Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
Int J Biochem Cell Biol. 2010 Sep;42(9):1455-61. doi: 10.1016/j.biocel.2010.04.015. Epub 2010 May 6.
Reactive oxygen species (ROS) are involved in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric disorders including inflammation. NADPH oxidase has been considered as a major source of ROS in phagocytic and non-phagocytic cells. Small G protein Rac1 is one components of NADPH oxidase complex. Heat shock protein 90 kDa (HSP90) modulates cytokine production in H. pylori-infected gastric epithelial cells. The present study aims to investigate the relation of HSP90beta and Rac1 on the activation of NADPH oxidase in H. pylori-infected gastric epithelial cells. As a result, H. pylori-induced translocation of HSP90beta from the cytosol to the membrane and activated Rac1 in gastric epithelial AGS cells. HSP90beta physically interacted with Rac1, which resulted in the activation of NADPH oxidase in H. pylori-infected AGS cells. Down-regulation of HSP90beta by transfection of HSP90beta siRNA suppressed the activation of Rac1, activity of NADPH oxidase and the production of H(2)O(2) in H. pylori-infected AGS cells. In conclusion, H. pylori induces the translocation of HSP90beta from the cytosol to the membrane and interaction of HSP90beta and Rac1, which leads to the activation of NADPH oxidase and production of ROS in gastric epithelial cells. HSP90beta may be the target molecule for treatment of H. pylori-induced gastric injury.
活性氧（ROS）参与了幽门螺杆菌（H. pylori）引起的胃部疾病的发病机制，包括炎症。NADPH 氧化酶被认为是吞噬细胞和非吞噬细胞中 ROS 的主要来源。小 G 蛋白 Rac1 是 NADPH 氧化酶复合物的一个组成部分。热休克蛋白 90 kDa（HSP90）调节 H. pylori 感染胃上皮细胞中的细胞因子产生。本研究旨在探讨 HSP90β与 Rac1 在 H. pylori 感染胃上皮细胞中 NADPH 氧化酶激活中的关系。结果表明，H. pylori 诱导 HSP90β从细胞质向膜转位，并激活胃上皮细胞 AGS 中的 Rac1。HSP90β与 Rac1 发生物理相互作用，导致 H. pylori 感染的 AGS 细胞中 NADPH 氧化酶的激活。通过 HSP90β siRNA 的转染下调 HSP90β 抑制了 Rac1 的激活、NADPH 氧化酶的活性和 H. pylori 感染的 AGS 细胞中 H2O2 的产生。总之，H. pylori 诱导 HSP90β从细胞质向膜转位，并发生 HSP90β和 Rac1 的相互作用，导致胃上皮细胞中 NADPH 氧化酶的激活和 ROS 的产生。HSP90β 可能是治疗 H. pylori 引起的胃损伤的靶分子。
