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

Abstract

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.

Copper interferes with selenoprotein synthesis and activity

“…6 A) and total Gpx activity ( Fig. 7 A) were downregulated to 14% or 4% in relation to the +Se group, which is in line with previous feeding experiments using the Se-deficient torula yeast diet [ 37 , 38 ]. However, the Cu status was affected only marginally by our intervention, because the low Cu content of the diet was obviously enough to maintain Cu homeostasis efficiently.…”

Postprandial Metabolic Response to Rapeseed Protein in Healthy Subjects

“…Zinc and copper ( Table 3 ) were analyzed by ICP-MS/MS. Therefore, samples were pretreated with HNO 3 (65% suprapur) and H 2 O 2 (30% suprapur) and microwave digested (200 °C, 20 min) [ 38 ]. The crude fat and crude fiber levels of the protein isolates were analyzed using official methods [ 39 , 40 ].…”

Effects of a Cumulative, Suboptimal Supply of Multiple Trace Elements in Mice: Trace Element Status, Genomic Stability, Inflammation, and Epigenetics

“…20-50 mg of pulverized samples were applied for acidic microwave-assisted digestion as described in detail by Schwarz and colleagues. [26] Briefly, tissue and feces samples were digested in a microwave digestion system (CEM-Mars 6 or CEM-Discover SP-D, respectively, Kamp-Lintfort, Germany) with HNO 3 (65% Suprapur, Merck), H 2 O 2 (30%, Merck) as well as internal and isotope-dilution standards in PTFE or glass microwave vessels. Subsequently, tissue samples were diluted 1:4 and feces samples were diluted 1:10, resulting in a final concentration of 2.93% HNO 3 .…”

“…Glutathione Peroxidase (Gpx) activity was assessed as previously described. [26] Briefly, about 35 mg of frozen liver were homogenized in TRIS buffer and centrifuged to remove tissue debris. Protein concentrations of resulting protein solutions were determined by Bradford assay (Bio-Rad, Munich, Germany) and Gpx activity was analyzed via an NADPH-consuming glutathione reductase coupled assay using H 2 O 2 as substrate.…”

“…Protein concentrations of resulting protein solutions were determined by Bradford assay (Bio-Rad, Munich, Germany) and Gpx activity was analyzed via an NADPH-consuming glutathione reductase coupled assay using H 2 O 2 as substrate. [26,29] www.advancedsciencenews.com www.mnf-journal.com…”