S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via Rac1/STATs signaling in LPS-induced brain microglia
- Issue Date
- Free Radic Biol Med. 2006 Nov 1;41(9):1392-403. Epub 2006 Jul 27.
- Animals ; Blotting, Western ; Brain/*drug effects/metabolism ; Cells, Cultured ; Chromatin Immunoprecipitation ; Cyclooxygenase 2/genetics/*metabolism ; Deoxyguanosine/*analogs & derivatives/pharmacology ; E1A-Associated p300 Protein/metabolism ; Lipopolysaccharides/*pharmacology ; Luciferases/metabolism ; Male ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Microglia/cytology/*drug effects/metabolism ; Nitric Oxide/*metabolism ; Nitrites/metabolism ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Reactive Oxygen Species/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; STAT Transcription Factors/*metabolism ; Transcription, Genetic ; rac1 GTP-Binding Protein/*metabolism
- 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.
- 0891-5849 (Print)
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