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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred


SCImago Journal Rank (SJR) 2015: 1.607
Source Normalized Impact per Paper (SNIP) 2015: 0.751
Impact per Publication (IPP) 2015: 2.609

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1437-4315
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Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents

Ying Hu1 / Sabine Urig2 / Sasa Koncarevic3 / Xinjiang Wu4 / Marina Fischer5 / Stefan Rahlfs6 / Volker Mersch-Sundermann7 / Katja Becker8

1Interdisciplinary Research Center, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany

2Interdisciplinary Research Center, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany

3Interdisciplinary Research Center, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany

4Faculty of Medicine, Institute of Indoor and Environmental Toxicology, University Hospital of Giessen and Marburg, Aulweg 123, D-35385 Giessen, Germany

5Interdisciplinary Research Center, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany

6Interdisciplinary Research Center, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany

7Faculty of Medicine, Institute of Indoor and Environmental Toxicology, University Hospital of Giessen and Marburg, Aulweg 123, D-35385 Giessen, Germany

8Interdisciplinary Research Center, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany

Corresponding author

Citation Information: Biological Chemistry. Volume 388, Issue 10, Pages 1069–1081, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: https://doi.org/10.1515/BC.2007.135, October 2007

Publication History

Received:
2007-04-04
Accepted:
2007-07-22
Published Online:
2007-10-16

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 (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.

Keywords: A549 cells; allyl sulfides; enzyme inhibition; isothiocyanates; redox networks; transcript levels

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