Characterization of helicobacter pylori y-glutamyl transpeptidase and its role in pathogenesis

Abstract

Gamma-glutamyl transpeptidase (GGT) activity is constitutively expressed in all Helicobacter pylori strains. However, its role in gastroduodenal diseases is unknown. This project characterizes GGT and examines its role in H. pylori infections. The study shows that GGT is highly conserved and membrane-bound. H. pylori strains possessing high GGT activity proliferated more efficiently under in vitro conditions and are significantly associated with peptic ulcer disease (p<0.001). Native GGT protein was purified to >95% purity from H. pylori SS1 using repeated ion-exchange and size-exclusion chromatography which showed that it contains a large and a small subunits. Native GGT exhibited significantly higher cell apoptosis-inducing activity (p<0.05) which was dominantly signaled by mitochondrial-mediated signaling pathway. Furthermore, it induced hydrogen peroxide generation resulting in the elevated interlukin-8 production by activating NF-I?B in gastric epithelial cells. The novel findings provide a new focus on the cause and course of the H. pylori-associated gastroduodenal diseases.