Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration and gastric carcinoma. Proteomic analysis of the human gastric mucosa from the patients with erosive gastritis, peptic ulcer or gastric cancer, which were either infected or not with H. pylori, was used to determine the differentially expressed proteins by H. pylori in the human gastric mucosa in order to investigate the pathogenic mechanism of H. pylori-induced gastric diseases. Prior to the experiment, the expression of the main 18 proteins were identified in the gastric mucosa and used for a proteome map of the human gastric mucosa. Using two-dimensional electrophoresis of the protein isolated from the H. pylori-infected tissues, Coomassie Brilliant Blue staining and computerized analysis of the stained gel, the expression of eight proteins were altered in the H. pylori-infected tissues compared with the non-infected tissues. MS analysis (matrix-assisted laser desorption/ionization–time of flight MS) of the tryptic fragment and a data search allowed the the identification of the four increased proteins (78 kDa glucose-regulated protein precursor, endoplasmin precursor, aldehyde dehydrogenase 2 and l-lactate dehydrogenase B chain) and the four decreased proteins (intracellular chloride channel protein 1, glutathione S-transferase, heat-shock protein 60 and cytokeratin 8) caused by H. pylori infection in the gastric mucosa. These proteins are related to cell proliferation, carcinogenesis, cytoskeletal function and cellular defence mechanism. The common feature is that these proteins are related to oxidative-stress-mediated cell damage. In conclusion, the established gastric mucosal proteome map might be useful for detecting the disease-related protein changes. The H. pylori-induced alterations in protein expression demonstrate the involvement of oxidative stress in the pathogenesis of H. pylori-induced gastric diseases, including inflammation, ulceration and carcinogenesis.
- gastric mucosa
- Helicobacter pylori
- reactive oxygen species
- two-dimensional electrophoresis
Abbreviations used: GRP78, 78 kDa glucose-regulated protein precursor; ALDH, aldehyde dehydrogenase; LDH, l-lactate dehydrogenase; GST, glutathione S-transferase; Hsp, heat-shock protein; CK, cytokeratin; ROS, reactive oxygen species; 2-DE, two-dimensional electrophoresis; CBB, Coomassie Brilliant Blue; MALDI-TOF MS, matrix-assisted laser-desorption/ionization–time-of-flight MS; cagA, cytotoxin-associated gene; NF-κB, nuclear factor κB; AP-1, activator protein 1; MAPK, mitogen-activated protein kinase; IPG, immobilized pH gradient; TFA, trifluoroacetic acid; ER, endoplasmic reticulum.
- The Biochemical Society, London ©2004