Lv Guoqiang, Zhu Huanhuan, Zhou Feng, Lin Zhou, Lin Gang, Li Chenwan
Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
Biochem Biophys Res Commun. 2014 Oct 10;453(1):13-8. doi: 10.1016/j.bbrc.2014.09.028. Epub 2014 Sep 16.
Helicobacter pylori (H pylori), infecting half of the world's population, causes gastritis, duodenal and gastric ulcer, and gastric cancers. AMP-activated protein kinase (AMPK) is a highly conserved regulator of cellular energy and metabolism. Recent studies indicated an important role for AMPK in promoting cell survival. In this study, we discovered that H Pylori induced AMPK activation in transformed (GEC-1 line) and primary human gastric epithelial cells (GECs). Inhibition of H Pylori-stimulated AMPK kinase activity by AMPK inhibitor compound C exacerbated apoptosis in transformed and primary GECs. Meanwhile, downregulation of AMPK expression by targeted shRNAs promoted apoptosis in H pylori-infected GECs. In contrast, A-769662 and resveratrol, two known AMPK activators, or AMPKα1 over-expression, enhanced H Pylori-induced AMPK activation, and inhibited GEC apoptosis. Our data suggested that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) could be the upstream kinase for AMPK activation by H pylori. Partial depletion of TAK1 by shRNAs not only inhibited AMPK activation, but also suppressed survival of H pylori-infected GECs. Taken together, these results suggest that TAK1-dependent AMPK activation protects GECs from H pylori-Induced apoptosis.
幽门螺杆菌（H pylori）感染了全球一半的人口，可导致胃炎、十二指肠溃疡和胃溃疡以及胃癌。AMP激活的蛋白激酶（AMPK）是细胞能量和代谢的高度保守调节因子。最近的研究表明AMPK在促进细胞存活中起重要作用。在本研究中，我们发现幽门螺杆菌在转化的（GEC-1系）和原代人胃上皮细胞（GECs）中诱导AMPK激活。AMPK抑制剂化合物C抑制幽门螺杆菌刺激的AMPK激酶活性会加剧转化的和原代GECs中的细胞凋亡。同时，靶向shRNA下调AMPK表达会促进幽门螺杆菌感染的GECs中的细胞凋亡。相反，两种已知的AMPK激活剂A-769662和白藜芦醇，或AMPKα1过表达，增强了幽门螺杆菌诱导的AMPK激活，并抑制了GEC细胞凋亡。我们的数据表明，转化生长因子-β（TGF-β）激活的激酶1（TAK1）可能是幽门螺杆菌激活AMPK的上游激酶。shRNA部分耗尽TAK1不仅抑制AMPK激活，还抑制幽门螺杆菌感染的GECs的存活。综上所述，这些结果表明TAK1依赖性AMPK激活可保护GECs免受幽门螺杆菌诱导的细胞凋亡。
