Graduate Thesis Or Dissertation
 

Selenoprotein W : distribution and function in rat tissue and cultured cells

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  • The objective of this study was to further determine the distribution of selenoprotein W (SeW) in tissues from rats and sheep fed different selenium levels and to search for the possible functions of this protein. In the rat study a total of 28 rat tissues were examined and SeW was found in all of the tissues except for liver, thyroid, pancreas, pituitary and eyes regardless of the level of Se fed. SeW was not detected in heart, lungs, prostate, esophagus, small intestine, tongue, skin diaphragm and skeletal muscle from selenium deficient rats, but was present in these tissues when the two higher levels of selenium (0.1 and 4.0 mg/kg) were fed. SeW has the highest expression in muscle, brain, testis and spleen when selenium is adequate. Interestingly, selenium deficiency resulted in undetectable SeW levels in heart and muscle from deficient sheep and rats, but the content in brain was unaffected by selenium status. Second generation selenium depleted and repleted rats indicated that the expression of SeW in cortex and cerebellum was not significantly affected by selenium, but selenium increased its levels in thalamus. Cortex had the highest SeW expression among the three parts of the rat brain. SeW levels in muscle, spleen, skin and testis were undetectable in weanling rats, but became detectable after 6 weeks of selenium repletion. Studies with various brain cell cultures indicated that Se appears to be metabolized differently by different brain cell types. As demonstrated in neuroblastoma and glial cells, glutathione peroxidase (GPX) activity decreased at a faster rate than SeW with neuroblastoma cells whereas SeW decreased at a faster rate than GPX activity in glial cells when selenium was removed from the media. Since other work showed that glutathione was bound to SeW, it was speculated that it has antioxidant function similar to other selenoproteins. SeW overexpressed and underexpressed cell lines were established by DNA recombinant techniques. There was a greater survival rate of overexpressed cells when incubated with 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) than control cells, suggesting SeW possibly has an antioxidant function.
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