title: PI3K-Akt inactivation induced CHOP expression in endoplasmic reticulum-stressed cells.
abstract: 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 MEK1 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.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Hyoda
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Horie
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okuma
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism*
chemical_list: D051742:Transcription Factor CHOP; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt