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DOI | 10.1126/science.aar8048 |
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation | |
Visnes, Torkild1,2; Cazares-Korner, Armando1,14; Hao, Wenjing3; Wallner, Olov1; Masuyer, Geoffrey4; Loseva, Olga1; Mortusewicz, Oliver1; Wiita, Elisee1; Sarno, Antonio5,6; Manoilov, Aleksandr7,8; Astorga-Wells, Juan7,8; Jemth, Ann-Sofie1; Pan, Lang3,15; Sanjiv, Kumar1; Karsten, Stella1; Gokturk, Camilla1; Grube, Maurice1; Homan, Evert J.1; Hanna, Bishoy M. F.1; Paulin, Cynthia B. J.1; Pham, Therese1; Rasti, Azita1; Berglund, Ulrika Warpman1; von Nicolai, Catharina1; Benitez-Buelga, Carlos1; Koolmeister, Tobias1; Ivanic, Dag1; Iliev, Petar1; Scobie, Martin1; Krokan, Hans E.5,6; Baranczewski, Pawel7,9,10; Artursson, Per9,10; Altun, Mikael1; Jensen, Annika Jenmalm11; Kalderen, Christina1; Ba, Xueqing3,16; Zubarev, Roman A.7,8,12; Stenmark, Pal4,13; Boldogh, Istvan3; Helleday, Thomas1 | |
2018-11-16 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6416页码:834-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Sweden; Norway; USA; Russia; Peoples R China |
英文摘要 | 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-alpha-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor kappa B 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000450488500054 |
WOS关键词 | OXIDATIVE DNA-DAMAGE ; 8-OXOGUANINE-DNA GLYCOSYLASE ; BASE MODIFICATIONS ; REPAIR ENZYME ; CELLS ; TRANSCRIPTION ; SITE ; DEMETHYLATION ; SPECIFICITY ; DEFICIENCY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200091 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, S-17176 Stockholm, Sweden; 2.SINTEF Ind, Dept Biotechnol & Nanomed, N-7465 Trondheim, Norway; 3.Univ Texas Med Branch, Sealy Ctr Mol Med, Dept Microbiol & Immunol, Galveston, TX 77555 USA; 4.Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden; 5.Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway; 6.Liaison Comm Educ Res & Innovat Cent Norway, Trondheim, Norway; 7.Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden; 8.SciLifeLab, SE-17121 Solna, Sweden; 9.Uppsala Univ, Dept Pharm, ADME Therapeut Facil, Sci Life Lab Drug Discovery & Dev Platform, Uppsala, Sweden; 10.Uppsala Univ, Dept Pharm, Uppsala Drug Optimisat & Pharmaceut Profiling Pla, Uppsala, Sweden; 11.Karolinska Inst, Chem Biol Consortium Sweden, Sci Life Lab, Div Translat Med & Chem Biol,Dept Med Biochem & B, S-17121 Stockholm, Sweden; 12.IM Sechenov First Moscow State Med Univ, Dept Pharmacol & Technol Chem, Moscow, Russia; 13.Lund Univ, Dept Expt Med Sci, Lund, Sweden; 14.Karolinska Univ Hosp, Dept Clin Pharmacol, SE-14186 Stockholm, Sweden; 15.Cent S Univ, Xiangya Med Sch, Dept Physiol, Changsha 410078, Hunan, Peoples R China; 16.Northeast Normal Univ, Sch Life Sci, Minist Educ, Key Lab Mol Epigenet, Changchun 130024, Jilin, Peoples R China |
推荐引用方式 GB/T 7714 | Visnes, Torkild,Cazares-Korner, Armando,Hao, Wenjing,et al. Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation[J]. SCIENCE,2018,362(6416):834-+. |
APA | Visnes, Torkild.,Cazares-Korner, Armando.,Hao, Wenjing.,Wallner, Olov.,Masuyer, Geoffrey.,...&Helleday, Thomas.(2018).Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation.SCIENCE,362(6416),834-+. |
MLA | Visnes, Torkild,et al."Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation".SCIENCE 362.6416(2018):834-+. |
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