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

Q Song1, C C Han2, X P Xiong1

  • 1Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China.

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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