Copper interferes with selenoprotein synthesis and activity

Abstract

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.

Ageing-associated effects of a long-term dietary modulation of four trace elements in mice

“…3 F). The serum Cu/Se ratio is another composite biomarker related to the redox status and upon increase indicative for a state of (infectious) disease and poor health in both humans and mice [ [85] , [86] , [87] , [88] ]. The serum Cu/Se ratio was lower in the +TE aa groups in comparison to the -TE and +TE groups, which is plausible as within the +TE aa intervention, mice received increased amounts of Se ( Fig.…”

N-Acetylcysteine as Modulator of the Essential Trace Elements Copper and Zinc

“…For experiments, the cells were seeded for 24 h and accordingly were treated with or without 1 mM NAC (Sigma-Aldrich) dissolved in culture medium without FCS. In parallel, copper sulfate (CuSO 4 ) (Sigma-Aldrich/Merck) and zinc sulfate (ZnSO 4 ) (Sigma-Aldrich/Merck) were added in a final concentration of 50 µM for 6 h. The concentrations of Cu and Zn were chosen based on previous experiments [ 17 ]. Cells were harvest 30 h after seeding.…”

“…Male C57BL/6Jrj mice were housed on a 12:12 h light:dark schedule with food and tap water ad libitum. The mouse strain was chosen to allow for comparison with previous results [ 17 ]. A commercially available chow diet (V1534, Ssniff, Soest, Germany) with 97 and 8.8 mg/kg Zn and Cu, respectively, was used.…”

The Trace Element Selenium Is Important for Redox Signaling in Phorbol Ester-Differentiated THP-1 Macrophages

“…The SensiFAST™ cDNA Synthesis Kit was used for cDNA transcription. For real-time PCR, cDNA were combined with Master mix (PerfeCTa SYBR Green Supermix, forward and reverse primer (each 250 nM final concentration)) in a 96-well plate as previously described [56]. Primer sequences are given in Table 1.…”