The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity

被引:57
作者
Boots, AW [1 ]
Balk, JM [1 ]
Bast, A [1 ]
Haenen, GRMM [1 ]
机构
[1] Univ Maastricht, Fac Med, Dept Pharmacol & Toxicol, NL-6200 MD Maastricht, Netherlands
关键词
flavonoids; quercetin; quinone; glutathionyl-quercetin adduct; reversibility; toxicity; dihydrolipoic acid;
D O I
10.1016/j.bbrc.2005.10.031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:923 / 929
页数:7
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