PI3K-Akt-mTOR signal inhibition affects expression of genes related to endoplasmic reticulum stress

Abstract

ABSTRACT. PI3K-Akt-mTOR signaling pathway is associated with endoplasmic reticulum (ER) stress. However, it is not clear how this signaling pathway affects the ER stress. The present study aimed to determine whether the PI3K-Akt-mTOR signaling pathway regulates tunicamycin (TM)-induced increases in mRNA levels of genes involved in the ER stress, to help elucidate the mechanism by which this pathway affects the ER stress in primary goose hepatocytes. Primary hepatocytes were isolated from geese and cultured in vitro. After 12 h in a serumfree medium, the hepatocytes were incubated for 24 h in a medium with either no addition (control) or with supplementation of TM or TM together with PI3K-Akt-mTOR signaling pathway inhibitors (LY294002, rapamycin, NVP-BEZ235). Thereafter, the expression levels of genes involved in the ER stress (BIP, EIF2a, ATF6, and XBP1) were assessed. The results indicated that the mRNA level of BIP 2 Q. Song et al. Genetics and Molecular Research 15 (3): gmr.15037868 was up-regulated in 0.2, 2, and 20 µM TM treatment group (P < 0.05), whereas the mRNA levels of EIF2a, ATF6, and XBP1 were up-regulated in the 2 µM TM treatment group (P < 0.05). However, the TM mediated induction of mRNA levels of genes involved in the ER stress (BIP, EIF2a, ATF6, and XBP1) was down-regulated after the treatment with PI3K-Akt-mTOR pathway inhibitors (LY294002, NVP-BEZ235, and rapamycin). Therefore, our results strongly suggest that the PI3K-AktmTOR signaling pathway might be involved in the down-regulation of the TM-induced ER stress in primary goose hepatocytes.

EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress

“…Evidence has demonstrated that AKT activation positively regulates ER stress via PrPC and Akt-MnSOD pathway in mesenchymal stem cells [31]. Also, PI3K-Akt signal inhibition affects expression of genes related to endoplasmic reticulum stress in primary goose hepatocytes [32]. Thus, our finding that AKT knockdown prevents HG-induced protein expression involved in ER stress activation further confirmed the regulation of AKT on ER stress in renal cells.…”

Angiotensin‐converting enzyme 2 inhibits endoplasmic reticulum stress–associated pathway to preserve nonalcoholic fatty liver disease

“…Our previous results revealed that ACE2 downregulation decreased phosphorylation of Akt . As all we known, Akt not only played a pivotal role in glucose and lipid metabolism signalling pathway but also associated with ERS . Evidence showed that suppression of Akt signalling could induce the ERS and subsequent apoptosis .…”

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

“…ERS shares a correlation with the PI3K/Akt/mTOR signaling pathway. Our experimental data revealed that increases in ERS are followed by decreases in PI3K/AKT/mTOR signaling, as well as reductions in chemoresistance; when the PI3K/AKT/mTOR signaling pathway is blocked, autophagy and apoptosis factors are increased, chemotherapy resistance is weakened, and the tumor shrinks [27, 59], which has an important function in autophagy and apoptosis regulation [2, 60, 61]. It has been reported that blocking the PI3K/AKT/mTOR cascade promotes autophagy [62] that inhibiting PI3K/Akt/mTOR signaling promotes cell apoptosis in LC [28], which is consistent with our results.…”