Disease relevance of SEPW1

• The function of selenoprotein W (Se-W) was investigated by cloning the corresponding cDNA from mouse brain and expressing it in CHO cells and H1299 human lung cancer cells [1].

High impact information on SEPW1

• Surprisingly, we detected selenoproteins in a member of the plant kingdom, Chlamydomonas reinhardtii, and directly identified two of them as phospholipid hydroperoxide glutathione peroxidase and selenoprotein W homologs [2].
• Differential gene expressions of selenoprotein W and uroporphyrinogen decarboxylase, which can be involved in oxidative stress, were also observed [3].
• Selenoprotein W was undetectable in skeletal muscle of rats fed the basal diet, detectable in those fed 0.1 ppm selenium in the diet, and much higher in muscle from rats fed 4 ppm selenium diet [4].
• The resulting polyclonal antibodies were used in Western blots to determine the compartmentation and tissue distribution of selenoprotein W, and to determine the influence of selenium on the levels of this selenoprotein in rat muscle [4].
• Western blots revealed selenoprotein W in muscle, spleen, testis, and brain of rats [4].

Biological context of SEPW1

• Additionally, we have also identified a retroprocessed SEPW1 pseudogene, SEPW1P, which maps to chromosome 1p34-35 [5].
• We have determined that the human SEPW1 (selenoprotein W) gene maps to chromosome 19q13.3, spans approximately 6.3 kb and comprises six exons, in contrast to the previously published five exons [5].
• Effects of Se-depletion on glutathione peroxidase and selenoprotein W gene expression in the colon [6].
• Therefore, we suggest that SeW is the novel molecular target of MeHg in human neuronal cells and down-regulation of this selenoenzyme by MeHg is dependent not on generation of ROS but on depletion of GSH [7].
• Tissue distribution and influence of selenium status on levels of selenoprotein W [4].

Anatomical context of SEPW1

• SEPW1 is expressed in all of the 22 tissues assayed, and shows highest expression in skeletal muscle and heart [5].
• Selenoprotein W exists mainly in cytosol, but very small amounts were associated with membranes [4].
• Overexpression of Se-W markedly reduced the sensitivity of both cell lines to H2O2 cytotoxicity [1].
• Selenoprotein W exhibited an immediate response to oxidative stress in proliferating myoblasts, after exposure to hydrogen peroxide, similar to gluteraldehyde-3-phosphate dehydrogenase [8].
• Selenoprotein W was highly expressed in proliferating myoblasts and less or not in differentiated myotubes [8].

Associations of SEPW1 with chemical compounds

• Purification of selenoprotein W (Se-W) from rat and monkey muscles was shown to exist in multiple forms: with or without reduced glutathione and/or a 41-Da moiety (identity still unknown) [9].
• Selenoprotein W as molecular target of methylmercury in human neuronal cells is down-regulated by GSH depletion [7].
• Selenoprotein P, a glycoprotein that contains 10 selenocysteine residues per 43 kDa polypeptide and selenoprotein W, a 10 kDa muscle protein, are unidentified as to function [10].
• Expression of Se-W mutants in which selenocysteine-13 or cysteine-37 was replaced by serine did not confer resistance to H2O2, implicating these residues in the antioxidant activity of Se-W in vivo [1].
• Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism [11].

Other interactions of SEPW1

• Although the metabolic function of Se-W is unknown, preliminary data suggest that it has an antioxidant function [9].
• Selenoprotein P, selenoprotein W, a 15-kDa selenoprotein, an 18-kDa selenoprotein, and several selenoproteins identified in silico from nucleotide sequence databases were found to contain selenocysteine but their functions are not known [12].
• Recent studies in cell culture and gene knockout models support a function for selenoprotein P in delivery of selenium to the brain. mRNAs for other selenoproteins, including selenoprotein W, thioredoxin reductases, 15-kDa selenoprotein and type 2 iodothyronine deiodinase, are also detected in the brain [13].
• Selenoproteins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase [14].

Analytical, diagnostic and therapeutic context of SEPW1

• Using real-time RT PCR, the influence of selenium (Se) and glutathione (GSH) on SeW expression was also investigated [7].
• In a species comparison, Western blots indicated the presence of selenoprotein W in muscle of rabbits, sheep, and cattle [4].
• Northern blots using a human selenoprotein W cDNA probe indicated that mRNA levels were highest in monkey skeletal muscle and heart (2-2.5 fold greater than in liver), which is similar to the pattern found with a human multiple tissue Northern blot [15].

References