Acknowledgments The authors thank Judy Benson for copyediting the manuscript. Conflict of interest None declared.
Selenium (Se) is an essential micronutrient that is incorporated into antioxidant Ponatinib mw enzymes. Se is unique among trace elements because it is covalently incorporated into proteins as a noncanonical amino acid, selenocysteine (Sec). Biosynthesis and integration of Sec in polypeptides is distinctive
because the residue is specified by a UGA codon, which is typically a stop codon. Recoding the UGA codon Inhibitors,research,lifescience,medical for Sec incorporation requires an mRNA that contains a Sec insertion sequence (SECIS), a tRNA that recognizes UGA, and several specific proteins beyond the conventional translation machinery (reviewed in Bellinger et al. 2009). The 25 primate, and 24 murine, Sec-containing selenoproteins Inhibitors,research,lifescience,medical identified to date include the functionally characterized glutathione peroxidase (GPX), thioredoxin reductase, and iodothyronine deiodinase enzyme families. Selenoprotein W (Sepw1) is the smallest mammalian selenoprotein and is one of the most widely distributed selenoproteins across species in all domains of life (Zhang and Gladyshev 2008; Lobanov et al. 2009). Sepw1
was initially identified by its absence in muscle of myopathic lambs suffering White Muscle disease, and was later purified and cloned (Vendeland et al. 1993, Inhibitors,research,lifescience,medical 1995; Whanger 2000). White muscle disease is a Se-responsive muscular dystrophy syndrome Inhibitors,research,lifescience,medical in sheep and cattle that is characterized by pale and dry muscle, with longitudinal striations or chalky whiteness due to abnormal calcium deposition. Leg muscles typically degenerate first, but all muscles, including cardiac, can be affected. In addition to muscle and proliferating myoblasts, mammalian Sepw1 is highly expressed in the developing and adult brain
(Gu et al. 2000; Loflin et al. 2006). Unlike in muscle, dietary Se deficiency does not reduce Sepw1 levels in sheep or rat brain, despite reducing brain Se concentration and GPX activity (Sun et al. 2001; Whanger 2001). Selenoprotein P (Sepp1) maintains stable selenoprotein Inhibitors,research,lifescience,medical expression in the brain under Se deficiency, Vasopressin Receptor and mice lacking Sepp1 have greatly reduced levels of Sepw1 mRNA and protein in the brain (Hoffmann et al. 2007). Feeding a Se-deficient diet to mice lacking Sec lyase (Scly) also reduces Sepw1 protein in the brain (Raman et al. 2012). These results suggest that preferential retention of Sepw1 in brain during dietary Se deficiency is maintained by Sepp1 and Scly. Regional analysis of Sepw1 mRNA expression in the brains of mice indicates presence in neurons, with high expression in >90% of brain regions (Zhang et al. 2008). However, the expression, regulation, and function of Sepw1 in the brain are largely unknown. Like most selenoproteins, Sepw1 is expected to be involved in oxidation–reduction (redox) reactions.