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Open AccessArticle

Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper

by 1,2,†, 1,2,3,4,†, 2,4, 2,4 and 1,2,*
Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany
TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, D-13353 Potsdam-Berlin-Jena, Germany
German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
Author to whom correspondence should be addressed.
These authors equally contributed to the manuscript.
Nutrients 2019, 11(9), 2112;
Received: 10 July 2019 / Revised: 19 August 2019 / Accepted: 23 August 2019 / Published: 5 September 2019
(This article belongs to the Special Issue Dietary Trace Minerals)
Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice. View Full-Text
Keywords: Nrf2; selenium; iron; copper; zinc; homeostasis Nrf2; selenium; iron; copper; zinc; homeostasis
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MDPI and ACS Style

Schwarz, M.; Lossow, K.; Kopp, J.F.; Schwerdtle, T.; Kipp, A.P. Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper. Nutrients 2019, 11, 2112.

AMA Style

Schwarz M, Lossow K, Kopp JF, Schwerdtle T, Kipp AP. Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper. Nutrients. 2019; 11(9):2112.

Chicago/Turabian Style

Schwarz, Maria; Lossow, Kristina; Kopp, Johannes F.; Schwerdtle, Tanja; Kipp, Anna P. 2019. "Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper" Nutrients 11, no. 9: 2112.

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