Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
| Autor: | Xin-jiang Wu, Ying Hu, Katja Becker, Stefan Rahlfs, Volker Mersch-Sundermann, Marina Fischer, Sabine Urig, Sasa Koncarevic |
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| Rok vydání: | 2007 |
| Předmět: |
4-Acetamido-4'-isothiocyanatostilbene-2
2'-disulfonic Acid Thioredoxin-Disulfide Reductase GPX3 Thioredoxin reductase Clinical Biochemistry Glutathione reductase Allyl compound Biochemistry chemistry.chemical_compound Thioredoxins Isothiocyanates Glutaredoxin Cell Line Tumor Anticarcinogenic Agents Humans Disulfides Molecular Biology Cell Proliferation Glutathione Transferase chemistry.chemical_classification Glutathione Peroxidase Dose-Response Relationship Drug Sulfur Compounds Glutathione peroxidase Cell Cycle Glutathione Up-Regulation Allyl Compounds chemistry Thioredoxin Oxidation-Reduction |
| Zdroj: | Biological chemistry. 388(10) |
| ISSN: | 1431-6730 |
| Popis: | 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 μM) 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. |
| Databáze: | OpenAIRE |
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