HSP90beta interacts with Rac1 to activate NADPH oxidase in Helicobacter pylori-infected gastric epithelial cells.
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.
Cha
Boram
B
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.
Lim
Joo Weon
JW
Kim
Kyung Hwan
KH
Kim
Hyeyong
H
D015153:Blotting, Western; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D005753:Gastric Mucosa / Q000166:cytology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D016481:Helicobacter Infections / Q000382:microbiology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D034741:RNA, Small Interfering; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein