Effect of Inhibition of Extracellular Signal-Regulated Kinase 1 and 2 Pathway on Apoptosis and<i>bcl-2</i>Expression in<i>Helicobacter pylori</i>-Infected AGS Cells

• Il Ju Choi

  Center for Gastric Cancer, National Cancer Center, Goyang, Gyeonggi

• Joo Sung Kim

  Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, and Clinical Research Institute, Seoul National University Hospital

• Jung Mogg Kim

  Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea

• Hyun Chae Jung

  Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, and Clinical Research Institute, Seoul National University Hospital

• In Sung Song

  Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, and Clinical Research Institute, Seoul National University Hospital

抄録

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.

収録刊行物

• Infection and Immunity

  Infection and Immunity 71 (2), 830-837, 2003-02

  American Society for Microbiology

キーワード

• Infectious Diseases
• Immunology
• Microbiology
• Parasitology

詳細情報

• CRID: 1363670319803060608
• NII論文ID: 30020830817
• DOI: 10.1128/iai.71.2.830-837.2003
• ISSN: 10985522
• ISSN: 00199567
• Web Site: https://journals.asm.org/doi/pdf/10.1128/IAI.71.2.830-837.2003
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