title: 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.
authors: National Institute of Nutrition and Seafood Research, NO-5817 Bergen, Norway; Department of Biology, University of Bergen, 5020 Bergen, Norway. Electronic address: spe@nifes.no.
authors: S
authors: S
authors: Penglase
authors: National Institute of Nutrition and Seafood Research, NO-5817 Bergen, Norway.
authors: K
authors: K
authors: Hamre
authors: National Institute of Nutrition and Seafood Research, NO-5817 Bergen, Norway.
authors: S
authors: S
authors: Ellingsen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015536:Down-Regulation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007453:Iodide Peroxidase / Q000235:genetics; D051150:Methionine Sulfoxide Reductases / Q000235:genetics; D008767:Methylmercury Compounds / Q000494:pharmacology*; D010770:Phosphotransferases / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D012643:Selenium / Q000494:pharmacology*; D051140:Selenoproteins / Q000235:genetics*; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics; D014874:Water Pollutants, Chemical; D015027:Zebrafish
chemical_list: D000975:Antioxidants; D008767:Methylmercury Compounds; D012333:RNA, Messenger; D051140:Selenoproteins; D014874:Water Pollutants, Chemical; D007453:Iodide Peroxidase; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D010770:Phosphotransferases; C062762:selenophosphate synthetase; D012643:Selenium
keywords: Free radicals; Methylmercury; Selenium; Selenoprotein; Toxicity; Zebrafish