.
- Publication
Cell Biochemistry & Function, 2010, Vol 28, Issue 5, p387
- ISSN
0263-6484
- Publication type
Article
- DOI
10.1002/cbf.1667