PI3K/Akt Promotes GRP78 Accumulation and Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in HEK293 Cells

Dai, R. Y.; Chen, S. K.; Yan, D. M.; Chen, R.; Liu, Y. P.; Duan, C. Y.; Li, J.; He, T.; Li, Hong

doi:10.14712/fb2010056020037

Folia Biologica > Archive > 2010, Vol. 56 > Issue 2 > PI3K/Akt Promotes GRP78 Accumulation and…

Fol. Biol. 2010, 56, 37-46

https://doi.org/10.14712/fb2010056020037

PI3K/Akt Promotes GRP78 Accumulation and Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in HEK293 Cells

R. Y. Dai^1,2, S. K. Chen³, D. M. Yan¹, R. Chen⁴, Y. P. Liu¹, C. Y. Duan¹, J. Li², T. He², Hong Li^1,2

¹Department of Biochemistry, Luzhou Medical College, Luzhou, Sichuan, P.R. China
²Key Laboratory of Sichuan Colleges and Universities for Human Disease Cell Signalling and Regulation, Luzhou, Sichuan, P.R. China
³Department of Biology, Luzhou Medical College, Luzhou, Sichuan, P.R. China
⁴Department of Public Health, Luzhou Medical College, Luzhou, Sichuan, P.R. China

Received December 2009
Accepted March 2010

The potential pro-survival role of phosphatidylinositol 3-kinase (PI3K)/Akt during endoplasmic reticulum stress has been well-characterized. However, the detailed mechanisms remain largely unknown. Here, we showed that PI3K/Akt inhibition promoted endoplasmic reticulum stress-induced apoptosis in a glucose-regulated protein 78 (GRP78)-dependent manner. During endoplasmic reticulum stress, high levels of Akt phosphorylation were sustained for at least 18 h in HEK293 cells. Importantly, PI3K/Akt enhanced GRP78 accumulation through increasing its stability following endoplasmic reticulum stress. Furthermore, Akt1, but not Akt2 or Akt3, was involved in GRP78 stability regulation. These results suggest that PI3K/Akt inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells, at least in part, by promoting GRP78 protein stability.