Copper interferes with selenoprotein synthesis and activity.

Autor: Schwarz M; Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, 07743, Germany; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany., Lossow K; Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, 07743, Germany; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany; German Institute of Human Nutrition, Nuthetal, 14558, Germany., Schirl K; Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, 07743, Germany., Hackler J; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany; Institute for Experimental Endocrinology, Charité - University Medical School Berlin, Berlin, 13353, Germany., Renko K; Institute for Experimental Endocrinology, Charité - University Medical School Berlin, Berlin, 13353, Germany; German Federal Institute for Risk Assessment (BfR), Berlin, Germany., Kopp JF; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany; Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Nuthetal, 14558, Germany., Schwerdtle T; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany; German Federal Institute for Risk Assessment (BfR), Berlin, Germany; Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Nuthetal, 14558, Germany., Schomburg L; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany; Institute for Experimental Endocrinology, Charité - University Medical School Berlin, Berlin, 13353, Germany., Kipp AP; Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, 07743, Germany; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany. Electronic address: anna.kipp@uni-jena.de.
Jazyk: angličtina
Zdroj: Redox biology [Redox Biol] 2020 Oct; Vol. 37, pp. 101746. Date of Electronic Publication: 2020 Oct 07.
DOI: 10.1016/j.redox.2020.101746
Abstrakt: Selenium and copper are essential trace elements for humans, needed for the biosynthesis of enzymes contributing to redox homeostasis and redox-dependent signaling pathways. Selenium is incorporated as selenocysteine into the active site of redox-relevant selenoproteins including glutathione peroxidases (GPX) and thioredoxin reductases (TXNRD). Copper-dependent enzymes mediate electron transfer and other redox reactions. As selenoprotein expression can be modulated e.g. by H 2 O 2 , we tested the hypothesis that copper status affects selenoprotein expression. To this end, hepatocarcinoma HepG2 cells and mice were exposed to a variable copper and selenium supply in a physiologically relevant concentration range, and transcript and protein expression as well as GPX and TXNRD activities were compared. Copper suppressed selenoprotein mRNA levels of GPX1 and SELENOW, downregulated GPX and TXNRD activities and decreased UGA recoding efficiency in reporter cells. The interfering effects were successfully suppressed by applying the copper chelators bathocuproinedisulfonic acid or tetrathiomolybdate. In mice, a decreased copper supply moderately decreased the copper status and negatively affected hepatic TXNRD activity. We conclude that there is a hitherto unknown interrelationship between copper and selenium status, and that copper negatively affects selenoprotein expression and activity most probably via limiting UGA recoding. This interference may be of physiological relevance during aging, where a particular shift in the selenium to copper ratio has been reported. An increased concentration of copper in face of a downregulated selenoprotein expression may synergize and negatively affect the cellular redox homeostasis contributing to disease processes.
(Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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