Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 371882
Title Shifted concentration dependency of EpRE- and XRE-mediated gene expression points at monofunctional EpRE-mediated induction by flavonoids at physiologically relevant concentrations
Author(s) Lee, Y.Y.; Borg, S. ter; Berkel, W.J.H. van; Rietjens, I.M.C.M.; Aarts, J.M.M.J.G.
Source Toxicology in Vitro 22 (2008)4. - ISSN 0887-2333 - p. 921 - 926.
Department(s) Biochemistry
Sub-department of Toxicology
Publication type Refereed Article in a scientific journal
Publication year 2008
Keyword(s) aryl-hydrocarbon receptor - drug-metabolizing-enzymes - ah-receptor - nad(p)h-quinone oxidoreductase - transcriptional regulation - dietary polyphenols - quinone reductase - signaling pathway - cell-lines - in-vitro
Abstract Flavonoids are important bioactive compounds, omnipresent in the human diet, and are reported to be bifunctional inducers. These phytochemicals are able to induce xenobiotic-responsive element (XRE)- and electrophile-responsive element (EpRE)-mediated gene expression, resulting in the induction of biotransformation enzymes. To test whether flavonoid-induced EpRE-mediated gene expression could be the result of upstream XRE-mediated gene expression, several flavonoids were tested for their ability to induce XRE- and EpRE-mediated gene expression using two stably transfected reporter gene cell lines constructed in the same mouse Hepa-1c1c7 hepatoma background. Although classified as bifunctional inducers, all flavonoids were found to induce EpRE- and XRE-mediated gene expression in a different concentration range, which presents an issue not considered by the current definition of a bifunctional inducer. At physiological relevant concentrations, the induction of gene expression via the EpRE transcriptional enhancer element is dominant, leading in particular to elevated levels of EpRE-regulated detoxifying enzymes. Furthermore, these results strongly suggest that EpRE-mediated gene expression induced by flavonoids is not a downstream reaction of XRE-mediated gene expression.
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