Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role

Figure 1 Biochemical features and physiological role of Helicobacter pylori gamma-glutamyl transpeptidase. Helicobacter pylori (H. pylori) gamma-glutamyl transpeptidase (GGT) is a secreted protein of 40 and 20 kDs subunits that converts glutamine to glutamate and ammonia, and glutathione to glutamate and cysteinylglycine. The glutamate produced is then transported into H. pylori cells, where it is incorporated into the tricarboxylic acid (TCA) cycle or utilized for glutamine synthesis.

Figure 2 Effects of Helicobacter pylori gamma-glutamyl transpeptidase on gastric epithelial cells. Helicobacter pylori (H. pylori) gamma-glutamyl transpeptidase (GGT) causes consumption of mucosal glutamine and glutathione, production of ammonia and generation of ROS. These products induce caspase activation and apoptosis, ATP-depletion and necrosis, and cell-cycle arrest at G1-S phase in gastric epithelial cells. The effect of vacuolating cytotoxin (VacA) on caspase activation and apoptosis of gastric epithelial cells is also shown. H. pylori GGT may also inhibit apoptosis and induce proliferation through p38 MAPKs, AKT and NF-κB activation and subsequent COX-2, iNOS, growth factors and interleukin-8 (IL-8) induction. ROS: Reactive oxygen species; p38 MAPK: p38 mitogen-activated protein kinase; PI3K: Phosphatidylinositide 3-kinase; AKT: AKT kinase; NF-κB: Nuclear factor κB; COX-2: Cyclo-oxygenase 2; iNOS: Inducible nitric oxide synthase; PG: Prostaglandin.

Figure 3 Effects of Helicobacter pylori gamma-glutamyl transpeptidase on T cell-mediated immunity. Helicobacter pylori gamma-glutamyl transpeptidase (GGT) and VacA inhibit T cell proliferation and differentiation to T helper 1 (T_H1) and T_H17. They also prevent T cell immunity by reprogramming dendritic cells to produce interleukin-10 (IL-10) and IL-18 and promote the differentiation of naive T cells into T regulatory (Treg) cells that further suppress T_H1 and T_H17 effector functions. FOXP3: Forkhead box P3; NFAT: Nuclear factor of activated T cells; IFN-γ: Interferon gamma.