Selenium prevents downregulation of antioxidant selenoprotein genes by methylmercury

Abstract

Selenium (Se) is an essential nutrient required by Se-dependent proteins, termed selenoproteins. The selenoprotein family is small but diverse and includes key proteins in antioxidant, redox signaling, thyroid hormone metabolism, and protein folding pathways. Methylmercury (MeHg) is a toxic environmental contaminant that affects seafood safety. Selenium can reduce MeHg toxicity, but it is unclear how selenoproteins are affected in this interaction. In this study we explored how Se and MeHg interact to affect the mRNA expression of selenoprotein genes in whole zebrafish (Danio rerio) embryos. Embryos were obtained from adult zebrafish fed MeHg with or without elevated Se in a 2×2 factorial design. The embryo mRNA levels of 30 selenoprotein genes were then measured. These genes cover most of the selenoprotein families, including members of the glutathione peroxidase (GPX), thioredoxin reductase, iodothyronine deiodinase, and methionine sulfoxide reductase families, along with selenophosphate synthetase 2 and selenoproteins H, J-P, T, W, sep15, fep15, and fam213aa. GPX enzyme activity and larval locomotor activity were also measured. We found that around one-quarter of the selenoprotein genes were downregulated by elevated MeHg. These downregulated genes were dominated by selenoproteins from antioxidant pathways that are also susceptible to Se-deficiency-induced downregulation. MeHg also decreased GPX activity and induced larval hypoactivity. Elevated Se partially prevented MeHg-induced disruption of selenoprotein gene mRNA levels, GPX activity, and larval locomotor activity. Overall, the MeHg-induced downregulation and subsequent rescue by elevated Se levels of selenogenes regulated by Se status suggest that Se deficiency is a contributing factor to MeHg toxicity.

Methylmercury Induced Neurotoxicity and the Influence of Selenium in the Brains of Adult Zebrafish (Danio rerio)

“…Additionally, cadmium-induced cell death, while not inhibited, was also significantly reduced in RICTOR-silenced PC12 cells [31], highlighting the importance of this regulator in the context of heavy metal toxicity in the brain. In addition to rapamycin, selenium was also reported to antagonise cadmium induced toxicity; most likely also through effects on the important balance between pro-oxidant toxic metals and antioxidant essential elements [33,34,35]. …”

Evaluation of selenium on kidney function following ischemic injury in rats; protective effects and antioxidant activity

“…Se is found in the form of selenocysteine in the active moiety as a consisting component of 25 types of selenoprotein, such as GPx p-selenoprotein (29,30). Se is able of diminishing the production of the oxygen free radicals (31). Se supplement with Na 2 Se 3 can protect the heart of the immature rats from ischemia and reperfusion injury (9).…”

Antagonistic Growth Effects of Mercury and Selenium in Caenorhabditis elegans Are Chemical-Species-Dependent and Do Not Depend on Internal Hg/Se Ratios

“…Antagonism between Hg and Se has been observed previously, with other end-points with many different selenocompounds in a number of ameliorated or partially ameliorated end points including enzyme activity, enzyme expression, and DNA damage. 8, 18, 48 …”

“…However, the same group that reported synergistic effects of reduced reproduction also observed partial mitigation of embryonic selenoprotein gene mRNA levels, GPX activity, and larval locomotion. 18 The mechanisms that underlie greater than additive toxicity are not well-understood.…”

“…14–17 Potential mechanisms for synergism are less clear, but may include altering antioxidant capabilities, thereby promoting a prooxidative environment. 8, 9, 18 …”