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The human selenoproteome: recent insights into functions and regulation

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Abstract

Selenium (Se) is a nutritional trace mineral essential for various aspects of human health that exerts its effects mainly through its incorporation into selenoproteins as the amino acid, selenocysteine. Twenty-five selenoprotein genes have been identified in humans and several selenoproteins are broadly classified as antioxidant enzymes. As progress is made on characterizing the individual members of this protein family, however, it is becoming clear that their properties and functions are quite diverse. This review summarizes recent insights into properties of individual selenoproteins such as tissue distribution, subcellular localization, and regulation of expression. Also discussed are potential roles the different selenoproteins play in human health and disease.

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References

  1. Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241

    Article  PubMed  CAS  Google Scholar 

  2. Yang GQ, Ge KY, Chen JS, Chen XS (1988) Selenium-related endemic diseases and the daily selenium requirement of humans. World Rev Nutr Diet 55:98–152

    PubMed  CAS  Google Scholar 

  3. Zhou BF, Stamler J, Dennis B, Moag-Stahlberg A, Okuda N, Robertson C, Zhao L, Chan Q, Elliott P (2003) Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: the INTERMAP study. J Hum Hypertens 17:623–630

    Article  PubMed  CAS  Google Scholar 

  4. Hoffmann PR, Berry MJ (2008) The influence of selenium on immune responses. Mol Nutr Food Res 52:1273–1280

    Article  PubMed  CAS  Google Scholar 

  5. Gromadzinska J, Reszka E, Bruzelius K, Wasowicz W, Akesson B (2008) Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements. Eur J Nutr 47(Suppl. 2):29–50

    Article  PubMed  CAS  Google Scholar 

  6. Taylor PR, Albanes D (1998) Selenium, vitamin E, and prostate cancer—ready for prime time? J Natl Cancer Inst 90:1184–1185

    Article  PubMed  CAS  Google Scholar 

  7. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276:1957–1963

    Article  PubMed  CAS  Google Scholar 

  8. Duffield-Lillico AJ, Dalkin BL, Reid ME, Turnbull BW, Slate EH, Jacobs ET, Marshall JR, Clark LC (2003) Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int 91:608–612

    Article  PubMed  CAS  Google Scholar 

  9. Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden JD 3rd, Crawford ED, Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens FL Jr, Baker LH, Coltman CA Jr (2009) Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 301:39–51

    Article  PubMed  CAS  Google Scholar 

  10. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443

    Article  PubMed  CAS  Google Scholar 

  11. Kim HY, Gladyshev VN (2005) Different catalytic mechanisms in mammalian selenocysteine- and cysteine-containing methionine-R-sulfoxide reductases. PLoS Biol 3:e375

    Article  PubMed  CAS  Google Scholar 

  12. Lobanov AV, Hatfield DL, Gladyshev VN (2008) Reduced reliance on the trace element selenium during evolution of mammals. Genome Biol 9:R62

    Article  PubMed  CAS  Google Scholar 

  13. Bosl MR, Takaku K, Oshima M, Nishimura S, Taketo MM (1997) Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene (Trsp). Proc Natl Acad Sci USA 94:5531–5534

    Article  PubMed  CAS  Google Scholar 

  14. Suzuki T, Kelly VP, Motohashi H, Nakajima O, Takahashi S, Nishimura S, Yamamoto M (2008) Deletion of the selenocysteine tRNA gene in macrophages and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2. J Biol Chem 283:2021–2030

    Article  PubMed  CAS  Google Scholar 

  15. Lu J, Holmgren A (2009) Selenoproteins. J Biol Chem 284:723–727

    Article  PubMed  CAS  Google Scholar 

  16. Hoffmann PR, Berry MJ (2005) Selenoprotein synthesis: a unique translational mechanism used by a diverse family of proteins. Thyroid 15:769–775

    Article  PubMed  CAS  Google Scholar 

  17. Papp LV, Lu J, Holmgren A, Khanna KK (2007) From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal 9:775–806

    Article  PubMed  CAS  Google Scholar 

  18. Squires JE, Berry MJ (2008) Eukaryotic selenoprotein synthesis: mechanistic insight incorporating new factors and new functions for old factors. IUBMB Life 60:232–235

    Article  PubMed  CAS  Google Scholar 

  19. Shchedrina VA, Novoselov SV, Malinouski MY, Gladyshev VN (2007) Identification and characterization of a selenoprotein family containing a diselenide bond in a redox motif. Proc Natl Acad Sci USA 104:13919–13924

    Article  PubMed  CAS  Google Scholar 

  20. Hill KE, Lloyd RS, Burk RF (1993) Conserved nucleotide sequences in the open reading frame and 3’ untranslated region of selenoprotein P mRNA. Proc Natl Acad Sci USA 90:537–541

    Article  PubMed  CAS  Google Scholar 

  21. Berry MJ, Banu L, Harney JW, Larsen PR (1993) Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. EMBO J 12:3315–3322

    PubMed  CAS  Google Scholar 

  22. Lee BJ, Worland PJ, Davis JN, Stadtman TC, Hatfield DL (1989) Identification of a selenocysteyl-tRNA(Ser) in mammalian cells that recognizes the nonsense codon, UGA. J Biol Chem 264:9724–9727

    PubMed  CAS  Google Scholar 

  23. Xu XM, Carlson BA, Mix H, Zhang Y, Saira K, Glass RS, Berry MJ, Gladyshev VN, Hatfield DL (2007) Biosynthesis of selenocysteine on its tRNA in eukaryotes. PLoS Biol 5:e4

    Article  PubMed  CAS  Google Scholar 

  24. Carlson BA, Xu XM, Kryukov GV, Rao M, Berry MJ, Gladyshev VN, Hatfield DL (2004) Identification and characterization of phosphoseryl-tRNA[Ser]Sec kinase. Proc Natl Acad Sci USA 101:12848–12853

    Article  PubMed  CAS  Google Scholar 

  25. Small-Howard A, Morozova N, Stoytcheva Z, Forry EP, Mansell JB, Harney JW, Carlson BA, Xu XM, Hatfield DL, Berry MJ (2006) Supramolecular complexes mediate selenocysteine incorporation in vivo. Mol Cell Biol 26:2337–2346

    Article  PubMed  CAS  Google Scholar 

  26. Xu XM, Mix H, Carlson BA, Grabowski PJ, Gladyshev VN, Berry MJ, Hatfield DL (2005) Evidence for direct roles of two additional factors, SECp43 and soluble liver antigen, in the selenoprotein synthesis machinery. J Biol Chem 280:41568–41575

    Article  PubMed  CAS  Google Scholar 

  27. Copeland PR, Fletcher JE, Carlson BA, Hatfield DL, Driscoll DM (2000) A novel RNA binding protein, SBP2, is required for the translation of mammalian selenoprotein mRNAs. EMBO J 19:306–314

    Article  PubMed  CAS  Google Scholar 

  28. de Jesus LA, Hoffmann PR, Michaud T, Forry EP, Small-Howard A, Stillwell RJ, Morozova N, Harney JW, Berry MJ (2006) Nuclear assembly of UGA decoding complexes on selenoprotein mRNAs: a mechanism for eluding nonsense-mediated decay? Mol Cell Biol 26:1795–1805

    Article  PubMed  CAS  Google Scholar 

  29. Tujebajeva RM, Copeland PR, Xu XM, Carlson BA, Harney JW, Driscoll DM, Hatfield DL, Berry MJ (2000) Decoding apparatus for eukaryotic selenocysteine insertion. EMBO Rep 1:158–163

    Article  PubMed  CAS  Google Scholar 

  30. Fagegaltier D, Hubert N, Yamada K, Mizutani T, Carbon P, Krol A (2000) Characterization of mSelB, a novel mammalian elongation factor for selenoprotein translation. EMBO J 19:4796–4805

    Article  PubMed  CAS  Google Scholar 

  31. Chavatte L, Brown BA, Driscoll DM (2005) Ribosomal protein L30 is a component of the UGA-selenocysteine recoding machinery in eukaryotes. Nat Struct Mol Biol 12:408–416

    Article  PubMed  CAS  Google Scholar 

  32. Wu R, Shen Q, Newburger PE (2000) Recognition and binding of the human selenocysteine insertion sequence by nucleolin. J Cell Biochem 77:507–516

    Article  PubMed  CAS  Google Scholar 

  33. Carlson BA, Schweizer U, Perella C, Shrimali RK, Feigenbaum L, Shen L, Speransky S, Floss T, Jeong SJ, Watts J, Hoffmann V, Combs GF, Gladyshev VN, Hatfield DL (2009) The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice. Biochem J 418:61–71

    Article  PubMed  CAS  Google Scholar 

  34. Howard MT, Moyle MW, Aggarwal G, Carlson BA, Anderson CB (2007) A recoding element that stimulates decoding of UGA codons by Sec tRNA[Ser]Sec. RNA 13:912–920

    Article  PubMed  CAS  Google Scholar 

  35. Maiti B, Arbogast S, Allamand V, Moyle MW, Anderson CB, Richard P, Guicheney P, Ferreiro A, Flanigan KM, Howard MT (2009) A mutation in the SEPN1 selenocysteine redefinition element (SRE) reduces selenocysteine incorporation and leads to SEPN1-related myopathy. Hum Mutat 3:411–416

    Article  CAS  Google Scholar 

  36. Moriarty PM, Reddy CC, Maquat LE (1998) Selenium deficiency reduces the abundance of mRNA for Se-dependent glutathione peroxidase 1 by a UGA-dependent mechanism likely to be nonsense codon-mediated decay of cytoplasmic mRNA. Mol Cell Biol 18:2932–2939

    PubMed  CAS  Google Scholar 

  37. Weiss Sachdev S, Sunde RA (2001) Selenium regulation of transcript abundance and translational efficiency of glutathione peroxidase-1 and -4 in rat liver. Biochem J 357:851–858

    Article  PubMed  CAS  Google Scholar 

  38. Sunde RA, Raines AM, Barnes KM, Evenson JK (2008) Selenium status highly-regulates selenoprotein mRNA levels for only a subset of the selenoproteins in the selenoproteome. Biosci Rep doi:10.1042/BSR20080146

  39. Muller C, Wingler K, Brigelius-Flohe R (2003) 3′UTRs of glutathione peroxidases differentially affect selenium-dependent mRNA stability and selenocysteine incorporation efficiency. Biol Chem 384:11–18

    Article  PubMed  CAS  Google Scholar 

  40. Squires JE, Stoytchev I, Forry EP, Berry MJ (2007) SBP2 binding affinity is a major determinant in differential selenoprotein mRNA translation and sensitivity to nonsense-mediated decay. Mol Cell Biol 27:7848–7855

    Article  PubMed  CAS  Google Scholar 

  41. Carlson BA, Xu XM, Gladyshev VN, Hatfield DL (2005) Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA. J Biol Chem 280:5542–5548

    Article  PubMed  CAS  Google Scholar 

  42. Flohe L, Gunzler WA, Schock HH (1973) Glutathione peroxidase: a selenoenzyme. FEBS Lett 32:132–134

    Article  PubMed  CAS  Google Scholar 

  43. Forstrom JW, Zakowski JJ, Tappel AL (1978) Identification of the catalytic site of rat liver glutathione peroxidase as selenocysteine. Biochemistry 17:2639–2644

    Article  PubMed  CAS  Google Scholar 

  44. Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrison PR (1986) The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the ‘termination’ codon, TGA. EMBO J 5:1221–1227

    PubMed  CAS  Google Scholar 

  45. Margis R, Dunand C, Teixeira FK, Margis-Pinheiro M (2008) Glutathione peroxidase family: an evolutionary overview. FEBS J 275:3959–3970

    Article  PubMed  CAS  Google Scholar 

  46. Cheng WH, Ho YS, Ross DA, Valentine BA, Combs GF, Lei XG (1997) Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues. J Nutr 127:1445–1450

    PubMed  CAS  Google Scholar 

  47. Lei XG, Cheng WH, McClung JP (2007) Metabolic regulation and function of glutathione peroxidase-1. Annu Rev Nutr 27:41–61

    Article  PubMed  CAS  Google Scholar 

  48. Cheng W, Fu YX, Porres JM, Ross DA, Lei XG (1999) Selenium-dependent cellular glutathione peroxidase protects mice against a pro-oxidant-induced oxidation of NADPH, NADH, lipids, and protein. FASEB J 13:1467–1475

    PubMed  CAS  Google Scholar 

  49. Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6:318–327

    Article  PubMed  CAS  Google Scholar 

  50. Rahman I, MacNee W (2000) Oxidative stress and regulation of glutathione in lung inflammation. Eur Respir J 16:534–554

    Article  PubMed  CAS  Google Scholar 

  51. Rahman I, Mulier B, Gilmour PS, Watchorn T, Donaldson K, Jeffery PK, MacNee W (2001) Oxidant-mediated lung epithelial cell tolerance: the role of intracellular glutathione and nuclear factor-kappaB. Biochem Pharmacol 62:787–794

    Article  PubMed  CAS  Google Scholar 

  52. Hoffmann PR, Jourdan-Le Saux C, Hoffmann FW, Chang PS, Bollt O, He Q, Tam EK, Berry MJ (2007) A role for dietary selenium and selenoproteins in allergic airway inflammation. J Immunol 179:3258–3267

    PubMed  CAS  Google Scholar 

  53. Fitzpatrick AM, Teague WG, Holguin F, Yeh M, Brown LA (2009) Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress. J Allergy Clin Immunol 123:146–152 e8

    Article  PubMed  CAS  Google Scholar 

  54. Hoffmann PR (2008) Selenium and asthma: a complex relationship. Allergy 63:854–856

    Article  PubMed  CAS  Google Scholar 

  55. Esworthy RS, Baker MA, Chu FF (1995) Expression of selenium-dependent glutathione peroxidase in human breast tumor cell lines. Cancer Res 55:957–962

    PubMed  CAS  Google Scholar 

  56. Gladyshev VN, Factor VM, Housseau F, Hatfield DL (1998) Contrasting patterns of regulation of the antioxidant selenoproteins, thioredoxin reductase, and glutathione peroxidase, in cancer cells. Biochem Biophys Res Commun 251:488–493

    Article  PubMed  CAS  Google Scholar 

  57. Jee CD, Kim MA, Jung EJ, Kim J, Kim WH (2009) Identification of genes epigenetically silenced by CpG methylation in human gastric carcinoma. Eur J Cancer doi:10.1016/j.ejca.2008.12.027

  58. Gresner P, Gromadzinska J, Jablonska E, Kaczmarski J, Wasowicz W (2008) Expression of selenoprotein-coding genes SEPP1, SEP15 and hGPX1 in non-small cell lung cancer. Lung Cancer. doi:10.1016/j.lungcan.2008.10.023

  59. Arsova-Sarafinovska Z, Matevska N, Eken A, Petrovski D, Banev S, Dzikova S, Georgiev V, Sikole A, Erdem O, Sayal A, Aydin A, Dimovski AJ (2008) Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. Int Urol Nephrol 41:63–70

    Article  PubMed  CAS  Google Scholar 

  60. Baliga MS, Wang H, Zhuo P, Schwartz JL, Diamond AM (2007) Selenium and GPx-1 overexpression protect mammalian cells against UV-induced DNA damage. Biol Trace Elem Res 115:227–242

    Article  PubMed  CAS  Google Scholar 

  61. Trepanier G, Furling D, Puymirat J, Mirault ME (1996) Immunocytochemical localization of seleno-glutathione peroxidase in the adult mouse brain. Neuroscience 75:231–243

    Article  PubMed  CAS  Google Scholar 

  62. Lindenau J, Noack H, Asayama K, Wolf G (1998) Enhanced cellular glutathione peroxidase immunoreactivity in activated astrocytes and in microglia during excitotoxin induced neurodegeneration. Glia 24:252–256

    Article  PubMed  CAS  Google Scholar 

  63. Power JH, Blumbergs PC (2009) Cellular glutathione peroxidase in human brain: cellular distribution, and its potential role in the degradation of Lewy bodies in Parkinson’s disease and dementia with Lewy bodies. Acta Neuropathol 117:63–73

    Article  PubMed  CAS  Google Scholar 

  64. Ho YS, Magnenat JL, Bronson RT, Cao J, Gargano M, Sugawara M, Funk CD (1997) Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 272:16644–16651

    Article  PubMed  CAS  Google Scholar 

  65. Cheng WH, Ho YS, Valentine BA, Ross DA, Combs GF Jr, Lei XG (1998) Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice. J Nutr 128:1070–1076

    PubMed  CAS  Google Scholar 

  66. de Haan JB, Bladier C, Griffiths P, Kelner M, O’Shea RD, Cheung NS, Bronson RT, Silvestro MJ, Wild S, Zheng SS, Beart PM, Hertzog PJ, Kola I (1998) Mice with a homozygous null mutation for the most abundant glutathione peroxidase, GPx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J Biol Chem 273:22528–22536

    Article  PubMed  Google Scholar 

  67. Beck MA, Esworthy RS, Ho YS, Chu FF (1998) Glutathione peroxidase protects mice from viral-induced myocarditis. FASEB J 12:1143–1149

    PubMed  CAS  Google Scholar 

  68. McClung JP, Roneker CA, Mu W, Lisk DJ, Langlais P, Liu F, Lei XG (2004) Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. Proc Natl Acad Sci USA 101:8852–8857

    Article  PubMed  CAS  Google Scholar 

  69. Wang XD, Vatamaniuk MZ, Wang SK, Roneker CA, Simmons RA, Lei XG (2008) Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice. Diabetologia 51:1515–1524

    Article  PubMed  CAS  Google Scholar 

  70. Chen X, Scholl TO, Leskiw MJ, Donaldson MR, Stein TP (2003) Association of glutathione peroxidase activity with insulin resistance and dietary fat intake during normal pregnancy. J Clin Endocrinol Metab 88:5963–5968

    Article  PubMed  CAS  Google Scholar 

  71. Wingler K, Brigelius-Flohe R (1999) Gastrointestinal glutathione peroxidase. Biofactors 10:245–249

    Article  PubMed  CAS  Google Scholar 

  72. Florian S, Wingler K, Schmehl K, Jacobasch G, Kreuzer OJ, Meyerhof W, Brigelius-Flohe R (2001) Cellular and subcellular localization of gastrointestinal glutathione peroxidase in normal and malignant human intestinal tissue. Free Radic Res 35:655–663

    Article  PubMed  CAS  Google Scholar 

  73. Chu FF, Esworthy RS, Ho YS, Bermeister M, Swiderek K, Elliott RW (1997) Expression and chromosomal mapping of mouse GPx2 gene encoding the gastrointestinal form of glutathione peroxidase, GPX-GI. Biomed Environ Sci 10:156–162

    PubMed  CAS  Google Scholar 

  74. Esworthy RS, Swiderek KM, Ho YS, Chu FF (1998) Selenium-dependent glutathione peroxidase-GI is a major glutathione peroxidase activity in the mucosal epithelium of rodent intestine. Biochim Biophys Acta 1381:213–226

    PubMed  CAS  Google Scholar 

  75. Chu FF, Doroshow JH, Esworthy RS (1993) Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. J Biol Chem 268:2571–2576

    PubMed  CAS  Google Scholar 

  76. Wingler K, Bocher M, Flohe L, Kollmus H, Brigelius-Flohe R (1999) mRNA stability and selenocysteine insertion sequence efficiency rank gastrointestinal glutathione peroxidase high in the hierarchy of selenoproteins. Eur J Biochem 259:149–157

    Article  PubMed  CAS  Google Scholar 

  77. Murawaki Y, Tsuchiya H, Kanbe T, Harada K, Yashima K, Nozaka K, Tanida O, Kohno M, Mukoyama T, Nishimuki E, Kojo H, Matsura T, Takahashi K, Osaki M, Ito H, Yodoi J, Murawaki Y, Shiota G (2008) Aberrant expression of selenoproteins in the progression of colorectal cancer. Cancer Lett 259:218–230

    Article  PubMed  CAS  Google Scholar 

  78. Mork H, Scheurlen M, Al-Taie O, Zierer A, Kraus M, Schottker K, Jakob F, Kohrle J (2003) Glutathione peroxidase isoforms as part of the local antioxidative defense system in normal and Barrett’s esophagus. Int J Cancer 105:300–304

    Article  PubMed  CAS  Google Scholar 

  79. Serewko MM, Popa C, Dahler AL, Smith L, Strutton GM, Coman W, Dicker AJ, Saunders NA (2002) Alterations in gene expression and activity during squamous cell carcinoma development. Cancer Res 62:3759–3765

    PubMed  CAS  Google Scholar 

  80. Chu FF, Esworthy RS, Chu PG, Longmate JA, Huycke MM, Wilczynski S, Doroshow JH (2004) Bacteria-induced intestinal cancer in mice with disrupted GPx1 and GPx2 genes. Cancer Res 64:962–968

    Article  PubMed  CAS  Google Scholar 

  81. Esworthy RS, Yang L, Frankel PH, Chu FF (2005) Epithelium-specific glutathione peroxidase, GPx2, is involved in the prevention of intestinal inflammation in selenium-deficient mice. J Nutr 135:740–745

    PubMed  CAS  Google Scholar 

  82. Banning A, Kipp A, Schmitmeier S, Lowinger M, Florian S, Krehl S, Thalmann S, Thierbach R, Steinberg P, Brigelius-Flohe R (2008) Glutathione peroxidase 2 inhibits cyclooxygenase-2-mediated migration and invasion of HT-29 adenocarcinoma cells but supports their growth as tumors in nude mice. Cancer Res 68:9746–9753

    Article  PubMed  CAS  Google Scholar 

  83. Koyama H, Omura K, Ejima A, Kasanuma Y, Watanabe C, Satoh H (1999) Separation of selenium-containing proteins in human and mouse plasma using tandem high-performance liquid chromatography columns coupled with inductively coupled plasma-mass spectrometry. Anal Biochem 267:84–91

    Article  PubMed  CAS  Google Scholar 

  84. Burk RF, Hill KE (2005) Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annu Rev Nutr 25:215–235

    Article  PubMed  CAS  Google Scholar 

  85. Yoshimura S, Watanabe K, Suemizu H, Onozawa T, Mizoguchi J, Tsuda K, Hatta H, Moriuchi T (1991) Tissue specific expression of the plasma glutathione peroxidase gene in rat kidney. J Biochem 109:918–923

    PubMed  CAS  Google Scholar 

  86. Hoffmann PR, Hoge SC, Li PA, Hoffmann FW, Hashimoto AC, Berry MJ (2007) The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply. Nucleic Acids Res 35:3963–3973

    Article  PubMed  CAS  Google Scholar 

  87. Schmutzler C, Mentrup B, Schomburg L, Hoang-Vu C, Herzog V, Kohrle J (2007) Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3. Biol Chem 388:1053–1059

    Article  PubMed  CAS  Google Scholar 

  88. Ottaviano FG, Tang SS, Handy DE, Loscalzo J (2009) Regulation of the extracellular antioxidant selenoprotein plasma glutathione peroxidase (GPx-3) in mammalian cells. Mol Cell Biochem doi: 10.1007/s11010-009-0049-x

  89. Bjornstedt M, Xue J, Huang W, Akesson B, Holmgren A (1994) The thioredoxin and glutaredoxin systems are efficient electron donors to human plasma glutathione peroxidase. J Biol Chem 269:29382–29384

    PubMed  CAS  Google Scholar 

  90. Freedman JE, Frei B, Welch GN, Loscalzo J (1995) Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols. J Clin Invest 96:394–400

    Article  PubMed  CAS  Google Scholar 

  91. Freedman JE, Loscalzo J, Benoit SE, Valeri CR, Barnard MR, Michelson AD (1996) Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis. J Clin Invest 97:979–987

    Article  PubMed  CAS  Google Scholar 

  92. Kenet G, Freedman J, Shenkman B, Regina E, Brok-Simoni F, Holzman F, Vavva F, Brand N, Michelson A, Trolliet M, Loscalzo J, Inbal A (1999) Plasma glutathione peroxidase deficiency and platelet insensitivity to nitric oxide in children with familial stroke. Arterioscler Thromb Vasc Biol 19:2017–2023

    PubMed  CAS  Google Scholar 

  93. Bierl C, Voetsch B, Jin RC, Handy DE, Loscalzo J (2004) Determinants of human plasma glutathione peroxidase (GPx-3) expression. J Biol Chem 279:26839–26845

    Article  PubMed  CAS  Google Scholar 

  94. Voetsch B, Jin RC, Bierl C, Benke KS, Kenet G, Simioni P, Ottaviano F, Damasceno BP, Annichino-Bizacchi JM, Handy DE, Loscalzo J (2007) Promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene: a novel risk factor for arterial ischemic stroke among young adults and children. Stroke 38:41–49

    Article  PubMed  CAS  Google Scholar 

  95. Voetsch B, Jin RC, Bierl C, Deus-Silva L, Camargo EC, Annichino-Bizacchi JM, Handy DE, Loscalzo J (2008) Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis. Stroke 39:303–307

    Article  PubMed  CAS  Google Scholar 

  96. Grond-Ginsbach C, Arnold ML, Lichy C, Grau A, Reuner K (2009) No association of the plasma glutathione peroxidase (GPx-3) gene with cerebral venous thrombosis in the German population. Stroke 40:e24 author reply e25

    Article  PubMed  CAS  Google Scholar 

  97. Chung SS, Kim M, Youn BS, Lee NS, Park JW, Lee IK, Lee YS, Kim JB, Cho YM, Lee HK, Park KS (2009) Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells. Mol Cell Biol 29:20–30

    Article  PubMed  CAS  Google Scholar 

  98. Lee YS, Kim AY, Choi JW, Kim M, Yasue S, Son HJ, Masuzaki H, Park KS, Kim JB (2008) Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress. Mol Endocrinol 22:2176–2189

    Article  PubMed  CAS  Google Scholar 

  99. Lundholm L, Putnik M, Otsuki M, Andersson S, Ohlsson C, Gustafsson JA, Dahlman-Wright K (2008) Effects of estrogen on gene expression profiles in mouse hypothalamus and white adipose tissue: target genes include glutathione peroxidase 3 and cell death-inducing DNA fragmentation factor, alpha-subunit-like effector A. J Endocrinol 196:547–557

    Article  PubMed  CAS  Google Scholar 

  100. Conrad M, Schneider M, Seiler A, Bornkamm GW (2007) Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals. Biol Chem 388:1019–1025

    Article  PubMed  CAS  Google Scholar 

  101. Yant LJ, Ran Q, Rao L, Van Remmen H, Shibatani T, Belter JG, Motta L, Richardson A, Prolla TA (2003) The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic Biol Med 34:496–502

    Article  PubMed  CAS  Google Scholar 

  102. Conrad M, Moreno SG, Sinowatz F, Ursini F, Kolle S, Roveri A, Brielmeier M, Wurst W, Maiorino M, Bornkamm GW (2005) The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability. Mol Cell Biol 25:7637–7644

    Article  PubMed  CAS  Google Scholar 

  103. Chen CJ, Huang HS, Chang WC (2003) Depletion of phospholipid hydroperoxide glutathione peroxidase up-regulates arachidonate metabolism by 12S-lipoxygenase and cyclooxygenase 1 in human epidermoid carcinoma A431 cells. FASEB J 17:1694–1696

    Article  PubMed  CAS  Google Scholar 

  104. Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E, Radmark O, Wurst W, Bornkamm GW, Schweizer U, Conrad M (2008) Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8:237–248

    Article  PubMed  CAS  Google Scholar 

  105. Imai H, Hirao F, Sakamoto T, Sekine K, Mizukura Y, Saito M, Kitamoto T, Hayasaka M, Hanaoka K, Nakagawa Y (2003) Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene. Biochem Biophys Res Commun 305:278–286

    Article  PubMed  CAS  Google Scholar 

  106. Ufer C, Wang CC, Fahling M, Schiebel H, Thiele BJ, Billett EE, Kuhn H, Borchert A (2008) Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development. Genes Dev 22:1838–1850

    Article  PubMed  CAS  Google Scholar 

  107. Blackinton J, Kumaran R, van der Brug MP, Ahmad R, Olson L, Galter D, Lees A, Bandopadhyay R, Cookson MR (2009) Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease. Neurosci Lett doi:10.1016/j.neulet.2008.12.053

  108. Chen L, Na R, Gu M, Richardson A, Ran Q (2008) Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer’s disease. J Neurochem 107:197–207

    Article  PubMed  CAS  Google Scholar 

  109. Guo Z, Ran Q, Roberts LJ 2nd, Zhou L, Richardson A, Sharan C, Wu D, Yang H (2008) Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Free Radic Biol Med 44:343–352

    Article  PubMed  CAS  Google Scholar 

  110. Dabkowski ER, Williamson CL, Hollander JM (2008) Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac dysfunction. Free Radic Biol Med 45:855–865

    Article  PubMed  CAS  Google Scholar 

  111. Ursini F, Heim S, Kiess M, Maiorino M, Roveri A, Wissing J, Flohe L (1999) Dual function of the selenoprotein PHGPx during sperm maturation. Science 285:1393–1396

    Article  PubMed  CAS  Google Scholar 

  112. Flohe L (2007) Selenium in mammalian spermiogenesis. Biol Chem 388:987–995

    Article  PubMed  CAS  Google Scholar 

  113. Foresta C, Flohe L, Garolla A, Roveri A, Ursini F, Maiorino M (2002) Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol Reprod 67:967–971

    Article  PubMed  CAS  Google Scholar 

  114. Holmgren A (1989) Thioredoxin and glutaredoxin systems. J Biol Chem 264:13963–13966

    PubMed  CAS  Google Scholar 

  115. Arner ES, Holmgren A (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 267:6102–6109

    Article  PubMed  CAS  Google Scholar 

  116. Gilbert HF (1990) Molecular and cellular aspects of thiol-disulfide exchange. Adv Enzymol Relat Areas Mol Biol 63:69–172

    Article  PubMed  CAS  Google Scholar 

  117. Zhong L, Arner ES, Holmgren A (2000) Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. Proc Natl Acad Sci USA 97:5854–5859

    Article  PubMed  CAS  Google Scholar 

  118. Gladyshev VN, Jeang KT, Stadtman TC (1996) Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc Natl Acad Sci USA 93:6146–6151

    Article  PubMed  CAS  Google Scholar 

  119. Lacey BM, Eckenroth BE, Flemer S, Hondal RJ (2008) Selenium in thioredoxin reductase: a mechanistic perspective. Biochemistry 47:12810–12821

    Article  PubMed  CAS  Google Scholar 

  120. Miranda-Vizuete A, Damdimopoulos AE, Spyrou G (1999) cDNA cloning, expression and chromosomal localization of the mouse mitochondrial thioredoxin reductase gene(1). Biochim Biophys Acta 1447:113–118

    PubMed  CAS  Google Scholar 

  121. Mustacich D, Powis G (2000) Thioredoxin reductase. Biochem J 346(Pt 1):1–8

    Article  PubMed  CAS  Google Scholar 

  122. Watson WH, Heilman JM, Hughes LL, Spielberger JC (2008) Thioredoxin reductase-1 knock down does not result in thioredoxin-1 oxidation. Biochem Biophys Res Commun 368:832–836

    Article  PubMed  CAS  Google Scholar 

  123. Andersson M, Holmgren A, Spyrou G (1996) NK-lysin, a disulfide-containing effector peptide of T-lymphocytes, is reduced and inactivated by human thioredoxin reductase. Implication for a protective mechanism against NK-lysin cytotoxicity. J Biol Chem 271:10116–10120

    Article  PubMed  CAS  Google Scholar 

  124. Holmgren A, Lyckeborg C (1980) Enzymatic reduction of alloxan by thioredoxin and NADPH-thioredoxin reductase. Proc Natl Acad Sci USA 77:5149–5152

    Article  PubMed  CAS  Google Scholar 

  125. Arner ES, Nordberg J, Holmgren A (1996) Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase. Biochem Biophys Res Commun 225:268–274

    Article  PubMed  CAS  Google Scholar 

  126. Kumar S, Bjornstedt M, Holmgren A (1992) Selenite is a substrate for calf thymus thioredoxin reductase and thioredoxin and elicits a large non-stoichiometric oxidation of NADPH in the presence of oxygen. Eur J Biochem 207:435–439

    Article  PubMed  CAS  Google Scholar 

  127. Osborne SA, Tonissen KF (2001) Genomic organisation and alternative splicing of mouse and human thioredoxin reductase 1 genes. BMC Genomics 2:10

    Article  PubMed  CAS  Google Scholar 

  128. Sun QA, Zappacosta F, Factor VM, Wirth PJ, Hatfield DL, Gladyshev VN (2001) Heterogeneity within animal thioredoxin reductases. Evidence for alternative first exon splicing. J Biol Chem 276:3106–3114

    Article  PubMed  CAS  Google Scholar 

  129. Rundlof AK, Janard M, Miranda-Vizuete A, Arner ES (2004) Evidence for intriguingly complex transcription of human thioredoxin reductase 1. Free Radic Biol Med 36:641–656

    Article  PubMed  CAS  Google Scholar 

  130. Turanov AA, Su D, Gladyshev VN (2006) Characterization of alternative cytosolic forms and cellular targets of mouse mitochondrial thioredoxin reductase. J Biol Chem 281:22953–22963

    Article  PubMed  CAS  Google Scholar 

  131. Dammeyer P, Damdimopoulos AE, Nordman T, Jimenez A, Miranda-Vizuete A, Arner ES (2008) Induction of cell membrane protrusions by the N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin reductase 1. J Biol Chem 283:2814–2821

    Article  PubMed  CAS  Google Scholar 

  132. Rundlof AK, Carlsten M, Arner ES (2001) The core promoter of human thioredoxin reductase 1: cloning, transcriptional activity, and Oct-1, Sp1, and Sp3 binding reveal a housekeeping-type promoter for the AU-rich element-regulated gene. J Biol Chem 276:30542–30551

    Article  PubMed  CAS  Google Scholar 

  133. Crosley LK, Meplan C, Nicol F, Rundlof AK, Arner ES, Hesketh JE, Arthur JR (2007) Differential regulation of expression of cytosolic and mitochondrial thioredoxin reductase in rat liver and kidney. Arch Biochem Biophys 459:178–188

    Article  PubMed  CAS  Google Scholar 

  134. Carlson BA, Moustafa ME, Sengupta A, Schweizer U, Shrimali R, Rao M, Zhong N, Wang S, Feigenbaum L, Lee BJ, Gladyshev VN, Hatfield DL (2007) Selective restoration of the selenoprotein population in a mouse hepatocyte selenoproteinless background with different mutant selenocysteine tRNAs lacking Um34. J Biol Chem 282:32591–32602

    Article  PubMed  CAS  Google Scholar 

  135. Jakupoglu C, Przemeck GK, Schneider M, Moreno SG, Mayr N, Hatzopoulos AK, de Angelis MH, Wurst W, Bornkamm GW, Brielmeier M, Conrad M (2005) Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development. Mol Cell Biol 25:1980–1988

    Article  PubMed  CAS  Google Scholar 

  136. Conrad M, Jakupoglu C, Moreno SG, Lippl S, Banjac A, Schneider M, Beck H, Hatzopoulos AK, Just U, Sinowatz F, Schmahl W, Chien KR, Wurst W, Bornkamm GW, Brielmeier M (2004) Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol Cell Biol 24:9414–9423

    Article  PubMed  CAS  Google Scholar 

  137. Geisberger R, Kiermayer C, Homig C, Conrad M, Schmidt J, Zimber-Strobl U, Brielmeier M (2007) B- and T-cell-specific inactivation of thioredoxin reductase 2 does not impair lymphocyte development and maintenance. Biol Chem 388:1083–1090

    Article  PubMed  CAS  Google Scholar 

  138. Gandin V, Nystrom C, Rundlof AK, Jonsson-Videsater K, Schonlau F, Horkko J, Bjornstedt M, Fernandes AP (2009) Effects of the antioxidant Pycnogenol on cellular redox systems in U1285 human lung carcinoma cells. FEBS J 276:532–540

    Article  PubMed  CAS  Google Scholar 

  139. Sakurai A, Nishimoto M, Himeno S, Imura N, Tsujimoto M, Kunimoto M, Hara S (2005) Transcriptional regulation of thioredoxin reductase 1 expression by cadmium in vascular endothelial cells: role of NF-E2-related factor-2. J Cell Physiol 203:529–537

    Article  PubMed  CAS  Google Scholar 

  140. Rundlof AK, Arner ES (2004) Regulation of the mammalian selenoprotein thioredoxin reductase 1 in relation to cellular phenotype, growth, and signaling events. Antioxid Redox Signal 6:41–52

    Article  PubMed  CAS  Google Scholar 

  141. Kuster GM, Siwik DA, Pimentel DR, Colucci WS (2006) Role of reversible, thioredoxin-sensitive oxidative protein modifications in cardiac myocytes. Antioxid Redox Signal 8:2153–2159

    Article  PubMed  CAS  Google Scholar 

  142. Gladyshev VN, Stadtman TC, Hatfield DL, Jeang KT (1999) Levels of major selenoproteins in T cells decrease during HIV infection and low molecular mass selenium compounds increase. Proc Natl Acad Sci USA 96:835–839

    Article  PubMed  CAS  Google Scholar 

  143. Kalantari P, Narayan V, Natarajan SK, Muralidhar K, Gandhi UH, Vunta H, Henderson AJ, Prabhu KS (2008) Thioredoxin reductase-1 negatively regulates HIV-1 transactivating protein Tat-dependent transcription in human macrophages. J Biol Chem 283:33183–33190

    Article  PubMed  CAS  Google Scholar 

  144. Powis G, Kirkpatrick DL (2007) Thioredoxin signaling as a target for cancer therapy. Curr Opin Pharmacol 7:392–397

    Article  PubMed  CAS  Google Scholar 

  145. Lincoln DT, Ali Emadi EM, Tonissen KF, Clarke FM (2003) The thioredoxin–thioredoxin reductase system: over-expression in human cancer. Anticancer Res 23:2425–2433

    PubMed  CAS  Google Scholar 

  146. Yoo MH, Xu XM, Carlson BA, Gladyshev VN, Hatfield DL (2006) Thioredoxin reductase 1 deficiency reverses tumor phenotype and tumorigenicity of lung carcinoma cells. J Biol Chem 281:13005–13008

    Article  PubMed  CAS  Google Scholar 

  147. Yoo MH, Xu XM, Carlson BA, Patterson AD, Gladyshev VN, Hatfield DL (2007) Targeting thioredoxin reductase 1 reduction in cancer cells inhibits self-sufficient growth and DNA replication. PLoS ONE 2:e1112

    Article  PubMed  CAS  Google Scholar 

  148. Zahedi Avval F, Holmgren A (2009) Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for mammalian S-phase ribonucleotide reductase. J Biol Chem doi:10.1074/jbc.M809338200

  149. Sun Y, Rigas B (2008) The thioredoxin system mediates redox-induced cell death in human colon cancer cells: implications for the mechanism of action of anticancer agents. Cancer Res 68:8269–8277

    Article  PubMed  CAS  Google Scholar 

  150. Cheng Q, Sandalova T, Lindqvist Y, Arner ES (2009) Crystal structure and catalysis of the selenoprotein thioredoxin reductase 1. J Biol Chem 284:3998–4008

    Article  PubMed  CAS  Google Scholar 

  151. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23:38–89

    Article  PubMed  CAS  Google Scholar 

  152. Gereben B, Goncalves C, Harney JW, Larsen PR, Bianco AC (2000) Selective proteolysis of human type 2 deiodinase: a novel ubiquitin-proteasomal mediated mechanism for regulation of hormone activation. Mol Endocrinol 14:1697–1708

    Article  PubMed  CAS  Google Scholar 

  153. Steinsapir J, Harney J, Larsen PR (1998) Type 2 iodothyronine deiodinase in rat pituitary tumor cells is inactivated in proteasomes. J Clin Invest 102:1895–1899

    Article  PubMed  CAS  Google Scholar 

  154. Steinsapir J, Bianco AC, Buettner C, Harney J, Larsen PR (2000) Substrate-induced down-regulation of human type 2 deiodinase (hD2) is mediated through proteasomal degradation and requires interaction with the enzyme’s active center. Endocrinology 141:1127–1135

    Article  PubMed  CAS  Google Scholar 

  155. Hernandez A, St Germain DL (2003) Thyroid hormone deiodinases: physiology and clinical disorders. Curr Opin Pediatr 15:416–420

    PubMed  Google Scholar 

  156. Schneider MJ, Fiering SN, Pallud SE, Parlow AF, St Germain DL, Galton VA (2001) Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol Endocrinol 15:2137–2148

    Article  PubMed  CAS  Google Scholar 

  157. Schneider MJ, Fiering SN, Thai B, Wu SY, St Germain E, Parlow AF, St Germain DL, Galton VA (2006) Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 147:580–589

    Article  PubMed  CAS  Google Scholar 

  158. de Jesus LA, Carvalho SD, Ribeiro MO, Schneider M, Kim SW, Harney JW, Larsen PR, Bianco AC (2001) The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest 108:1379–1385

    PubMed  Google Scholar 

  159. Ng L, Goodyear RJ, Woods CA, Schneider MJ, Diamond E, Richardson GP, Kelley MW, Germain DL, Galton VA, Forrest D (2004) Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase. Proc Natl Acad Sci USA 101:3474–3479

    Article  PubMed  CAS  Google Scholar 

  160. Galton VA, Wood ET, St Germain EA, Withrow CA, Aldrich G, St Germain GM, Clark AS, St Germain DL (2007) Thyroid hormone homeostasis and action in the type 2 deiodinase-deficient rodent brain during development. Endocrinology 148:3080–3088

    Article  PubMed  CAS  Google Scholar 

  161. Galton VA, Schneider MJ, Clark AS, St Germain DL (2009) Life without T4 to T3 conversion: Studies in mice devoid of the 5’-deiodinases. Endocrinology doi:10.1210/en.2008-1572

  162. Vanderpas J (2006) Nutritional epidemiology and thyroid hormone metabolism. Annu Rev Nutr 26:293–322

    Article  PubMed  CAS  Google Scholar 

  163. Dumitrescu AM, Liao XH, Abdullah MS, Lado-Abeal J, Majed FA, Moeller LC, Boran G, Schomburg L, Weiss RE, Refetoff S (2005) Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat Genet 37:1247–1252

    Article  PubMed  CAS  Google Scholar 

  164. Novoselov SV, Kryukov GV, Xu XM, Carlson BA, Hatfield DL, Gladyshev VN (2007) Selenoprotein H is a nucleolar thioredoxin-like protein with a unique expression pattern. J Biol Chem 282:11960–11968

    Article  PubMed  CAS  Google Scholar 

  165. Morozova N, Forry EP, Shahid E, Zavacki AM, Harney JW, Kraytsberg Y, Berry MJ (2003) Antioxidant function of a novel selenoprotein in Drosophila melanogaster. Genes Cells 8:963–971

    Article  PubMed  CAS  Google Scholar 

  166. Panee J, Stoytcheva ZR, Liu W, Berry MJ (2007) Selenoprotein H is a redox-sensing high mobility group family DNA-binding protein that up-regulates genes involved in glutathione synthesis and phase II detoxification. J Biol Chem 282:23759–23765

    Article  PubMed  CAS  Google Scholar 

  167. Horibata Y, Hirabayashi Y (2007) Identification and characterization of human ethanolaminephosphotransferase1. J Lipid Res 48:503–508

    Article  PubMed  CAS  Google Scholar 

  168. Lu C, Qiu F, Zhou H, Peng Y, Hao W, Xu J, Yuan J, Wang S, Qiang B, Xu C, Peng X (2006) Identification and characterization of selenoprotein K: an antioxidant in cardiomyocytes. FEBS Lett 580:5189–5197

    Article  PubMed  CAS  Google Scholar 

  169. Chen CL, Shim MS, Chung J, Yoo HS, Ha JM, Kim JY, Choi J, Zang SL, Hou X, Carlson BA, Hatfield DL, Lee BJ (2006) G-rich, a Drosophila selenoprotein, is a Golgi-resident type III membrane protein. Biochem Biophys Res Commun 348:1296–1301

    Article  PubMed  CAS  Google Scholar 

  170. Labunskyy VM, Hatfield DL, Gladyshev VN (2007) The Sep15 protein family: roles in disulfide bond formation and quality control in the endoplasmic reticulum. IUBMB Life 59:1–5

    Article  PubMed  CAS  Google Scholar 

  171. Ferguson AD, Labunskyy VM, Fomenko DE, Arac D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J (2006) NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family. J Biol Chem 281:3536–3543

    Article  PubMed  CAS  Google Scholar 

  172. Korotkov KV, Kumaraswamy E, Zhou Y, Hatfield DL, Gladyshev VN (2001) Association between the 15-kDa selenoprotein and UDP-glucose: glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells. J Biol Chem 276:15330–15336

    Article  PubMed  CAS  Google Scholar 

  173. Labunskyy VM, Ferguson AD, Fomenko DE, Chelliah Y, Hatfield DL, Gladyshev VN (2005) A novel cysteine-rich domain of Sep15 mediates the interaction with UDP-glucose: glycoprotein glucosyltransferase. J Biol Chem 280:37839–37845

    Article  PubMed  CAS  Google Scholar 

  174. Hwang DY, Sin JS, Kim MS, Yim SY, Kim YK, Kim CK, Kim BG, Shim SB, Jee SW, Lee SH, Bae CJ, Lee BC, Jang MK, Cho JS, Chae KR (2008) Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat. Int J Mol Med 21:169–179

    PubMed  CAS  Google Scholar 

  175. Apostolou S, Klein JO, Mitsuuchi Y, Shetler JN, Poulikakos PI, Jhanwar SC, Kruger WD, Testa JR (2004) Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype. Oncogene 23:5032–5040

    Article  PubMed  CAS  Google Scholar 

  176. Kumaraswamy E, Malykh A, Korotkov KV, Kozyavkin S, Hu Y, Kwon SY, Moustafa ME, Carlson BA, Berry MJ, Lee BJ, Hatfield DL, Diamond AM, Gladyshev VN (2000) Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. J Biol Chem 275:35540–35547

    Article  PubMed  CAS  Google Scholar 

  177. Jablonska E, Gromadzinska J, Sobala W, Reszka E, Wasowicz W (2008) Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism. Eur J Nutr 47:47–54

    Article  PubMed  CAS  Google Scholar 

  178. Petit N, Lescure A, Rederstorff M, Krol A, Moghadaszadeh B, Wewer UM, Guicheney P (2003) Selenoprotein N: an endoplasmic reticulum glycoprotein with an early developmental expression pattern. Hum Mol Genet 12:1045–1053

    Article  PubMed  CAS  Google Scholar 

  179. Moghadaszadeh B, Petit N, Jaillard C, Brockington M, Roy SQ, Merlini L, Romero N, Estournet B, Desguerre I, Chaigne D, Muntoni F, Topaloglu H, Guicheney P (2001) Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Nat Genet 29:17–18

    Article  PubMed  CAS  Google Scholar 

  180. Flanigan KM, Kerr L, Bromberg MB, Leonard C, Tsuruda J, Zhang P, Gonzalez-Gomez I, Cohn R, Campbell KP, Leppert M (2000) Congenital muscular dystrophy with rigid spine syndrome: a clinical, pathological, radiological, and genetic study. Ann Neurol 47:152–161

    Article  PubMed  CAS  Google Scholar 

  181. Ferreiro A, Quijano-Roy S, Pichereau C, Moghadaszadeh B, Goemans N, Bonnemann C, Jungbluth H, Straub V, Villanova M, Leroy JP, Romero NB, Martin JJ, Muntoni F, Voit T, Estournet B, Richard P, Fardeau M, Guicheney P (2002) Mutations of the selenoprotein N gene, which is implicated in rigid spine muscular dystrophy, cause the classical phenotype of multiminicore disease: reassessing the nosology of early-onset myopathies. Am J Hum Genet 71:739–749

    Article  PubMed  Google Scholar 

  182. Ferreiro A, Ceuterick-de Groote C, Marks JJ, Goemans N, Schreiber G, Hanefeld F, Fardeau M, Martin JJ, Goebel HH, Richard P, Guicheney P, Bonnemann CG (2004) Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene. Ann Neurol 55:676–686

    Article  PubMed  CAS  Google Scholar 

  183. Clarke NF, Kidson W, Quijano-Roy S, Estournet B, Ferreiro A, Guicheney P, Manson JI, Kornberg AJ, Shield LK, North KN (2006) SEPN1: associated with congenital fiber-type disproportion and insulin resistance. Ann Neurol 59:546–552

    Article  PubMed  CAS  Google Scholar 

  184. Allamand V, Richard P, Lescure A, Ledeuil C, Desjardin D, Petit N, Gartioux C, Ferreiro A, Krol A, Pellegrini N, Urtizberea JA, Guicheney P (2006) A single homozygous point mutation in a 3′untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy. EMBO Rep 7:450–454

    PubMed  CAS  Google Scholar 

  185. Jurynec MJ, Xia R, Mackrill JJ, Gunther D, Crawford T, Flanigan KM, Abramson JJ, Howard MT, Grunwald DJ (2008) Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle. Proc Natl Acad Sci USA 105:12485–12490

    Article  PubMed  Google Scholar 

  186. Fomenko DE, Gladyshev VN (2002) CxxS: fold-independent redox motif revealed by genome-wide searches for thiol/disulfide oxidoreductase function. Protein Sci 11:2285–2296

    Article  PubMed  CAS  Google Scholar 

  187. Saito Y, Takahashi K (2002) Characterization of selenoprotein P as a selenium supply protein. Eur J Biochem 269:5746–5751

    Article  PubMed  CAS  Google Scholar 

  188. Hill KE, Zhou J, McMahan WJ, Motley AK, Atkins JF, Gesteland RF, Burk RF (2003) Deletion of selenoprotein P alters distribution of selenium in the mouse. J Biol Chem 278:13640–13646

    Article  PubMed  CAS  Google Scholar 

  189. Schomburg L, Schweizer U, Holtmann B, Flohe L, Sendtner M, Kohrle J (2003) Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues. Biochem J 370:397–402

    Article  PubMed  CAS  Google Scholar 

  190. Schweizer U, Streckfuss F, Pelt P, Carlson BA, Hatfield DL, Kohrle J, Schomburg L (2005) Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply. Biochem J 386:221–226

    Article  PubMed  CAS  Google Scholar 

  191. Shigeta K, Matsumura K, Suzuki Y, Shinohara A, Furuta N (2008) Distribution and dynamic pathway of selenium species in selenium-deficient mice injected with (82) Se-enriched selenite. Anal Sci 24:1117–1122

    Article  PubMed  CAS  Google Scholar 

  192. Valentine WM, Abel TW, Hill KE, Austin LM, Burk RF (2008) Neurodegeneration in mice resulting from loss of functional selenoprotein P or its receptor apolipoprotein E receptor 2. J Neuropathol Exp Neurol 67:68–77

    Article  PubMed  Google Scholar 

  193. Olson GE, Winfrey VP, Nagdas SK, Hill KE, Burk RF (2007) Apolipoprotein E receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis. J Biol Chem 282:12290–12297

    Article  PubMed  CAS  Google Scholar 

  194. Olson GE, Winfrey VP, Hill KE, Burk RF (2008) Megalin mediates selenoprotein P uptake by kidney proximal tubule epithelial cells. J Biol Chem 283:6854–6860

    Article  PubMed  CAS  Google Scholar 

  195. Saito Y, Hayashi T, Tanaka A, Watanabe Y, Suzuki M, Saito E, Takahashi K (1999) Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein P. J Biol Chem 274:2866–2871

    Article  PubMed  CAS  Google Scholar 

  196. Arteel GE, Mostert V, Oubrahim H, Briviba K, Abel J, Sies H (1998) Protection by selenoprotein P in human plasma against peroxynitrite-mediated oxidation and nitration. Biol Chem 379:1201–1205

    PubMed  CAS  Google Scholar 

  197. Bosschaerts T, Guilliams M, Noel W, Herin M, Burk RF, Hill KE, Brys L, Raes G, Ghassabeh GH, De Baetselier P, Beschin A (2008) Alternatively activated myeloid cells limit pathogenicity associated with African trypanosomiasis through the IL-10 inducible gene selenoprotein P. J Immunol 180:6168–6175

    PubMed  CAS  Google Scholar 

  198. Bellinger FP, He QP, Bellinger MT, Lin Y, Raman AV, White LR, Berry MJ (2008) Association of selenoprotein p with Alzheimer’s pathology in human cortex. J Alzheimers Dis 15:465–472

    PubMed  CAS  Google Scholar 

  199. Renko K, Hofmann PJ, Stoedter M, Hollenbach B, Behrends T, Kohrle J, Schweizer U, Schomburg L (2009) Down-regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice. FASEB J 10.1096/fj.08-119370

  200. Hollenbach B, Morgenthaler NG, Struck J, Alonso C, Bergmann A, Kohrle J, Schomburg L (2008) New assay for the measurement of selenoprotein P as a sepsis biomarker from serum. J Trace Elem Med Biol 22:24–32

    Article  PubMed  CAS  Google Scholar 

  201. Johtatsu T, Andoh A, Kurihara M, Iwakawa H, Tsujikawa T, Kashiwagi A, Fujiyama Y, Sasaki M (2007) Serum concentrations of trace elements in patients with Crohn’s disease receiving enteral nutrition. J Clin Biochem Nutr 41:197–201

    Article  PubMed  CAS  Google Scholar 

  202. Renko K, Werner M, Renner-Muller I, Cooper TG, Yeung CH, Hollenbach B, Scharpf M, Kohrle J, Schomburg L, Schweizer U (2008) Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. Biochem J 409:741–749

    Article  PubMed  CAS  Google Scholar 

  203. Cooper ML, Adami HO, Gronberg H, Wiklund F, Green FR, Rayman MP (2008) Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk. Cancer Res 68:10171–10177

    Article  PubMed  CAS  Google Scholar 

  204. Calvo A, Xiao N, Kang J, Best CJ, Leiva I, Emmert-Buck MR, Jorcyk C, Green JE (2002) Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors. Cancer Res 62:5325–5335

    PubMed  CAS  Google Scholar 

  205. Falnoga I, Tusek-Znidaric M (2007) Selenium–mercury interactions in man and animals. Biol Trace Elem Res 119:212–220

    Article  PubMed  CAS  Google Scholar 

  206. Kim HY, Gladyshev VN (2007) Methionine sulfoxide reductases: selenoprotein forms and roles in antioxidant protein repair in mammals. Biochem J 407:321–329

    Article  PubMed  CAS  Google Scholar 

  207. Kim HY, Fomenko DE, Yoon YE, Gladyshev VN (2006) Catalytic advantages provided by selenocysteine in methionine-S-sulfoxide reductases. Biochemistry 45:13697–13704

    Article  PubMed  CAS  Google Scholar 

  208. Lee TH, Kim HY (2008) An anaerobic bacterial MsrB model reveals catalytic mechanisms, advantages, and disadvantages provided by selenocysteine and cysteine in reduction of methionine-R-sulfoxide. Arch Biochem Biophys 478:175–180

    Article  PubMed  CAS  Google Scholar 

  209. Fomenko DE, Novoselov SV, Natarajan SK, Lee BC, Koc A, Carlson BA, Lee TH, Kim HY, Hatfield DL, Gladyshev VN (2008) Methionine-R-sulfoxide reductase 1 (MsrB1) knockout Mmice: roles of MsrB1 in redox regulation and identification of a novel selenoprotein form. J Biol Chem 284:5986–5993

    Article  PubMed  CAS  Google Scholar 

  210. Hansel A, Heinemann SH, Hoshi T (2005) Heterogeneity and function of mammalian MSRs: enzymes for repair, protection and regulation. Biochim Biophys Acta 1703:239–247

    PubMed  CAS  Google Scholar 

  211. Stadtman ER (2006) Protein oxidation and aging. Free Radic Res 40:1250–1258

    Article  PubMed  CAS  Google Scholar 

  212. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O’Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, Anderson ME (2008) A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133:462–474

    Article  PubMed  CAS  Google Scholar 

  213. Ye Y, Shibata Y, Yun C, Ron D, Rapoport TA (2004) A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429:841–847

    Article  PubMed  CAS  Google Scholar 

  214. Gao Y, Feng HC, Walder K, Bolton K, Sunderland T, Bishara N, Quick M, Kantham L, Collier GR (2004) Regulation of the selenoprotein SelS by glucose deprivation and endoplasmic reticulum stress: SelS is a novel glucose-regulated protein. FEBS Lett 563:185–190

    Article  PubMed  CAS  Google Scholar 

  215. Gao Y, Pagnon J, Feng HC, Konstantopolous N, Jowett JB, Walder K, Collier GR (2007) Secretion of the glucose-regulated selenoprotein SEPS1 from hepatoma cells. Biochem Biophys Res Commun 356:636–641

    Article  PubMed  CAS  Google Scholar 

  216. Curran JE, Jowett JB, Elliott KS, Gao Y, Gluschenko K, Wang J, Abel Azim DM, Cai G, Mahaney MC, Comuzzie AG, Dyer TD, Walder KR, Zimmet P, MacCluer JW, Collier GR, Kissebah AH, Blangero J (2005) Genetic variation in selenoprotein S influences inflammatory response. Nat Genet 37:1234–1241

    Article  PubMed  CAS  Google Scholar 

  217. Kim KH, Gao Y, Walder K, Collier GR, Skelton J, Kissebah AH (2007) SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced apoptosis. Biochem Biophys Res Commun 354:127–132

    Article  PubMed  CAS  Google Scholar 

  218. Alanne M, Kristiansson K, Auro K, Silander K, Kuulasmaa K, Peltonen L, Salomaa V, Perola M (2007) Variation in the selenoprotein S gene locus is associated with coronary heart disease and ischemic stroke in two independent Finnish cohorts. Hum Genet 122:355–365

    Article  PubMed  CAS  Google Scholar 

  219. Silander K, Alanne M, Kristiansson K, Saarela O, Ripatti S, Auro K, Karvanen J, Kulathinal S, Niemela M, Ellonen P, Vartiainen E, Jousilahti P, Saarela J, Kuulasmaa K, Evans A, Perola M, Salomaa V, Peltonen L (2008) Gender differences in genetic risk profiles for cardiovascular disease. PLoS ONE 3:e3615

    Article  PubMed  CAS  Google Scholar 

  220. Moses EK, Johnson MP, Tommerdal L, Forsmo S, Curran JE, Abraham LJ, Charlesworth JC, Brennecke SP, Blangero J, Austgulen R (2008) Genetic association of preeclampsia to the inflammatory response gene SEPS1. Am J Obstet Gynecol 198(336):e331–e335

    Google Scholar 

  221. Marinou I, Walters K, Dickson MC, Binks MH, Bax DE, Wilson AG (2008) Evidence of epistasis between Interleukin-1 and Selenoprotein-S with susceptibility to RA. Ann Rheum Dis doi:10.1136/ard.2008.090001

  222. Shibata T, Arisawa T, Tahara T, Ohkubo M, Yoshioka D, Maruyama N, Fujita H, Kamiya Y, Nakamura M, Nagasaka M, Iwata M, Takahama K, Watanabe M, Hirata I (2009) Selenoprotein S (SEPS1) gene-105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population. BMC Gastroenterol 9:2

    Article  PubMed  CAS  Google Scholar 

  223. Martinez A, Santiago JL, Varade J, Marquez A, Lamas JR, Mendoza JL, de la Calle H, Diaz-Rubio M, de la Concha EG, Fernandez-Gutierrez B, Urcelay E (2008) Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases. BMC Genomics 9:329

    Article  PubMed  CAS  Google Scholar 

  224. Grumolato L, Ghzili H, Montero-Hadjadje M, Gasman S, Lesage J, Tanguy Y, Galas L, Ait-Ali D, Leprince J, Guerineau NC, Elkahloun AG, Fournier A, Vieau D, Vaudry H, Anouar Y (2008) Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca2+mobilization and neuroendocrine secretion. FASEB J 22:1756–1768

    Article  PubMed  CAS  Google Scholar 

  225. Dikiy A, Novoselov SV, Fomenko DE, Sengupta A, Carlson BA, Cerny RL, Ginalski K, Grishin NV, Hatfield DL, Gladyshev VN (2007) SelT, SelW, SelH, and Rdx12: genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family. Biochemistry 46:6871–6882

    Article  PubMed  CAS  Google Scholar 

  226. Gu QP, Sun Y, Ream LW, Whanger PD (2000) Selenoprotein W accumulates primarily in primate skeletal muscle, heart, brain and tongue. Mol Cell Biochem 204:49–56

    Article  PubMed  CAS  Google Scholar 

  227. Yeh JY, Beilstein MA, Andrews JS, Whanger PD (1995) Tissue distribution and influence of selenium status on levels of selenoprotein W. FASEB J 9:392–396

    PubMed  CAS  Google Scholar 

  228. Pagmantidis V, Bermano G, Villette S, Broom I, Arthur J, Hesketh J (2005) Effects of Se-depletion on glutathione peroxidase and selenoprotein W gene expression in the colon. FEBS Lett 579:792–796

    Article  PubMed  CAS  Google Scholar 

  229. Beilstein MA, Vendeland SC, Barofsky E, Jensen ON, Whanger PD (1996) Selenoprotein W of rat muscle binds glutathione and an unknown small molecular weight moiety. J Inorg Biochem 61:117–124

    Article  PubMed  CAS  Google Scholar 

  230. Loflin J, Lopez N, Whanger PD, Kioussi C (2006) Selenoprotein W during development and oxidative stress. J Inorg Biochem 100:1679–1684

    Article  PubMed  CAS  Google Scholar 

  231. Aachmann FL, Fomenko DE, Soragni A, Gladyshev VN, Dikiy A (2007) Solution structure of selenoprotein W and NMR analysis of its interaction with 14-3-3 proteins. J Biol Chem 282:37036–37044

    Article  PubMed  CAS  Google Scholar 

  232. Kim IY, Stadtman TC (1995) Selenophosphate synthetase: detection in extracts of rat tissues by immunoblot assay and partial purification of the enzyme from the Archaean Methanococcus vannielii. Proc Natl Acad Sci USA 92:7710–7713

    Article  PubMed  CAS  Google Scholar 

  233. Low SC, Harney JW, Berry MJ (1995) Cloning and functional characterization of human selenophosphate synthetase, an essential component of selenoprotein synthesis. J Biol Chem 270:21659–21664

    Article  PubMed  CAS  Google Scholar 

  234. Guimaraes MJ, Peterson D, Vicari A, Cocks BG, Copeland NG, Gilbert DJ, Jenkins NA, Ferrick DA, Kastelein RA, Bazan JF, Zlotnik A (1996) Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is there an autoregulatory mechanism in selenocysteine metabolism? Proc Natl Acad Sci USA 93:15086–15091

    Article  PubMed  CAS  Google Scholar 

  235. Tamura T, Yamamoto S, Takahata M, Sakaguchi H, Tanaka H, Stadtman TC, Inagaki K (2004) Selenophosphate synthetase genes from lung adenocarcinoma cells: Sps1 for recycling l-selenocysteine and Sps2 for selenite assimilation. Proc Natl Acad Sci USA 101:16162–16167

    Article  PubMed  CAS  Google Scholar 

  236. Lobanov AV, Hatfield DL, Gladyshev VN (2008) Selenoproteinless animals: selenophosphate synthetase SPS1 functions in a pathway unrelated to selenocysteine biosynthesis. Protein Sci 17:176–182

    Article  PubMed  CAS  Google Scholar 

  237. Xu XM, Carlson BA, Irons R, Mix H, Zhong N, Gladyshev VN, Hatfield DL (2007) Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis. Biochem J 404:115–120

    Article  PubMed  CAS  Google Scholar 

  238. Furumiya K, Kanaya K, Tanabe K, Tanaka Y, Mizutani T (2008) Active bovine selenophosphate synthetase 2, not having selenocysteine. Mol Biol Rep 35:541–549

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by NIH/NCRR grants G12RR003061 and P20RR016453.

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  1. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI, 96813, USA

    M. A. Reeves & P. R. Hoffmann

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Reeves, M.A., Hoffmann, P.R. The human selenoproteome: recent insights into functions and regulation. Cell. Mol. Life Sci. 66, 2457–2478 (2009). https://doi.org/10.1007/s00018-009-0032-4

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