Peer-Reviewed Journal Details
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Hill, KE, Zhou, JD, Austin, LM, Motley, AK, Ham, AJL, Olson, GE, Atkins, JF, Gesteland, RF, Burk, RF;
The Journal of Biological Chemistry
The Selenium-Rich C-Terminal Domain of Mouse Selenoprotein P Is Necessary For The Supply of Selenium to Brain and Testis But Not For The Maintenance of Whole Body Selenium
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Selenoprotein P (Sepp1) has two domains with respect to selenium content: the N-terminal, selenium-poor domain and the C-terminal, selenium-rich domain. To assess domain function, mice with deletion of the C-terminal domain have been produced and compared with Sepp1(-/-) and Sepp1(-)/(-) mice. All mice studied were males fed a semipurified diet with defined selenium content. The Sepp1 protein in the plasma of mice with the C-terminal domain deleted was determined by mass spectrometry to terminate after serine 239 and thus was designated Sepp1 Delta 240 - 361. Plasma Sepp1 and selenium concentrations as well as glutathione peroxidase activity were determined in the three types of mice. Glutathione peroxidase and Sepp1(Delta 240-361) accounted for over 90% of the selenium in the plasma of Sepp1(Delta 240-361) mice. Calculations using results from Sepp1(-/-) mice revealed that Sepp1, with a potential for containing 10 selenocysteine residues, contained an average of 5 selenium atoms per molecule, indicating that shortened and/or selenium-depleted forms of the protein were present in these wild-type mice. Sepp1(Delta 240 - 361) mice had low brain and testis selenium concentrations that were similar to those in Sepp1(-/-) mice but they better maintained their whole body selenium. Sepp1(Delta 240-361) mice had depressed fertility, even when they were fed a high selenium diet, and their spermatozoa were defective and morphologically indistinguishable from those of selenium-deficient mice. Neurological dysfunction and death occurred when Sepp1(Delta 240-361) mice were fed selenium-deficient diet. These phenotypes were similar to those of Sepp1(-/-) mice but had later onset or were less severe. The results of this study demonstrate that the C terminus of Sepp1 is critical for the maintenance of selenium in brain and testis but not for the maintenance of whole body selenium..
DOI 10.1074/jbc.M700436200
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