PI3K-Akt inactivation induced CHOP expression in endoplasmic reticulum-stressed cells

Hyoda Kanae

Hosoi Toru

Horie Naohiro

Okuma Yasunobu

Ozawa Koichiro

Nomura Yasuyuki

Biochemical and Biophysical Research Communications

Stress signals that impair the function of the endoplasmic reticulum (ER) can lead to an accumulation of unfolded proteins in the ER causing cell death. Recent studies have indicated that ER stress contributes to several diseases such as neurodegenerative disorders or diabetes. In the present study, we found that Akt down-regulation is important for inducing CHOP expression, an ER stress-induced transcription factor. Treatment with tunicamycin or thapsigargin, ER stress inducers, caused dephosphorylation of Akt from 12 to 24 h and induced cell death. Interestingly, treatment with a PI3K inhibitor alone induced CHOP expression and caused cell death. However, a MEK 1 inhibitor induced neither CHOP expression nor cell death. These results indicate that the inactivation of Akt by ER stress induces CHOP expression and causes cell death. Therefore, Akt plays an important role in ER stressed condition and may have important implications for understanding ER stress-related diseases.

endoplasmic reticulum stress

P13K-Akt pathway

LY294002

Wortmannin

PD98059

CHOP

Medical sciences [ 490 ]

eng

Elsevier Inc.

Copyright (c) 2006 Elsevier Inc.

[NCID] AA00564395

[ISSN] 0006-291X

[DOI] 10.1016/j.bbrc.2005.12.007

[DOI] http://dx.doi.org/10.1016/j.bbrc.2005.12.007 isVersionOf