Gastric epithelial cell death caused by Helicobacter suis and Helicobacter pylori γ-glutamyl transpeptidase is mainly glutathione degradation-dependent

被引：57

作者：

Flahou, Bram ^{[1
]}

Haesebrouck, Freddy ^{[1
]}

Chiers, Koen ^{[1
]}

Van Deun, Kim ^{[1
]}

De Smet, Lina ^{[3
]}

Devreese, Bart ^{[3
]}

Vandenberghe, Isabel ^{[3
]}

Favoreel, Herman ^{[2
]}

Smet, Annemieke ^{[1
]}

Pasmans, Frank ^{[1
]}

D'Herde, Katharina ^{[4
]}

Ducatelle, Richard ^{[1
]}

机构：

[1] Univ Ghent, Fac Vet Med, Dept Pathol Bacteriol & Avian Dis, Merelbeke, Belgium

[2] Univ Ghent, Fac Vet Med, Dept Virol Parasitol & Immunol, Merelbeke, Belgium

[3] Univ Ghent, Fac Sci, Dept Biochem & Microbiol, B-9000 Ghent, Belgium

[4] Univ Ghent, Fac Med & Hlth Sci, Dept Basic Med Sci, B-9000 Ghent, Belgium

来源：

CELLULAR MICROBIOLOGY | 2011年 / 13卷 / 12期

关键词：

REACTIVE OXYGEN; HYDROGEN-PEROXIDE; MONGOLIAN GERBILS; GENOME SEQUENCE; H2O2; PRODUCTION; MUCOSAL LIPOPEROXIDATION; LIQUID-CHROMATOGRAPHY; APOPTOSIS; HEILMANNII; INFECTION;

D O I：

10.1111/j.1462-5822.2011.01682.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 ?-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 H2O2 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.

引用

页码：1933 / 1955

页数：23

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