Helicobacter pylori promotes eukaryotic protein translation by activating phosphatidylinositol 3 kinase/mTOR

Area of Science:

• Cellular and Molecular Biology
• Immunology
• Gastroenterology

Background:

• Helicobacter pylori infection triggers innate immune responses in the gastric mucosa.
• Cellular signaling pathways, including those regulating metabolism, are involved in H. pylori pathogenesis.
• The PI3K/Akt/mTOR pathway is crucial for regulating cellular growth, proliferation, and protein synthesis.

Purpose of the Study:

• To investigate the role of the PI3K/Akt/mTOR signaling pathway in H. pylori-induced metabolic regulation and protein synthesis.
• To determine the impact of H. pylori infection on key components of the PI3K/Akt/mTOR pathway and translation machinery.

Main Methods:

• Immunohistochemical analysis of gastric biopsies from patients with gastritis, adenoma, and adenocarcinoma.
• Infection of AGS cells with H. pylori and analysis of signaling pathway activation (e.g., Western blotting for phosphorylated proteins).
• Pharmacological inhibition of PI3K and Akt kinases, followed by assessment of protein synthesis rates using metabolic labeling.

Main Results:

• Akt kinase phosphorylation was abundant in gastric biopsies from H. pylori-infected patients.
• H. pylori infection activated Akt, mTOR, and S6 in a T4SS-independent manner, dependent on PI3K and Src family kinases.
• The pathway activation led to increased protein synthesis, evidenced by enhanced [(35)S]methionine/cysteine incorporation, which was reversed by PI3K inhibition.

Conclusions:

• H. pylori infection activates the PI3K/Akt/mTOR signaling pathway, influencing glycolysis and protein synthesis.
• This activation promotes cellular growth and proliferation, potentially contributing to H. pylori-related gastric pathophysiology.
• Targeting this pathway could offer therapeutic strategies for H. pylori-induced gastric diseases.