• norsk
    • English
  • English 
    • norsk
    • English
  • Login
View Item 
  •   Home
  • Øvrige samlinger
  • Publikasjoner fra CRIStin - NTNU
  • View Item
  •   Home
  • Øvrige samlinger
  • Publikasjoner fra CRIStin - NTNU
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation

Visnes, Torkild; Armando, Cazares-Körner; Wenjing, Hao; Wallner, Olov; Masuyer, Geoffrey; Loseva, Olga; Mortusewicz, Oliver; Wiita, Elisee; Sarno, Antonio; Manoilov, Aleksandr; Astorga-Wells, Juan; Jemth, Ann-Sofie; Pan, Lang; Sanjiv, Kumar; Karsten, Stella; Gokturk, Camilla; Grube, Maurice; Evert J, Homan; Hanna, Bishoy Magdi Fekry; Cynthia, Paulin BJ; pham, Therese; Rasti, Azita; Warpman Berglund, Ulrika; von Nikolai, Catharina; Benitez-Buelga, Carlos; Koolmeister, Tobias; Ivanic, Dag; Iliev, Petar; Scobie, Martin; Krokan, Hans Einar; Baranczewski, Pawel; Artursson, Per; Altun, Mikael; Jenmalm-Jensen, Annika; Kalderen, Christina; Xueqing, Ba; Zubarev, Roman A.; Stenmark, Pål; Boldogh, Istvan; Helleday, Thomas
Journal article, Peer reviewed
Accepted version
Thumbnail
View/Open
Science+manuscript+for+upload.pdf (4.439Mb)
URI
http://hdl.handle.net/11250/2577000
Date
2018
Metadata
Show full item record
Collections
  • Institutt for klinisk og molekylær medisin [2066]
  • Publikasjoner fra CRIStin - NTNU [20734]
Original version
Science. 2018, 362 (6416), 834-839.   10.1126/science.aar8048
Abstract
The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor κB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.
Publisher
American Association for the Advancement of Science
Journal
Science

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit
 

 

Browse

ArchiveCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDocument TypesJournalsThis CollectionBy Issue DateAuthorsTitlesSubjectsDocument TypesJournals

My Account

Login

Statistics

View Usage Statistics

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit