title: Interplay between the chalcone cardamonin and selenium in the biosynthesis of Nrf2-regulated antioxidant enzymes in intestinal Caco-2 cells.
abstract: Selenoenzymes and nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated phase II enzymes comprise key components of the cellular redox and antioxidant systems, which show multiple interrelations. Deficiency of the micronutrient selenium (Se) and impaired biosynthesis of selenoproteins have been reported to result in induction of Nrf2 target genes. Conversely, transcription of the selenoenzymes glutathione peroxidase 2 (GPx2) and thioredoxin reductase 1 (TrxR1) is up-regulated upon Nrf2 activation. Here, we have studied the interplay between Se and the secondary plant metabolite cardamonin, an Nrf2-activating chalcone, in the regulation of Nrf2-controlled antioxidant enzymes. Se-deficient and Se-repleted (sodium selenite-supplemented) human intestinal Caco-2 cells were exposed to cardamonin. Uptake of cardamonin by the Caco-2 cells was independent of their Se status. Cardamonin strongly induced gene expression of GPx2 and TrxR1. However, cardamonin treatment did not result in elevated GPx or TrxR activity and protein levels, possibly relating to a concomitant down-regulation of O-phosphoseryl-tRNA(Sec) kinase (PSTK), an enzyme involved in translation of selenoprotein mRNAs. On the other hand, induction of the Nrf2-regulated enzyme heme oxygenase 1 (HO-1) by cardamonin was diminished in Se-replete compared to Se-deficient cells. Our findings suggest that cardamonin interferes with the biosynthesis of Nrf2-regulated selenoenzymes, in contrast to the Nrf2-activating isothiocyanate compound sulforaphane, which has been shown earlier to synergize with Se-mediated cytoprotection. Conversely, the cellular Se status apparently affects the cardamonin-mediated induction of non-selenoprotein antioxidant enzymes such as HO-1.
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: De Spirt
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Eckers
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Wehrend
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Micoogullari
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Stahl
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute of Nutrition, Department of Nutrigenomics, Friedrich-Schiller-University, Jena, Germany. Electronic address: Holger.Steinbrenner@uni-jena.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Steinbrenner
mesh_terms: D018938:Caco-2 Cells; D047188:Chalcones / Q000378:metabolism / Q000494:pharmacology*; D004790:Enzyme Induction; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010764:Phosphorylase Kinase / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012643:Selenium / Q000494:pharmacology*; D051140:Selenoproteins / Q000096:biosynthesis / Q000235:genetics; D054481:Thioredoxin Reductase 1 / Q000096:biosynthesis* / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1
chemical_list: D047188:Chalcones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D051140:Selenoproteins; C117436:GPX2 protein, human; D005979:Glutathione Peroxidase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D010764:Phosphorylase Kinase; D012643:Selenium; C436747:cardamonin; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
keywords: Antioxidant protection; Flavonoid; Intestine; Phytochemical; Selenoprotein