The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity
The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity
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DOI：
10.1016/j.bbrc.2005.10.031
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发表时间：
2005-12-16
影响因子：
3.1
通讯作者：
Haenen, GRMM
中科院分区：
文献类型：
--
作者：
Boots, AW;Balk, JM;Haenen, GRMM
槲皮素是最重要的膳食抗氧化剂之一。在其抗氧化活性期间，槲皮素被氧化成其邻醌/醌甲基化物QQ。QQ是有毒的，因为它与硫醇，例如，proteins.在细胞中，QQ最初会与谷胱甘肽（GSH）形成加合物，产生GSQ。我们发现GSQ不稳定;它连续解离为GSH和QQ，半衰期为2分钟。令人惊讶的是，GSQ与2-巯基乙醇（MSH）（一种反应性低得多的硫醇）一起孵育，导致GSQ转化为MSH加合物MSQ。预期GSQ类似地转化为相对稳定的蛋白质硫醇-槲皮素加合物。与二硫醇二氢硫辛酸（L（SH）（2）），槲皮素形成了GSQ。这些结果表明，GSQ作为运输和储存QQ。这样，QQ最初高度集中的毒性被GSQ的形成分散，GSQ最终将QQ诱导的毒性扩散，甚至可能扩散到细胞上。(c)2005年爱思唯尔公司All rights reserved.
Quercetin is one of the most prominent dietary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its o-quinone/quinone methide QQ. QQ is toxic since it instantaneously reacts with thiols of, e.g., proteins. In cells, QQ will initially form an adduct with glutathione (GSH), giving GSQ. We have found that GSQ is not stable; it dissociates continuously into GSH and QQ with a half life of 2 min. Surprisingly, GSQ incubated with 2-mercapto -ethanol (MSH), a far less reactive thiol, results in the conversion of GSQ into the MSH-adduct MSQ. A similar conversion of GSQ into relatively stable protein thiol-quercetin adducts is expected. With the dithiol dihydrolipoic acid (L(SH)(2)), quercetin is formed out of GSQ. These results indicate that GSQ acts as transport and storage of QQ. In that way, the initially highly focussed toxicity of QQ is dispersed by the formation of GSQ that finally spreads QQ-induced toxicity, probably even over cells. (c) 2005 Elsevier Inc. All rights reserved.