PI3K/Akt promotes GRP78 accumulation and inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells.
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.
Dai
R Y
RY
Department of Biochemistry, Luzhou Medical College, Luzhou, Sichuan, P.R. China.
Chen
S K
SK
Yan
D M
DM
Chen
R
R
Lui
Y P
YP
Duan
C Y
CY
Li
J
J
He
T
T
Li
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004229:Dithiothreitol / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism
D004229:Dithiothreitol; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019284:Thapsigargin; D051742:Transcription Factor CHOP; C497249:DDIT3 protein, human; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse