Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system
Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system
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DOI：
10.1016/j.bbrc.2007.05.139
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发表时间：
2007-08-03
影响因子：
3.1
通讯作者：
Kwon, Ho Jeong
中科院分区：
文献类型：
--
作者：
Choi, Hee Shim;Shim, Joong Sup;Kwon, Ho Jeong
硫氧还蛋白氧化还原系统被认为是一种细胞内抗氧化防御系统，利用NADPH的电子减少细胞氧化应激。通过针对该系统的高含量小分子筛选，鉴定出真菌代谢物胶质毒素是一种活性化合物。胶质毒素能有效加速NADPH氧化和减少H2O2。该化合物在体外通过取代过氧化物氧还蛋白的功能将H2O2还原为H2O，降低HeLa细胞内H2O2水平。胶质毒素的抗氧化活性进一步证实了h2o2介导的血管生成细胞表型。在纳摩尔范围内抑制内皮细胞的增殖。此外，h2o2诱导的小管形成和细胞的侵袭被胶质毒素阻断。这些结果表明，胶质毒素是一种新的靶向硫氧还蛋白氧化还原系统的小分子。(c) 2007爱思唯尔公司版权所有。
Thioredoxin redox system has been implicated as an intracellular anti-oxidant defense system leading to reduction of cellular oxidative stresses utilizing electrons from NADPH. From high content screening of small molecules targeting the system, gliotoxin, a fungal metabolite, was identified as an active compound. Gliotoxin potently accelerates NADPH oxidation and reduces H2O2. The compound reduces H2O2 to H2O by replacing the function of peroxiredoxin in vitro and decreases intracellular level of H2O2 in HeLa cells. The anti-oxidant activity of gliotoxin was further validated H2O2-mediated cellular phenotype of angiogenesis. The proliferation of endothelial cells was inhibited by the compound at nanomolar range. In addition, H2O2-induced tube formation and invasion of the cells were blocked by gliotoxin. Together, these results demonstrate that gliotoxin is a new small molecule targeting thioredoxin redox system. (c) 2007 Elsevier Inc. All rights reserved.