HSP90β interacts with Rac1 to activate NADPH oxidase in Helicobacter pylori-infected gastric epithelial cells

HSP90β interacts with Rac1 to activate NADPH oxidase in Helicobacter pylori-infected gastric epithelial cells
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DOI:
10.1016/j.biocel.2010.04.015
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发表时间:
2010-09-01
影响因子:
4
通讯作者:
Kim, Hyeyong
Kim, Hyeyong
中科院分区:
生物学2区
文献类型:
--
作者:
Cha, Boram;Lim, Joo Weon;Kim, Hyeyong

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活性氧参与了幽门螺杆菌(H.幽门螺杆菌)引起的胃疾病,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氧化酶复合物的组成部分之一。热休克蛋白90(HSP 90)调节H.幽门感染的胃上皮细胞。本研究旨在探讨HSP90 P和Rac 1在H.幽门感染的胃上皮细胞。因此,H.幽门螺杆菌诱导的HSP90 β从胞浆到膜的易位和胃上皮AGS细胞中激活的Rac 1。HSP90 β与Rac1相互作用,导致NADPH氧化酶在H.幽门感染的AGS细胞。通过转染HSP90 β siRNA下调HSP90 β,抑制了H2O2的产生、NADPH氧化酶的活性和Rac1的活化。幽门感染的AGS细胞。最后,H. pylori感染诱导HSP90 β从胞浆易位到细胞膜,并诱导HSP90 β与Rac 1相互作用,从而导致胃上皮细胞中NADPH氧化酶的激活和ROS的产生。HSP90 β可能是治疗H.幽门损伤(C)2010爱思唯尔有限公司版权所有。
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 HSP90 P and Rac1 on the activation of NADPH oxidase in H. pylori-infected gastric epithelial cells. As a result, H. pylori-induced translocation of HSP90 beta from the cytosol to the membrane and activated Rac1 in gastric epithelial AGS cells. HSP90 beta physically interacted with Rac1, which resulted in the activation of NADPH oxidase in H. pylori-infected AGS cells. Down-regulation of HSP90 beta by transfection of HSP90 beta siRNA suppressed the activation of Rac1, activity of NADPH oxidase and the production of H2O2 in H. pylori-infected AGS cells. In conclusion, H. pylori induces the translocation of HSP90 beta from the cytosol to the membrane and interaction of HSP90 beta and Rac1, which leads to the activation of NADPH oxidase and production of ROS in gastric epithelial cells. HSP90 beta may be the target molecule for treatment of H. pylori-induced gastric injury. (C) 2010 Elsevier Ltd. All rights reserved.