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8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via Rac1/STATs signaling in LPS-induced brain microglia

Cited 40 time in Web of Science Cited 43 time in Scopus
Authors
Kim, Hong sook; Ye, Sang-Kyu; Cho, Ik Hyun; Jung, Joo Eun; Kim, Dong-Hyun; Choi, Seongwon; Kim, Yong-Sik; Park, Chung-Gyu; Kim, Tae-Yoon; Lee, Jung Weon; Chung, Myung-Hee
Issue Date
2006-10-07
Publisher
Elsevier
Citation
Free Radic Biol Med. 2006 Nov 1;41(9):1392-403. Epub 2006 Jul 27.
Keywords
AnimalsBlotting, WesternBrain/*drug effects/metabolismCells, CulturedChromatin ImmunoprecipitationCyclooxygenase 2/genetics/*metabolismDeoxyguanosine/*analogs & derivatives/pharmacologyE1A-Associated p300 Protein/metabolismLipopolysaccharides/*pharmacologyLuciferases/metabolismMaleMembrane Proteins/genetics/*metabolismMiceMice, Inbred C57BLMicroglia/cytology/*drug effects/metabolismNitric Oxide/*metabolismNitrites/metabolismPromoter Regions, GeneticRNA, Messenger/genetics/metabolismReactive Oxygen Species/metabolismReverse Transcriptase Polymerase Chain ReactionSTAT Transcription Factors/*metabolismTranscription, Geneticrac1 GTP-Binding Protein/*metabolism
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.
ISSN
0891-5849 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17023266

http://hdl.handle.net/10371/24657
DOI
https://doi.org/10.1016/j.freeradbiomed.2006.07.018
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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