title: Effect of inhibition of extracellular signal-regulated kinase 1 and 2 pathway on apoptosis and bcl-2 expression in Helicobacter pylori-infected AGS cells.
abstract: Helicobacter pylori induces activation of mitogen-activated protein kinases (MAPKs). However, its effect on H. pylori-induced apoptosis has not been evaluated. Thus, we examined whether H. pylori-induced extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 MAPK activation affects gastric epithelial cell apoptosis and bcl-2 family gene expression, especially in relation to the cagA status of an H. pylori strain. In flow cytometric and oligonucleosome-bound DNA enzyme-linked immunosorbent assay analyses, infection with cagA(+) H. pylori strains induced gastric cancer cell apoptosis in AGS cells more prominently than infection with cagA mutants. Activation of ERK1/2 and p38 MAPKs was also more prominent in cagA(+) strains. Pretreatment with a MEK inhibitor (PD98059) inhibited ERK1/2 activation and increased H. pylori-induced apoptosis significantly. This increased apoptosis was accompanied by decreased antiapoptotic bcl-2 mRNA expression among bcl-2-related genes (bcl-2, bax, bak, mcl-1, and bcl-X(L/S)), and the effect was also more prominent in the cagA(+) strains. However, the alteration of bcl-2 gene expression was not accompanied by protein level changes. Inhibition of p38 using specific inhibitor SB203580 decreased H. pylori-induced apoptosis but resulted in little alteration of bcl-2-related gene expression. In conclusion, H. pylori-induced ERK1/2 activation, especially by the cagA(+) H. pylori strain, may play a protective role against gastric epithelial cell apoptosis partially through maintenance of bcl-2 gene expression.
authors.affiliation: Center for Gastric Cancer, National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Il Ju
authors.initials: IJ
authors.lastname: Choi
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.forename: Hyun Chae
authors.initials: HC
authors.lastname: Jung
authors.forename: In Sung
authors.initials: IS
authors.lastname: Song
mesh_terms: D000942:Antigens, Bacterial; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000382:microbiology; D005753:Gastric Mucosa / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C080866:cagA protein, Helicobacter pylori; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases