title: AMP-activated protein kinase activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China. Electronic address: guoqianglvlvdr@126.com.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
authors.forename: Chenwan
authors.initials: C
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001713:Biphenyl Compounds; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D005753:Gastric Mucosa / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D015870:Gene Expression; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D055372:AMP-Activated Protein Kinases; D001713:Biphenyl Compounds; D020930:MAP Kinase Kinase Kinases; D011753:Pyrones; D034741:RNA, Small Interfering; D000077185:Resveratrol; D013267:Stilbenes; D013876:Thiophenes; D000099151:MAP Kinase Kinase Kinase 7; C512408:4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile
keywords: AMPK; Apoptosis; Gastric epithelial cells; Helicobacter pylori; TAK1