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

We studied the effects of sulfur-containing chemopreventive agents, including allyl sulfides and isothiocyanates, on human redox networks

Ying Hu; Sabine Urig; Sasa Koncarevic; Xinjiang Wu; Marina Fischer; Stefan Rahlfs; Volker Mersch-Sundermann; Katja Becker

2007

Scholarcy highlights

  • Occurring allyl sulfides and isothiocyanates have been confirmed to act as chemopreventive agents and are abundant in daily-consumed vegetables and traditional herbal medicine
  • We studied the effects of sulfur-containing chemopreventive agents, including allyl sulfides and isothiocyanates, on human redox networks
  • The inhibitory effects of sulfur-containing compounds on the activity of isolated human thioredoxin reductase, Glutathione reductase and glutathione S-transferase were determined as described in the material and methods section
  • The greatest inhibitory effect was observed for the reaction of diallyl disulfide with hTrxR, which led to 50% enzyme inhibition in the DTNB assay after 30 min preincubation at a concentration of 380"50 mM
  • A disturbed redox equilibrium leads to modulation of redox sensitive transcription factors like nuclear factor E2-related factor 2, activator protein 1 and nuclear factor-kB that sense and transduce changes in the cellular redox status and subsequently modulate gene expression responses
  • The background reaction, which was regularly less than 10% of the TrxR catalyzed reaction, was subtracted in each assay
  • As the induction of cell cycle arrest and/or apoptosis are among the most attractive discussed mechanisms for the preventive action of isothiocyanates and allyl sulfides, we studied changes on the transcriptional level of genes connected to these cellular events
  • For analysis of irreversible inhibition, hTrxR or hGR were incubated with 100 mM benzyl isothiocyanate in the presence or absence of 100 mM NADPH for 30 min and their residual activity was determined in the Trx-reducing assay and the GSSG-reducing assay, respectively, in comparison with a control sample

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