title: Gastric epithelial cell death caused by Helicobacter suis and Helicobacter pylori      γ-glutamyl transpeptidase is mainly glutathione degradation-dependent.
abstract: Helicobacter (H.) suis is the most prevalent non-H. pylori Helicobacter species colonizing the stomach of humans suffering from gastric disease. In the present study, we aimed to unravel the mechanism used by H. suis to induce gastric epithelial cell damage. H. suis lysate induced mainly apoptotic death of human gastric epithelial cells. Inhibition of γ-glutamyl transpeptidase (GGT) activity present in H. suis lysate and incubation of AGS cells with purified native and recombinant H. suis GGT showed that this enzyme was partly responsible for the observed apoptosis. Supplementation of H. suis or H. pylori GGT-treated cells with glutathione strongly enhanced the harmful effect of both enzymes and resulted in the induction of oncosis/necrosis, demonstrating that H. suis and H. pylori GGT-mediated degradation of glutathione and the resulting formation of glutathione degradation products play a direct and active role in the induction of gastric epithelial cell death. This was preceded by an increase of extracellular H(2)O(2) concentrations, generated in a cell-independent manner and causing lipid peroxidation. In conclusion, H. suis and H. pylori GGT-mediated generation of pro-oxidant glutathione degradation products brings on cell damage and causes apoptosis or necrosis, dependent on the amount of extracellular glutathione available as a GGT substrate.
authors: Department of Pathology, Bacteriology and Avian Diseases, Ghent University, Merelbeke, Belgium. Bram.Flahou@UGent.be
authors: Bram
authors: B
authors: Flahou
authors: Freddy
authors: F
authors: Haesebrouck
authors: Koen
authors: K
authors: Chiers
authors: Kim
authors: K
authors: Van Deun
authors: Lina
authors: L
authors: De Smet
authors: Bart
authors: B
authors: Devreese
authors: Isabel
authors: I
authors: Vandenberghe
authors: Herman
authors: H
authors: Favoreel
authors: Annemieke
authors: A
authors: Smet
authors: Frank
authors: F
authors: Pasmans
authors: Katharina
authors: K
authors: D'Herde
authors: Richard
authors: R
authors: Ducatelle
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D057075:Enzyme Assays; D004847:Epithelial Cells / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D016998:Helicobacter / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D016481:Helicobacter Infections / Q000382:microbiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D015227:Lipid Peroxidation; D053078:Membrane Potential, Mitochondrial; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D013270:Stomach / Q000382:microbiology; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D007555:Isoxazoles; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C006303:acivicin