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Small-molecule inhi...
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
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- Visnes, Torkild (author)
- Karolinska Institute,Foundation for Scientific and Industrial Research (SINTEF)
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- Cázares-Körner, Armando (author)
- Karolinska Institute
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- Hao, Wenjing (author)
- Univ Texas Med Branch, Sealy Ctr Mol Med, Dept Microbiol & Immunol, Galveston, TX 77555 USA,University of Texas Medical Branch
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- Wallner, Olov (author)
- Karolinska Institute,Karolinska Institutet
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- Masuyer, Geoffrey (author)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden
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- Loseva, Olga (author)
- Karolinska Institute,Karolinska Institutet
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- Mortusewicz, Oliver (author)
- Karolinska Institute,Karolinska Institutet
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- Wiita, Elisée (author)
- Karolinska Institute,Karolinska Institutet
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- Sarno, Antonio (author)
- Karolinska Institutet,Norwegian University of Science and Technology
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- Manoilov, Aleksandr (author)
- Karolinska Institute,Science for Life Laboratory (SciLifeLab)
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- Astorga-Wells, Juan (author)
- Karolinska Institute,Science for Life Laboratory (SciLifeLab)
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- Jemth, Ann-Sofie (author)
- Karolinska Institute
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- Pan, Lang (author)
- Univ Texas Med Branch, Sealy Ctr Mol Med, Dept Microbiol & Immunol, Galveston, TX 77555 USA;Cent S Univ, Xiangya Med Sch, Dept Physiol, Changsha 410078, Hunan, Peoples R China,University of Texas Medical Branch
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- Sanjiv, Kumar (author)
- Karolinska Institute,Karolinska Institutet
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- Karsten, Stella (author)
- Karolinska Institute,Karolinska Institutet
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- Gokturk, Camilla (author)
- Karolinska Institute
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- Grube, Maurice (author)
- Karolinska Institute,Karolinska Institutet
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- Homan, Evert J. (author)
- Karolinska Institute,Karolinska Institutet
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- Hanna, Bishoy M. F. (author)
- Karolinska Institute,Karolinska Institutet
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- Paulin, Cynthia B. J. (author)
- Karolinska Institute,Karolinska Institutet
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- Pham, Therese (author)
- Karolinska Institute,Karolinska Institutet
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- Rasti, Azita (author)
- Karolinska Institute,Karolinska Institutet
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- Warpman Berglund, Ulrika (author)
- Karolinska Institute,Karolinska Institutet
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- von Nicolai, Catharina (author)
- Karolinska Institute
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- Benitez-Buelga, Carlos (author)
- Karolinska Institute
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- Koolmeister, Tobias (author)
- Karolinska Institute,Karolinska Institutet
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- Ivanic, Dag (author)
- Karolinska Institute
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- Iliev, Petar (author)
- Karolinska Institute
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- Scobie, Martin (author)
- Karolinska Institute,Karolinska Institutet
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- Krokan, Hans E. (author)
- Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway;Liaison Comm Educ Res & Innovat Cent Norway, Trondheim, Norway,Norwegian University of Science and Technology
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- Baranczewski, Pawel (author)
- Uppsala University,Karolinska Institute,Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden,Science for Life Laboratory (SciLifeLab)
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- Artursson, Per (author)
- Uppsala University,Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab
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- Altun, Mikael (author)
- Karolinska Institute,Karolinska Institutet
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- Jenmalm Jensen, Annika (author)
- Karolinska Institute,Karolinska Institutet
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- Kalderén, Christina (author)
- Karolinska Institute,Karolinska Institutet
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- Ba, Xueqing (author)
- Univ Texas Med Branch, Sealy Ctr Mol Med, Dept Microbiol & Immunol, Galveston, TX 77555 USA;Northeast Normal Univ, Sch Life Sci, Minist Educ, Key Lab Mol Epigenet, Changchun 130024, Jilin, Peoples R China,University of Texas Medical Branch
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- Zubarev, Roman A. (author)
- Karolinska Institute,Science for Life Laboratory (SciLifeLab),I.M. Sechenov First Moscow State Medical University
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- Stenmark, Pål (author)
- Stockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden;Lund Univ, Dept Expt Med Sci, Lund, Sweden,Strukturell biokemi,Forskargrupper vid Lunds universitet,Structural Biochemistry,Lund University Research Groups
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- Boldogh, Istvan (author)
- Univ Texas Med Branch, Sealy Ctr Mol Med, Dept Microbiol & Immunol, Galveston, TX 77555 USA,University of Texas Medical Branch
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- Helleday, Thomas (author)
- Karolinska Institute,Karolinska Institutet,University of Sheffield
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2018
- 2018
- English.
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 362:6416, s. 834-
- Related links:
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https://europepmc.or...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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https://lup.lub.lu.s...
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Science
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To the university's database
- By the author/editor
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Visnes, Torkild
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Cázares-Körner, ...
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Hao, Wenjing
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Wallner, Olov
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Masuyer, Geoffre ...
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Loseva, Olga
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show more...
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Mortusewicz, Oli ...
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Wiita, Elisée
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Sarno, Antonio
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Manoilov, Aleksa ...
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Astorga-Wells, J ...
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Jemth, Ann-Sofie
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Pan, Lang
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Sanjiv, Kumar
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Karsten, Stella
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Gokturk, Camilla
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Grube, Maurice
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Homan, Evert J.
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Hanna, Bishoy M. ...
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Paulin, Cynthia ...
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Pham, Therese
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Rasti, Azita
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Warpman Berglund ...
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von Nicolai, Cat ...
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Benitez-Buelga, ...
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Koolmeister, Tob ...
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Ivanic, Dag
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Iliev, Petar
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Scobie, Martin
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Krokan, Hans E.
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Baranczewski, Pa ...
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Artursson, Per
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Altun, Mikael
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Jenmalm Jensen, ...
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Kalderén, Christ ...
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Ba, Xueqing
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Zubarev, Roman A ...
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Stenmark, Pål
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Boldogh, Istvan
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Helleday, Thomas
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MEDICAL AND HEAL ...
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MEDICAL AND HEAL ...
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Science
- By the university
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Stockholm University
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Uppsala University
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Karolinska Institutet
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Lund University