Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products
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Michael Haack
Abstract
Glucosinolates (GLSs) present in Brassica vegetables serve as precursors for biologically active metabolites, which are released by myrosinase and induce phase 2 enzymes via the activation of Nrf2. Thus, GLSs are generally considered beneficial. The pattern of GLSs in plants is various, and contents of individual GLSs change with growth phase and culture conditions. Whereas some GLSs, for example, glucoraphanin (GRA), the precursor of sulforaphane (SFN), are intensively studied, functions of others such as the indole GLS neoglucobrassicin (nGBS) are rather unknown as are functions of combinations thereof. We therefore investigated myrosinase-treated GRA, nGBS and synthetic SFN for their ability to induce NAD(P)H:quinone oxidoreductase 1 (NQO1) as typical phase 2 enzyme, and glutathione peroxidase 2 (GPx2) as novel Nrf2 target in HepG2 cells. Breakdown products of nGBS potently inhibit both GRA-mediated stimulation of NQO1 enzyme and Gpx2 promoter activity. Inhibition of promoter activity depends on the presence of an intact xenobiotic responsive element (XRE) and is also observed with benzo[a]pyrene, a typical ligand of the aryl hydrocarbon receptor (AhR), suggesting that suppressive effects of nGBS are mediated via AhR/XRE pathway. Thus, the AhR/XRE pathway can negatively interfere with the Nrf2/ARE pathway which has consequences for dietary recommendations and, therefore, needs further investigation.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Guest Editorial
- Highlight: Xenobiotics and Cell Signaling
- Reviews
- An introduction to the molecular basics of aryl hydrocarbon receptor biology
- Mechanisms and cell signaling in alcoholic liver disease
- Superoxide anion and hydrogen peroxide-induced signaling and damage in angiotensin II and aldosterone action
- Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products
- Cadmium ions promote monocytic differentiation of human leukemia HL-60 cells treated with 1α,25-dihydroxyvitamin D3
- Zonation of heme synthesis enzymes in mouse liver and their regulation by β-catenin and Ha-ras
- The C2-streptavidin delivery system promotes the uptake of biotinylated molecules in macrophages and T-leukemia cells
- Short Communications
- c-Src-mediated activation of Erk1/2 is a reaction of epithelial cells to carbon nanoparticle treatment and may be a target for a molecular preventive strategy
- Loss of gap junctional intercellular communication in rat lung epithelial cells exposed to carbon or silica-based nanoparticles
- Review
- Lipoprotein receptors – an evolutionarily ancient multifunctional receptor family
