title: 8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via Rac1/STATs signaling in LPS-induced brain microglia.
abstract: Free 8-hydroxydeoxyguanosine (oh(8)dG), a nucleoside of 8-hydroxyguanine (oh(8)Gua), present in cytosol is not incorporated into DNA. However, nothing is known about its biological function when it presents in cytosol as a free form. We demonstrate here for the first time that oh(8)dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh(8)dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1beta, IL-6, and TNF-alpha, in activated BV2 cells. We also found that oh(8)dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh(8)dG suppressed recruitment of STATs and p300 to the iNOS and COX-2 promoters, and inhibited H3 histone acetylation. Taken together, these results provide new aspects of oh(8)dG as an anti-inflammatory agent.
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Chungno-gu, Seoul 110-799, Korea.
authors.forename: Hong Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.forename: Ik Hyun
authors.initials: IH
authors.lastname: Cho
authors.forename: Joo Eun
authors.initials: JE
authors.lastname: Jung
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Seongwon
authors.initials: S
authors.lastname: Choi
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Chung
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009573:Nitrites; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050791:STAT Transcription Factors; D009569:Nitric Oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D020830:rac1 GTP-Binding Protein; D003849:Deoxyguanosine