title: Helicobacter pylori protein JHP0290 exhibits proliferative and anti-apoptotic effects in gastric epithelial cells.
abstract: The influence of Helicobacter pylori infection on gastric epithelial cell proliferation, apoptosis and signaling pathways contributes to the development of infection-associated diseases. Here we report that JHP0290, which is a poorly functionally characterized protein from H. pylori, regulates multiple responses in human gastric epithelial cells. The differential expression and release of JHP0290 homologues was observed among H. pylori strains. JHP0290 existed in monomeric and dimeric forms in H. pylori cell extracts and culture broth. Recombinant purified JHP0290 (rJHP0290) also showed monomeric and dimeric forms, whereas the rJHP0290 C162A mutant exhibited only a monomeric form. The dimeric form of the protein was found to bind more efficiently to gastric epithelial cells than the monomeric form. The exposure of gastric epithelial cells to rJHP0290 induced proliferation in a dose-dependent manner. Faster progression into the cell cycle was observed in rJHP0290-challenged gastric epithelial cells. Furthermore, we detected an anti-apoptotic effect of rJHP0290 in gastric epithelial cells when the cells were treated with rJHP0290 in combination with Camptothecin (CPT), which is an inducer of apoptosis. CPT-induced caspase 3 activation was significantly reduced in the presence of rJHP0290. In addition, the activation of ERK MAPK and the transcription factor NFκB was observed in rJHP0290-challenged gastric epithelial cells lines. Our results suggest that JHP0290 may affect H. pylori-induced gastric diseases via the regulation of gastric epithelial cell proliferation and anti-apoptotic pathways.
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors: Raquel
authors: R
authors: Tavares
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors: Sushil Kumar
authors: SK
authors: Pathak
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D001426:Bacterial Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000276:immunology; D011485:Protein Binding; D055503:Protein Multimerization; D013270:Stomach / Q000276:immunology / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D016328:NF-kappa B