Effect of Inhibition of Extracellular Signal-Regulated Kinase 1 and 2 Pathway on Apoptosis andbcl-2Expression inHelicobacter pylori-Infected AGS Cells

Open Access
Publisher Website
Google Scholar
Abstract
Helicobacter pyloriinduces activation of mitogen-activated protein kinases (MAPKs). However, its effect onH. pylori-induced apoptosis has not been evaluated. Thus, we examined whetherH. pylori-induced extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 MAPK activation affects gastric epithelial cell apoptosis andbcl-2family gene expression, especially in relation to thecagAstatus of anH. pyloristrain. In flow cytometric and oligonucleosome-bound DNA enzyme-linked immunosorbent assay analyses, infection withcagA+H. pyloristrains induced gastric cancer cell apoptosis in AGS cells more prominently than infection withcagAmutants. Activation of ERK1/2 and p38 MAPKs was also more prominent incagA+strains. Pretreatment with a MEK inhibitor (PD98059) inhibited ERK1/2 activation and increasedH. pylori-induced apoptosis significantly. This increased apoptosis was accompanied by decreased antiapoptoticbcl-2mRNA expression amongbcl-2-related genes (bcl-2,bax,bak,mcl-1, andbcl-XL/S), and the effect was also more prominent in thecagA+strains. However, the alteration ofbcl-2gene expression was not accompanied by protein level changes. Inhibition of p38 using specific inhibitor SB203580 decreasedH. pylori-induced apoptosis but resulted in little alteration ofbcl-2-related gene expression. In conclusion,H. pylori-induced ERK1/2 activation, especially by thecagA+H. pyloristrain, may play a protective role against gastric epithelial cell apoptosis partially through maintenance ofbcl-2gene expression.