Open AccessHelicobacter pylori Protein JHP0290 Exhibits Proliferative and Anti-Apoptotic Effects in Gastric Epithelial Cells
Author(s) -
Raquel Tavares,
Sushil Kumar Pathak
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0124407
Subject(s) - helicobacter pylori , apoptosis , biology , gastric mucosa , mapk/erk pathway , cell growth , cell culture , microbiology and biotechnology , cell cycle , signal transduction , chemistry , stomach , biochemistry , genetics
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.