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PI3K-Akt-mTOR signal inhibition affects expression of genes related to endoplasmic reticulum stress
1Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China.
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 serum-free 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 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-Akt-mTOR signaling pathway might be involved in the down-regulation of the TM-induced ER stress in primary goose hepatocytes.
Insights
The PI3K-Akt-mTOR pathway regulates tunicamycin-induced endoplasmic reticulum (ER) stress in goose hepatocytes. Inhibiting this pathway reduces ER stress markers, suggesting its role in managing ER stress responses.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Biochemistry
Background:
- The PI3K-Akt-mTOR signaling pathway is implicated in cellular processes, including endoplasmic reticulum (ER) stress.
- The precise mechanism by which this pathway influences ER stress remains incompletely understood.
- Investigating this relationship is crucial for understanding cellular responses to stress.
Purpose of the Study:
- To determine if the PI3K-Akt-mTOR pathway regulates tunicamycin (TM)-induced ER stress gene expression in primary goose hepatocytes.
- To elucidate the role of PI3K-Akt-mTOR signaling in managing ER stress.
- To identify potential therapeutic targets for ER stress-related conditions.
Main Methods:
- Primary goose hepatocytes were cultured in vitro.
- Hepatocytes were treated with tunicamycin (TM) alone or with PI3K-Akt-mTOR inhibitors (LY294002, rapamycin, NVP-BEZ235).
- mRNA levels of ER stress genes (BIP, EIF2a, ATF6, XBP1) were quantified using RT-qPCR.
Main Results:
- Tunicamycin significantly upregulated the mRNA levels of ER stress genes BIP, EIF2a, ATF6, and XBP1.
- Treatment with PI3K-Akt-mTOR inhibitors significantly downregulated the TM-induced mRNA expression of these ER stress genes.
- The results demonstrate a clear modulatory effect of the PI3K-Akt-mTOR pathway on ER stress.
Conclusions:
- The PI3K-Akt-mTOR signaling pathway plays a significant role in regulating tunicamycin-induced endoplasmic reticulum stress in primary goose hepatocytes.
- Inhibition of the PI3K-Akt-mTOR pathway attenuates ER stress marker gene expression.
- This pathway is a potential target for interventions aimed at managing ER stress.
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