Kim Hyeyoung, Seo Ji Hye, Kim Kyung Hwan
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Ann N Y Acad Sci. 2003 Dec;1010:90-4. doi: 10.1196/annals.1299.014.
The loss of mucus coat continuity and apoptosis have been shown in Helicobacter pylori (H. pylori)-infected gastric tissues. Blockade of p38 mitogen-activated kinase (MAPK) produced reversal in the LPS-induced reduction in mucin synthesis and apoptosis in gastric epithelial cells. This study investigates whether H. pylori induces apoptosis, alterations in mucin gene (MUC) expression, and p38 MAPK activation in human gastric epithelial AGS cells. After treatment of AGS cells with H. pylori at the ratio of 1:300, apoptosis was determined by DNA fragmentation and DNA laddering. MUC expression was assessed by RT-PCR. p38 MAPK activation and mucin protein level, using anti-mucin antibody for MUC5/6, were determined by Western blot analysis. As a result, H. pylori induced apoptosis and loss of mucin, which was supported by reduced mRNA expression of MUC5AC by H. pylori in AGS cells. MUC7/8 expression and p38 MAPK activation were induced in H. pylori-infected AGS cells. In conclusion, H. pylori induces p38 MAPK activation, wh3.ich may be the underlying mechanism of alterations in MUC expression and apoptosis in gastric epithelial cells.
幽门螺杆菌（H. pylori）感染的胃组织中已出现黏液层连续性丧失和细胞凋亡。p38丝裂原活化蛋白激酶（MAPK）的阻断可逆转脂多糖（LPS）诱导的胃上皮细胞黏蛋白合成减少和细胞凋亡。本研究调查幽门螺杆菌是否会诱导人胃上皮AGS细胞发生细胞凋亡、黏蛋白基因（MUC）表达改变以及p38 MAPK激活。以1:300的比例用幽门螺杆菌处理AGS细胞后，通过DNA片段化和DNA梯状条带分析来测定细胞凋亡。通过逆转录聚合酶链反应（RT-PCR）评估MUC表达。使用针对MUC5/6的抗黏蛋白抗体，通过蛋白质免疫印迹分析来测定p38 MAPK激活和黏蛋白蛋白水平。结果显示，幽门螺杆菌诱导细胞凋亡和黏蛋白丢失，这在AGS细胞中表现为幽门螺杆菌使MUC5AC的mRNA表达降低。幽门螺杆菌感染的AGS细胞中诱导了MUC7/8表达和p38 MAPK激活。总之，幽门螺杆菌诱导p38 MAPK激活，这可能是胃上皮细胞中MUC表达改变和细胞凋亡的潜在机制。
