Document Detail


Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease.
MedLine Citation:
PMID:  20347814     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: gamma-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-kappaB (NF-kappaB) 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 H2O2 in primary gastric epithelial cells and AGS gastric cancer cells, resulting in the activation of NF-kappaB 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, Deltaggt 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.
Authors:
Min Gong; Samantha Shi Min Ling; Sook Yin Lui; Khay Guan Yeoh; Bow Ho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-27
Journal Detail:
Title:  Gastroenterology     Volume:  139     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-27     Completed Date:  2010-08-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  564-73     Citation Subset:  AIM; IM    
Copyright Information:
Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Bacterial Proteins / genetics,  metabolism*
Biopsy
Blotting, Western
Cells, Cultured
Chromatography, Gel
Chromatography, Ion Exchange
Comet Assay
DNA Damage
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Fluorometry
Gastric Mucosa / immunology,  microbiology*,  pathology
Helicobacter Infections / complications,  microbiology*,  pathology
Helicobacter pylori / enzymology,  genetics,  pathogenicity*
Humans
Hydrogen Peroxide / metabolism
Interleukin-8 / genetics,  metabolism
Mutation
NF-kappa B / metabolism
Oxidative Stress
Reverse Transcriptase Polymerase Chain Reaction
Stomach Ulcer / immunology,  microbiology*,  pathology
Time Factors
Virulence Factors / genetics,  metabolism*
gamma-Glutamyltransferase / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/IL8 protein, human; 0/Interleukin-8; 0/NF-kappa B; 0/Virulence Factors; 7722-84-1/Hydrogen Peroxide; EC 2.3.2.2/gamma-Glutamyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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