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题名: Adenanthin targets proteins involved in the regulation of disulphide bonds
作者: Muchowicz, Angelika1; Firczuk, Malgorzata1; Chlebowska, Justyna1; Nowis, Dominika1, 2; Stachura, Joanna1; Barankiewicz, Joanna1; Trzeciecka, Anna1; Klossowski, Szymon3; Ostaszewski, Ryszard3; Zagozdzon, Radoslaw1; Pu, Jian-Xin4; null(孙汉董)4; Golab, Jakub1, 5
刊名: BIOCHEMICAL PHARMACOLOGY
关键词: Adenanthin ; Cancer ; Peroxiredoxin ; Protein disulphide isomerase ; Thioredoxin
英文摘要: Adenanthin has been recently shown to inhibit the enzymatic activities of peroxiredoxins (Prdx) land II through its functional alpha,beta-unsaturated ketone group serving as a Michael acceptor. A similar group is found in SK053, a compound recently developed by our group to target the thioredoxin-thioredoxin reductase (Trx-TrxR) system. This work provides evidence that next to Prdx I and II adenanthin targets additional proteins including thioredoxin-thioredoxin reductase system as well as protein disulfide isomerase (PDI) that contain a characteristic structural motif, referred to as a thioredoxin fold. Adenanthin inhibits the activity of Trx-TR system and PDI in vitro in the insulin reduction assay and decreases the activity of Trx in cultured cells. Moreover, we identified Trx-1 as an adenanthin binding protein in cells incubated with biotinylated adenanthin as an affinity probe. The results of our studies indicate that adenanthin is a mechanism-selective, rather than an enzyme-specific inhibitor of enzymes containing readily accessible, nucleophilic cysteines. This observation might be of importance in considering potential therapeutic applications of adenanthin to include a range of diseases, where aberrant activity of Prdx, Trx-TrxR and PDI is involved in their pathogenesis. (C) 2014 Elsevier Inc. All rights reserved.
出版日期: 2014-05-15
卷号: 89, 期号:2, 页码:210-216
DOI标识: 10.1016/j.bcp.2014.02.022
语种: 英语
ISSN号: 0006-2952
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/18118
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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作者单位: 1.Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, PL-02097 Warsaw, Poland
2.Med Univ Warsaw, Dept Gen Transplant & Liver Surg, PL-02097 Warsaw, Poland
3.Polish Acad Sci, Inst Organ Chem, PL-01224 Warsaw, Poland
4.Chinese Acad Sci, Kunming Inst Bot, Kunming, Peoples R China
5.Polish Acad Sci, Inst Phys Chem, Dept 3, Warsaw, Poland

Recommended Citation:
Muchowicz,Angelika;Firczuk,Malgorzata;Chlebowska,Justyna;Nowis,Dominika;Stachura,Joanna;Barankiewicz,Joanna;Trzeciecka,Anna;Klossowski,Szymon;Ostaszewski,Ryszard;Zagozdzon,Radoslaw;Pu,Jian-Xin;Sun,Han-Dong;Golab,Jakub.Adenanthin targets proteins involved in the regulation of disulphide bonds,BIOCHEMICAL PHARMACOLOGY,2014,89(2):210-216
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