Interplay between the chalcone cardamonin and selenium in the biosynthesis of Nrf2-regulated antioxidant enzymes in intestinal Caco-2 cells
| Autor: | Holger Steinbrenner, Mustafa Micoogullari, Helmut Sies, Silke De Spirt, Wilhelm Stahl, Carina Wehrend, Anna Eckers |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Chalcone Thioredoxin Reductase 1 GPX2 Antioxidant NF-E2-Related Factor 2 Phosphorylase Kinase medicine.medical_treatment Biology digestive system Biochemistry 03 medical and health sciences chemistry.chemical_compound Selenium 0302 clinical medicine Chalcones Glutathione Peroxidase GPX1 Intestinal mucosa Physiology (medical) medicine Humans Intestinal Mucosa Selenoproteins chemistry.chemical_classification Glutathione Peroxidase Glutathione peroxidase respiratory system Cytoprotection Heme oxygenase 030104 developmental biology chemistry 030220 oncology & carcinogenesis Enzyme Induction Protein Biosynthesis Selenoprotein Caco-2 Cells Heme Oxygenase-1 |
| Zdroj: | Free radical biologymedicine. 91 |
| ISSN: | 1873-4596 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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