DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kang, Sookjin | ko |
dc.contributor.author | Kim, Wooseong | ko |
dc.contributor.author | Jeong, Seongkeun | ko |
dc.contributor.author | Lee, Yonghyun | ko |
dc.contributor.author | Nam, Joon | ko |
dc.contributor.author | Lee, Sunyoung | ko |
dc.contributor.author | Jung, Yunjin | ko |
dc.date.accessioned | 2017-07-18T05:42:13Z | - |
dc.date.available | 2017-07-18T05:42:13Z | - |
dc.date.created | 2017-07-03 | - |
dc.date.created | 2017-07-03 | - |
dc.date.issued | 2017-07 | - |
dc.identifier.citation | FREE RADICAL BIOLOGY AND MEDICINE, v.108, pp.715 - 724 | - |
dc.identifier.issn | 0891-5849 | - |
dc.identifier.uri | http://hdl.handle.net/10203/224771 | - |
dc.description.abstract | Mesalazine (5-aminosalicylic acid, 5-ASA), a currently used drug for anti-inflammatory bowel disease, is easily oxidized by HOCl, a strong oxidant generated in gut inflammation, to produce electrophilic quinones. We investigated whether this chemical feature has an implication in the anti-inflammatory pharmacology of 5-ASA. Human colon carcinoma HCT116 cells were treated with HOCl-reacted 5-ASA. Oxidized 5-ASA activated Nrf2 while 5-ASA itself was not effective. Activation of Nrf2 led to induction of hemeoxygenase (OH)-1, an anti-inflammatory enzyme. Western blot analysis of Keap1, a cytosolic repressor of Nrf2, following precipitation of biotin-labeled proteins in cell lysates treated with biotin-tagged 5-ASA, revealed a much greater amount of Keap1 when biotin-tagged 5-ASA was oxidized with HOCl. Precipitation of Keap1 was attenuated markedly by pretreatment with oxidized 5-ASA or a sulfhydryl donor. In addition, treatment with oxidized 5-ASA in cell lysates reduced the Keap1 amount that coimmunoprecipitated with Nrf2. In parallel, rectal administration of 5-ASA increased the level of HO-1 and nuclear Nrf2 in the inflamed colonic tissues, but not in normal colonic tissues. Moreover, oral gavage of sulfasalazine, a colon-specific prodrug of 5-ASA currently used clinically, activated the Nrf2-HO-1 pathway in the colonic tissues where inflammation was in progress, which was not observed when inflammation subsided. Collectively, our data suggest that Nrf2-HO-1 pathway is involved in the anti-inflammatory pharmacology of 5-ASA, which was likely being exerted exclusively in the inflammatory state. | - |
dc.language | English | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.subject | INFLAMMATORY BOWEL DISEASES | - |
dc.subject | EPITHELIAL-CELLS | - |
dc.subject | COLITIS | - |
dc.subject | COLON | - |
dc.subject | EXPRESSION | - |
dc.subject | MECHANISM | - |
dc.subject | MICE | - |
dc.title | Oxidized 5-aminosalicylic acid activates Nrf2-HO-1 pathway by covalently binding to Keap1: Implication in anti-inflammatory actions of 5-aminosalicylic acid | - |
dc.type | Article | - |
dc.identifier.wosid | 000403463500063 | - |
dc.identifier.scopusid | 2-s2.0-85018965632 | - |
dc.type.rims | ART | - |
dc.citation.volume | 108 | - |
dc.citation.beginningpage | 715 | - |
dc.citation.endingpage | 724 | - |
dc.citation.publicationname | FREE RADICAL BIOLOGY AND MEDICINE | - |
dc.identifier.doi | 10.1016/j.freeradbiomed.2017.04.366 | - |
dc.contributor.nonIdAuthor | Kang, Sookjin | - |
dc.contributor.nonIdAuthor | Kim, Wooseong | - |
dc.contributor.nonIdAuthor | Jeong, Seongkeun | - |
dc.contributor.nonIdAuthor | Nam, Joon | - |
dc.contributor.nonIdAuthor | Lee, Sunyoung | - |
dc.contributor.nonIdAuthor | Jung, Yunjin | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Aminosalicylic acid | - |
dc.subject.keywordAuthor | Colitis | - |
dc.subject.keywordAuthor | Nuclear factor-erythroid 2 (NF-E2) p45-related factor 2 | - |
dc.subject.keywordAuthor | Covalent bond | - |
dc.subject.keywordAuthor | Oxidation | - |
dc.subject.keywordPlus | INFLAMMATORY BOWEL DISEASES | - |
dc.subject.keywordPlus | EPITHELIAL-CELLS | - |
dc.subject.keywordPlus | COLITIS | - |
dc.subject.keywordPlus | COLON | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | MICE | - |
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