Differential regulation of ERK1/2 and p38 MAP kinases in VacA-induced apoptosis of gastric epithelial cells

被引:42
作者
Ki, Mi-Ran [1 ]
Lee, Hye-Rim [1 ]
Goo, Moon-Jung [1 ]
Hong, Il-Hwa [1 ]
Do, Sun-Hee [1 ]
Jeong, Da-Hee [1 ]
Yang, Hai-Jie [1 ]
Yuan, Dong-Wei [1 ]
Park, Jin-Kyu [1 ]
Jeong, Kyu-Shik [1 ]
机构
[1] Kyungpook Natl Univ, Dept Pathol, Coll Vet Med, Taegu 702701, South Korea
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2008年 / 294卷 / 03期
关键词
Helicobacter pylori; VacA; SOD-1; villin; MAP kinase signaling;
D O I
10.1152/ajpgi.00281.2007
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Helicobacter pylori vacuolating cytotoxin A (VacA) has been considered as an apoptosis-inducing factor. Here, we investigated the mechanism of VacA-induced apoptosis in relation to the defense mechanism and MAP kinases pathway in gastric epithelial cells. AGS cells exposed to enriched VacA extracts affected the level of SOD-1 and villin. We further investigated the role of VacA in those inductions using a functional recombinant VacA (rVacA). Activation of p38 MAPK and Bax dimerization by rVacA were increased in a dose-dependent manner. rVacA- induced ERK1/2 MAPK activation was maximal at 30 min and 4 h and 1-4 mu g/ml of rVacA. rVacA- induced SOD-1 expression was considerably diminished by inhibiting ERK1/2 MAPK and it was slightly increased by inhibiting p38 MAPK. rVacA increased or decreased villin expression depending on dose and exposure time and its expression was mainly appeared in the contractile actin ring of the dividing cells. Despite its cytoprotective effect, SB-203580, a p38 inhibitor, was unlikely to reduce VacA-induced Bax dimerization and rather inhibited villin and Bc12 expression, indicating that p38 may also play a role in cell proliferation or differentiation for survival after VacA intoxication. Furthermore, p38 inhibitor accelerated rVacA-induced cell death after exposure of AGS cells to H2O2 but ERK1/2 inhibitor protected cells from H2O2 insult. These results suggest that SOD-1 and villin are expressed differentially upon VacA insult depending on dose and exposure time via ERK and p38 MAP kinases; decrease in SOD-1 and villin expression coupled with Bax dimerization leads to apoptosis of gastric epithelial cells.
引用
收藏
页码:G635 / G647
页数:13
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