Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents

被引:40
作者
Hu, Ying
Urig, Sabine
Koncarevic, Sasa
Wu, Xinjiang
Fischer, Marina
Rahlfs, Stefan
Mersch-Sundermann, Volker
Becker, Katja
机构
[1] Univ Giessen, Interdisciplinary Res Ctr, D-35392 Giessen, Germany
[2] Univ Hosp Giessen & Marburg, Fac Med, Inst Indoor & Environm Toxicol, D-35385 Giessen, Germany
关键词
A549; cells; allyl sulfides; enzyme inhibition; isothiocyanates; redox networks; transcript levels;
D O I
10.1515/BC.2007.135
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
We studied the effects of sulfur-containing chemopreventive agents, including allyl sulfides and isothiocyanates, on human redox networks. Isothiocyanates inhibited isolated redox-active enzymes in a time- and dose-dependent manner. As shown for the most active compound, benzyl isothiocyanate (BITC), on thioredoxin reductase, the inhibition has an initial competitive part (K-i = 6.1 +/- 1.0 mu m) followed by a time-dependent irreversible inhibition (k(2)=72.8 +/- 25.5 M-1 S-1). Also, glutathione reductase and glutathione S-transferase were irreversibly modified by BITC. Sulforaphane led to irreversible inhibition of the studied redox enzymes, but with 5-10 times lower k(2) values. In contrast, allyl sulfides had only moderate effects on the tested enzymes. However, diallyl disulfide was found to react directly with reduced glutathione (k(2)=100 M-2 S-1). This reaction might contribute to enhanced oxidative stress and the induction of the selenoprotein glutathione peroxidase as determined on activity and transcript levels. All chemopreventive agents tested induced transcript levels of genes associated with cell cycle arrest and apoptosis. This upregulation was accompanied by a dose-dependent decrease in cell number. Our data indicate that modulation of cellular redox networks is likely to contribute to the effects of sulfur-containing chemopreventive agents.
引用
收藏
页码:1069 / 1081
页数:13
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