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. 2003 Mar 1;370(Pt 2):397–402. doi: 10.1042/BJ20021853

Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues.

Lutz Schomburg 1, Ulrich Schweizer 1, Bettina Holtmann 1, Leopold Flohé 1, Michael Sendtner 1, Josef Köhrle 1
PMCID: PMC1223208  PMID: 12521380

Abstract

Selenoprotein P (SePP), the major selenoprotein in plasma, has been implicated in selenium transport, selenium detoxification or antioxidant defence. We generated SePP-knockout mice that were viable, but exhibited reduced growth and developed ataxia. Selenium content was elevated in liver, but low in plasma and other tissues, and selenoenzyme activities changed accordingly. Our data reveal that SePP plays a pivotal role in delivering hepatic selenium to target tissues.

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Selected References

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  1. Arteel G. E., Mostert V., Oubrahim H., Briviba K., Abel J., Sies H. Protection by selenoprotein P in human plasma against peroxynitrite-mediated oxidation and nitration. Biol Chem. 1998 Aug-Sep;379(8-9):1201–1205. [PubMed] [Google Scholar]
  2. Behne D., Hilmert H., Scheid S., Gessner H., Elger W. Evidence for specific selenium target tissues and new biologically important selenoproteins. Biochim Biophys Acta. 1988 Jul 14;966(1):12–21. doi: 10.1016/0304-4165(88)90123-7. [DOI] [PubMed] [Google Scholar]
  3. Bermano G., Arthur J. R., Hesketh J. E. Selective control of cytosolic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase mRNA stability by selenium supply. FEBS Lett. 1996 Jun 3;387(2-3):157–160. doi: 10.1016/0014-5793(96)00493-0. [DOI] [PubMed] [Google Scholar]
  4. Bermano G., Nicol F., Dyer J. A., Sunde R. A., Beckett G. J., Arthur J. R., Hesketh J. E. Tissue-specific regulation of selenoenzyme gene expression during selenium deficiency in rats. Biochem J. 1995 Oct 15;311(Pt 2):425–430. doi: 10.1042/bj3110425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berry Marla J., Martin Glover W., 3rd, Tujebajeva Roza, Grundner-Culemann Elisabeth, Mansell John B., Morozova Nadya, Harney John W. Selenocysteine insertion sequence element characterization and selenoprotein expression. Methods Enzymol. 2002;347:17–24. doi: 10.1016/s0076-6879(02)47004-8. [DOI] [PubMed] [Google Scholar]
  6. Birringer Marc, Pilawa Sandra, Flohé Leopold. Trends in selenium biochemistry. Nat Prod Rep. 2002 Dec;19(6):693–718. doi: 10.1039/b205802m. [DOI] [PubMed] [Google Scholar]
  7. Brigelius-Flohé R., Lötzer K., Maurer S., Schultz M., Leist M. Utilization of selenium from different chemical entities for selenoprotein biosynthesis by mammalian cell lines. Biofactors. 1995;5(3):125–131. [PubMed] [Google Scholar]
  8. Brigelius-Flohé R. Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med. 1999 Nov;27(9-10):951–965. doi: 10.1016/s0891-5849(99)00173-2. [DOI] [PubMed] [Google Scholar]
  9. Burk R. F., Hill K. E. Orphan selenoproteins. Bioessays. 1999 Mar;21(3):231–237. doi: 10.1002/(SICI)1521-1878(199903)21:3<231::AID-BIES7>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  10. Burk R. F., Hill K. E., Read R., Bellew T. Response of rat selenoprotein P to selenium administration and fate of its selenium. Am J Physiol. 1991 Jul;261(1 Pt 1):E26–E30. doi: 10.1152/ajpendo.1991.261.1.E26. [DOI] [PubMed] [Google Scholar]
  11. Bösl M. R., Takaku K., Oshima M., Nishimura S., Taketo M. M. Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene (Trsp). Proc Natl Acad Sci U S A. 1997 May 27;94(11):5531–5534. doi: 10.1073/pnas.94.11.5531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chambers I., Frampton J., Goldfarb P., Affara N., McBain W., Harrison P. R. The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the 'termination' codon, TGA. EMBO J. 1986 Jun;5(6):1221–1227. doi: 10.1002/j.1460-2075.1986.tb04350.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Flohé L., Günzler W. A. Assays of glutathione peroxidase. Methods Enzymol. 1984;105:114–121. doi: 10.1016/s0076-6879(84)05015-1. [DOI] [PubMed] [Google Scholar]
  14. Gomez B., Jr, Tappel A. L. Selenoprotein P receptor from rat. Biochim Biophys Acta. 1989 Feb 13;979(1):20–26. doi: 10.1016/0005-2736(89)90518-x. [DOI] [PubMed] [Google Scholar]
  15. Hatfield Dolph L., Gladyshev Vadim N. How selenium has altered our understanding of the genetic code. Mol Cell Biol. 2002 Jun;22(11):3565–3576. doi: 10.1128/MCB.22.11.3565-3576.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Holmgren A., Björnstedt M. Thioredoxin and thioredoxin reductase. Methods Enzymol. 1995;252:199–208. doi: 10.1016/0076-6879(95)52023-6. [DOI] [PubMed] [Google Scholar]
  17. Köhrl J., Brigelius-Flohé R., Böck A., Gärtner R., Meyer O., Flohé L. Selenium in biology: facts and medical perspectives. Biol Chem. 2000 Sep-Oct;381(9-10):849–864. doi: 10.1515/BC.2000.107. [DOI] [PubMed] [Google Scholar]
  18. Ma Shuguang, Hill Kristina E., Caprioli Richard M., Burk Raymond F. Mass spectrometric characterization of full-length rat selenoprotein P and three isoforms shortened at the C terminus. Evidence that three UGA codons in the mRNA open reading frame have alternative functions of specifying selenocysteine insertion or translation termination. J Biol Chem. 2002 Jan 30;277(15):12749–12754. doi: 10.1074/jbc.M111462200. [DOI] [PubMed] [Google Scholar]
  19. Motsenbocker M. A., Tappel A. L. A selenocysteine-containing selenium-transport protein in rat plasma. Biochim Biophys Acta. 1982 Oct 28;719(1):147–153. doi: 10.1016/0304-4165(82)90318-x. [DOI] [PubMed] [Google Scholar]
  20. Mustacich D., Powis G. Thioredoxin reductase. Biochem J. 2000 Feb 15;346(Pt 1):1–8. [PMC free article] [PubMed] [Google Scholar]
  21. Park Y. C., Whanger P. D. Toxicity, metabolism and absorption of selenite by isolated rat hepatocytes. Toxicology. 1995 Jun 26;100(1-3):151–162. doi: 10.1016/0300-483x(95)03080-y. [DOI] [PubMed] [Google Scholar]
  22. Saito Y., Hayashi T., Tanaka A., Watanabe Y., Suzuki M., Saito E., Takahashi K. Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein p. J Biol Chem. 1999 Jan 29;274(5):2866–2871. doi: 10.1074/jbc.274.5.2866. [DOI] [PubMed] [Google Scholar]
  23. Saito Yoshiro, Takahashi Kazuhiko. Characterization of selenoprotein P as a selenium supply protein. Eur J Biochem. 2002 Nov;269(22):5746–5751. doi: 10.1046/j.1432-1033.2002.03298.x. [DOI] [PubMed] [Google Scholar]
  24. Savaskan Nicolai E., Bräuer Anja U., Kühbacher Markus, Eyüpoglu Ilker Y., Kyriakopoulos Antonios, Ninnemann Olaf, Behne Dietrich, Nitsch Robert. Selenium deficiency increases susceptibility to glutamate-induced excitotoxicity. FASEB J. 2002 Nov 1;17(1):112–114. doi: 10.1096/fj.02-0067fje. [DOI] [PubMed] [Google Scholar]
  25. Schomburg L., Bauer K. Thyroid hormones rapidly and stringently regulate the messenger RNA levels of the thyrotropin-releasing hormone (TRH) receptor and the TRH-degrading ectoenzyme. Endocrinology. 1995 Aug;136(8):3480–3485. doi: 10.1210/endo.136.8.7628384. [DOI] [PubMed] [Google Scholar]
  26. Sheehan T. M., Gao M. Simplified fluorometric assay of total selenium in plasma and urine. Clin Chem. 1990 Dec;36(12):2124–2126. [PubMed] [Google Scholar]
  27. Spallholz J. E. Free radical generation by selenium compounds and their prooxidant toxicity. Biomed Environ Sci. 1997 Sep;10(2-3):260–270. [PubMed] [Google Scholar]
  28. Steinert P., Bächner D., Flohé L. Analysis of the mouse selenoprotein P gene. Biol Chem. 1998 Jun;379(6):683–691. doi: 10.1515/bchm.1998.379.6.683. [DOI] [PubMed] [Google Scholar]
  29. Takebe Gen, Yarimizu Junko, Saito Yoshiro, Hayashi Takaaki, Nakamura Hajime, Yodoi Junji, Nagasawa Shigeharu, Takahashi Kazuhiko. A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P. J Biol Chem. 2002 Aug 15;277(43):41254–41258. doi: 10.1074/jbc.M202773200. [DOI] [PubMed] [Google Scholar]
  30. Thanbichler Martin, Böck August. Selenoprotein biosynthesis: purification and assay of components involved in selenocysteine biosynthesis and insertion in Escherichia coli. Methods Enzymol. 2002;347:3–16. doi: 10.1016/s0076-6879(02)47003-6. [DOI] [PubMed] [Google Scholar]
  31. Thompson K. M., Haibach H., Sunde R. A. Growth and plasma triiodothyronine concentrations are modified by selenium deficiency and repletion in second-generation selenium-deficient rats. J Nutr. 1995 Apr;125(4):864–873. doi: 10.1093/jn/125.4.864. [DOI] [PubMed] [Google Scholar]
  32. Yoneda S., Suzuki K. T. Equimolar Hg-Se complex binds to selenoprotein P. Biochem Biophys Res Commun. 1997 Feb 3;231(1):7–11. doi: 10.1006/bbrc.1996.6036. [DOI] [PubMed] [Google Scholar]

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