title: Helicobacter pylori promotes eukaryotic protein translation by activating phosphatidylinositol 3 kinase/mTOR.
abstract: The innate immune response elicited by Helicobacter pylori in the human gastric mucosa involves a range of cellular signalling pathways, including those implicated in metabolism regulation. In this study, we analysed H. pylori-induced PI3K/Akt/mTOR signalling, which regulates glycolysis and protein synthesis and associates thereby with cellular energy- and nutrients-consuming processes such as growth and proliferation. The immunohistochemical analysis demonstrated that Akt kinase phosphorylation is abundant in gastric biopsies obtained from gastritis, gastric adenoma and adenocarcinoma patients. Infection with H. pylori led to the phosphorylation of Akt effectors mTOR and S6 in a type 4 secretion system (T4SS)-independent manner in AGS cells. We observed that the activation of these molecules was dependent on PI3K and the Src family tyrosine kinases. Furthermore, H. pylori induced the phosphorylation of 4E-BP1 and eIF4E and suppressed the phosphorylation of eEF2, which are important regulators of protein synthesis. Inhibition of PI3K and Akt kinase prevented the phosphorylation of 4E-BP1, suggesting that PI3K signalling is involved in the regulation of translation initiation during H. pylori infection. Metabolic labelling showed that infected cells had higher rates of [(35)S]methionine/cysteine incorporation, and this effect could be prevented using LY294002, an PI3K inhibitor. Thus, H. pylori activates PI3K/Akt signalling, mTOR, eIFs and protein translation, which might impact H. pylori-related gastric pathophysiology.
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany. Electronic address: olga.sokolova@med.ovgu.de.
authors.forename: Olga
authors.initials: O
authors.lastname: Sokolova
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Gnad
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Przemyslaw M
authors.initials: PM
authors.lastname: Bozko
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Naumann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D054736:Elongation Factor 2 Kinase / Q000378:metabolism; D004789:Enzyme Activation; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008875:Middle Aged; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; C517689:EEF2K protein, human; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D054736:Elongation Factor 2 Kinase
keywords: H. pylori; Protein synthesis; S6 ribosomal protein; eIF4; mTOR