title: Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis.
abstract: Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK-HO-1 signaling.
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
authors.forename: Hangyong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Wuxi Third People's Hospital of Nantong University, Wuxi 214041, China.
authors.forename: Huanghuang
authors.initials: H
authors.lastname: Zhu
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. Electronic address: lvguoqiangwuxivip@163.com.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Lv
mesh_terms: D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D020536:Enzyme Activators; D017382:Reactive Oxygen Species; D000263:Adenylate Kinase
keywords: AMPK; Apoptosis; Compound 13; Gastric epithelial cells; HO-1; Helicobacter pylori; Reactive oxygen species (ROS)