TY - JOUR
T1 - The JNK pathway modulates expression and phosphorylation of 4E-BP1 in MIN6 pancreatic b-cells under oxidative stress conditions
AU - Tominaga, Ryu
AU - Yamaguchi, Suguru
AU - Satake, Chihiro
AU - Usui, Masahiro
AU - Tanji, Yasuhiro
AU - Kondo, Keiichi
AU - Katagiri, Hideki
AU - Oka, Yoshitomo
AU - Ishihara, Hisamitsu
PY - 2010/7
Y1 - 2010/7
N2 - 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 βcell 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 4EBP1 expression in mouse insulinoma line 6 (MIN6) cells treated with arsenite, an inducer of oxidative stress which is another contributor of βcell 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. Arseniteinduced 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.
AB - 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 βcell 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 4EBP1 expression in mouse insulinoma line 6 (MIN6) cells treated with arsenite, an inducer of oxidative stress which is another contributor of βcell 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. Arseniteinduced 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.
KW - 4E-BP1
KW - ER stress
KW - JNK
KW - Oxidative stress
KW - Pancreatic b-cells
UR - http://www.scopus.com/inward/record.url?scp=77956849854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956849854&partnerID=8YFLogxK
U2 - 10.1002/cbf.1667
DO - 10.1002/cbf.1667
M3 - Article
C2 - 20589738
AN - SCOPUS:77956849854
VL - 28
SP - 387
EP - 393
JO - Cell Biochemistry and Function
JF - Cell Biochemistry and Function
SN - 0263-6484
IS - 5
ER -