Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
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Ying Hu
Abstract
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 (Ki=6.1±1.0 μM) followed by a time-dependent irreversible inhibition (k2=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 k2 values. In contrast, allyl sulfides had only moderate effects on the tested enzymes. However, diallyl disulfide was found to react directly with reduced glutathione (k2=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.
©2007 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Selenoproteins – biochemistry and clinical relevance
- Selenium in mammalian spermiogenesis
- Selenium in chemistry and biochemistry in comparison to sulfur
- Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function
- Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals
- Activation of the glutathione peroxidase 2 (GPx2) promoter by β-catenin
- Effect of age on sexually dimorphic selenoprotein expression in mice
- Post-translational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells
- Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3
- Towards understanding selenocysteine incorporation into bacterial proteins
- Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
- B- and T-cell-specific inactivation of thioredoxin reductase 2 does not impair lymphocyte development and maintenance
- Effect of selenium on thioredoxin reductase activity in Txnrd1 or Txnrd2 hemizygous mice
- Influence of pH and flanking serine on the redox potential of S-S and S-Se bridges of Cys-Cys and Cys-Sec peptides
- An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors
- Glucocorticoid receptor-mediated expression of kallikrein 10 in human breast cancer cell lines
