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|Title:||Helicobacter pylori γ-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease|
Peptic Ulcer Disease
Reactive Oxygen Species
|Citation:||Gong, M., Ling, S.S.M., Lui, S.Y., Yeoh, K.G., Ho, B. (2010). Helicobacter pylori γ-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology 139 (2) : 564-573. ScholarBank@NUS Repository.|
|Abstract:||Background & Aims: γ-Glutamyl transpeptidase (GGT) has been reported to be a virulence factor of Helicobacter pylori associated with bacterial colonization and cell apoptosis. But its mechanism of pathogenesis is not firmly established. This study aims to examine its role in H pylori-mediated infection. Methods: Various H pylori isogenic mutants were constructed by a polymerase chain reaction (PCR) approach. H pylori native GGT protein (HP-nGGT) was purified with ion-exchange and gel-filtration chromatography. Generation of H2O2 was measured with fluorimetric analysis, whereas nuclear factor-κB (NF-κB) activation was determined by luciferase assay and Western blot. Cytokine production was examined by enzyme-linked immunoabsorbent assay and real-time PCR. DNA damage was assessed with comet assay and flow cytometry. The GGT activity of 98 H pylori isolates was analyzed by an enzymatic assay. Results: Purified HP-nGGT generated H2O 2 in primary gastric epithelial cells and AGS gastric cancer cells, resulting in the activation of NF-κB and up-regulation of interleukin-8 (IL-8) production. In addition, HP-nGGT caused an increase in the level of 8-OH-dG, indicative of oxidative DNA damage. In contrast, Δggt showed significantly reduced levels of H2O2 generation, IL-8 production, and DNA damage in cells compared with the wild type (P < .05). The clinical importance of GGT was indicated by significantly higher (P < .001) activity in H pylori isolates obtained from patients with peptic ulcer disease (n = 54) than isolates from patients with nonulcer dyspepsia (n = 44). Conclusion: Our findings provide evidence that GGT is a pathogenic factor associated with H pylori-induced peptic ulcer disease. © 2010 AGA Institute.|
|Appears in Collections:||Staff Publications|
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