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Selenium and Selenoproteins in Neuroprotection and Neuronal Cell Death

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Book cover Metal Ion in Stroke

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Significant progress has taken place in the field of selenium neurobiology since the discovery of selenocysteine as the 21st genetically coded amino acid. Twenty-five selenoproteins playing important roles in various processes of redox signalling have been identified in the human genome to date, which is why these proteins are also called selenoenzymes. The function of all selenoproteins is dictated by the trace element selenium. Its depletion is therefore detrimental to selenoprotein activity, leading to increased oxidative stress and adversely affecting neuronal cell survival. Oxidative stress constitutes one of the underlying pathological processes in acute neurodegenerative diseases such as stroke and epilepsy, as well as in chronic processes such as Parkinson’s and Alzheimer’s diseases. Selenium, as well as many selenoproteins like glutathione peroxidases (GPx), thioredoxin reductases and selenoprotein M are involved in antioxidant defence and the maintenance of intracellular redox balance. Research in molecular biology and gene targeting in mice has led to the discovery of the essential role of selenoproteins in neuronal cell functioning. The available data on selenium and selenoproteins with regard to neuronal cell death are summarized and potential therapeutic targets in neuroprotective approaches in conditions of human disease discussed.

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References

  • al-Deeb S, al-Moutaery K et al (1995) Neuroprotective effect of selenium on iminodipropionitrile-induced toxicity. J Psychiatry Neurosci 20(3):189–192

    PubMed  CAS  Google Scholar 

  • Ashton K, Hooper L et al (2009) Methods of assessment of selenium status in humans: a systematic review. Am J Clin Nutr 89(6):2025S–2039S

    Article  PubMed  CAS  Google Scholar 

  • Bellinger FP, He QP et al (2008) Association of selenoprotein p with Alzheimer’s pathology in human cortex. J Alzheimers Dis 15(3):465–472

    PubMed  CAS  Google Scholar 

  • Berry MJ, Banu L et al (1991) Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3′ untranslated region. Nature 353(6341):273–276

    Article  PubMed  CAS  Google Scholar 

  • Birringer M, Pilawa S et al (2002) Trends in selenium biochemistry. Nat Prod Rep 19(6):693–718

    Article  PubMed  CAS  Google Scholar 

  • Bol GF, Jurrmann N et al (2003) Recruitment of the interleukin-1 receptor (IL-1RI)-associated kinase IRAK to the IL-1RI is redox regulated. Biol Chem 384(4):609–617

    Article  PubMed  CAS  Google Scholar 

  • Brauer AU, Savaskan NE (2004) Molecular actions of selenium in the brain: neuroprotective mechanisms of an essential trace element. Rev Neurosci 15(1):19–32

    PubMed  Google Scholar 

  • Brigelius-Flohe R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27(9–10):951–965

    Article  PubMed  CAS  Google Scholar 

  • Brown MR, Cohen HJ et al (1986) Proximal muscle weakness and selenium deficiency associated with long term parenteral nutrition. Am J Clin Nutr 43(4):549–554

    PubMed  CAS  Google Scholar 

  • Burk RF, Gregory PE (1982) Some characteristics of 75Se-P, a selenoprotein found in rat liver and plasma, and comparison of it with selenoglutathione peroxidase. Arch Biochem Biophys 213(1):73–80

    Article  PubMed  CAS  Google Scholar 

  • Burk RF, Hill KE et al (1997) Selenoprotein P associates with endothelial cells in rat tissues. Histochem Cell Biol 108(1):11–15

    Article  PubMed  CAS  Google Scholar 

  • Carlson BA, Novoselov SV et al (2004) Specific excision of the selenocysteine tRNA[Ser]Sec (Trsp) gene in mouse liver demonstrates an essential role of selenoproteins in liver function. J Biol Chem 279(9):8011–8017

    Article  PubMed  CAS  Google Scholar 

  • Chan S, Kachilele S et al (2002) Early expression of thyroid hormone deiodinases and receptors in human fetal cerebral cortex. Brain Res Dev Brain Res 138(2):109–116

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Berry MJ (2003) Selenium and selenoproteins in the brain and brain diseases. J Neurochem 86(1):1–12

    Article  PubMed  CAS  Google Scholar 

  • Cone JE, Del Río RM, Davis JN, Stadtman TC (1976) Chemical characterization of the selenoprotein component of clostridial glycine reductase: identification of selenocysteine as the organoselenium moiety. Proc Natl Acad Sci USA 73(8):2659–2663

    Article  PubMed  CAS  Google Scholar 

  • Dalla Puppa L, Savaskan NE, Bräuer AU, Bene D, Kiriakopoulos A (2007) The role of selenite on microglial migration. Ann N Y Acad Sci 1096:179–183

    Article  PubMed  CAS  Google Scholar 

  • Damier P, Hirsch EC et al (1993) Glutathione peroxidase, glial cells and Parkinson’s disease. Neuroscience 52(1):1–6

    Article  PubMed  CAS  Google Scholar 

  • Dewhirst MW, Cao Y et al (2008) Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8(6):425–437

    Article  PubMed  CAS  Google Scholar 

  • Eyupoglu IY, Bechmann I et al (2003a) Modification of microglia function protects from lesion-induced neuronal alterations and promotes sprouting in the hippocampus. Faseb J 17(9):1110–1111

    PubMed  CAS  Google Scholar 

  • Eyupoglu IY, Savaskan NE et al (2003b) Identification of neuronal cell death in a model of degeneration in the hippocampus. Brain Res Brain Res Protoc 11(1):1–8

    Article  PubMed  Google Scholar 

  • Fagegaltier D, Hubert N et al (2000) Characterization of mSelB, a novel mammalian elongation factor for selenoprotein translation. Embo J 19(17):4796–4805

    Article  PubMed  CAS  Google Scholar 

  • Ferreiro A, Quijano-Roy S et al (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(4):739–749

    Article  PubMed  Google Scholar 

  • Flohe L, Gunzler WA et al (1973) Glutathione peroxidase: a selenoenzyme. FEBS Lett 32(1):132–134

    Article  PubMed  CAS  Google Scholar 

  • Grunblatt E, Mandel S et al (2000) MPTP and 6-hydroxydopamine-induced neurodegeneration as models for Parkinson’s disease: neuroprotective strategies. J Neurol 247(Suppl 2):II95–II102

    PubMed  Google Scholar 

  • Gu J, Royland JE et al (1997) Selenium is required for normal upregulation of myelin genes in differentiating oligodendrocytes. J Neurosci Res 47(6):626–635

    Article  PubMed  CAS  Google Scholar 

  • Guimaraes MJ, Peterson D et al (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(26):15086–15091

    Article  PubMed  CAS  Google Scholar 

  • Haapasalo H, Kylaniemi M et al (2003) Expression of antioxidant enzymes in astrocytic brain tumors. Brain Pathol 13(2):155–164

    Article  PubMed  CAS  Google Scholar 

  • Hansson HA, Holmgren A et al (1989) Changes in the distribution of insulin-like growth factor I, thioredoxin, thioredoxin reductase and ribonucleotide reductase during the development of the retina. Exp Eye Res 48(3):411–420

    Article  PubMed  CAS  Google Scholar 

  • Hatfield DL, Gladyshev VN (2002) How selenium has altered our understanding of the genetic code. Mol Cell Biol 22(11):3565–3576

    Article  PubMed  CAS  Google Scholar 

  • Hill KE, McCollum GW et al (1997) Thioredoxin reductase activity is decreased by selenium deficiency. Biochem Biophys Res Commun 234(2):293–295

    Article  PubMed  CAS  Google Scholar 

  • Hubert N, Walczak R et al (1996) A protein binds the selenocysteine insertion element in the 3′-UTR of mammalian selenoprotein mRNAs. Nucleic Acids Res 24(3):464–469

    Article  PubMed  CAS  Google Scholar 

  • Imam SZ, Newport GD et al (1999) Selenium, an antioxidant, protects against methamphetamine-induced dopaminergic neurotoxicity. Brain Res 818(2):575–578

    Article  PubMed  CAS  Google Scholar 

  • Jarvela S, Bragge H et al (2006) Antioxidant enzymes in oligodendroglial brain tumors: association with proliferation, apoptotic activity and survival. J Neurooncol 77(2):131–140

    Article  PubMed  Google Scholar 

  • Kien CL, Ganther HE (1983) Manifestations of chronic selenium deficiency in a child receiving total parenteral nutrition. Am J Clin Nutr 37(2):319–328

    PubMed  CAS  Google Scholar 

  • Kim HC, Jhoo WK et al (1999) Protection of methamphetamine nigrostriatal toxicity by dietary selenium. Brain Res 851(1–2):76–86

    Article  PubMed  CAS  Google Scholar 

  • Kim H, Jhoo W et al (2000) Selenium deficiency potentiates methamphetamine-induced nigral neuronal loss; comparison with MPTP model. Brain Res 862(1–2):247–252

    Article  PubMed  CAS  Google Scholar 

  • Klein EA, Lippman SM et al (2003) The selenium and vitamin E cancer prevention trial. World J Urol 21(1):21–27

    PubMed  CAS  Google Scholar 

  • Kryukov GV, Kumar RA et al (2002) Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase. Proc Natl Acad Sci USA 99(7):4245–4250

    Article  PubMed  CAS  Google Scholar 

  • Kryukov GV, Castellano S et al (2003) Characterization of mammalian selenoproteomes. Science 300(5624):1439–1443

    Article  PubMed  CAS  Google Scholar 

  • Lee BJ, Worland PJ et al (1989) Identification of a selenocysteyl-tRNA(Ser) in mammalian cells that recognizes the nonsense codon, UGA. J Biol Chem 264(17):9724–9727

    PubMed  CAS  Google Scholar 

  • Leist M, Raab B et al (1996) Conventional cell culture media do not adequately supply cells with antioxidants and thus facilitate peroxide-induced genotoxicity. Free Radic Biol Med 21(3):297–306

    Article  PubMed  CAS  Google Scholar 

  • Lippman SM, Klein EA et al (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(1):39–51

    Article  PubMed  CAS  Google Scholar 

  • Loef M, Schrauzer GN, Walach H (2011) Selenium and Alzheimer’s disease: a meta-analysis. J Alzheimers Dis 26(1):81–104, May 13 epub

    PubMed  CAS  Google Scholar 

  • Lovell MA, Xie C et al (2000) Decreased thioredoxin and increased thioredoxin reductase levels in Alzheimer’s disease brain. Free Radic Biol Med 28(3):418–427

    Article  PubMed  CAS  Google Scholar 

  • Low SC, Grundner-Culemann E et al (2000) SECIS-SBP2 interactions dictate selenocysteine incorporation efficiency and selenoprotein hierarchy. EMBO J 19(24):6882–6890

    Article  PubMed  CAS  Google Scholar 

  • McCann JC, Ames BN (2011) Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. FASEB J 25(6):1793–1814

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JH, Nicol F et al (1998) Selenoprotein expression and brain development in preweanling selenium- and iodine-deficient rats. J Mol Endocrinol 20(2):203–210

    Article  PubMed  CAS  Google Scholar 

  • Moghadaszadeh B, Petit N et al (2001) Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Nat Genet 29(1):17–18

    Article  PubMed  CAS  Google Scholar 

  • Moos PJ, Edes K et al (2003) Electrophilic prostaglandins and lipid aldehydes repress redox-sensitive transcription factors p53 and hypoxia-inducible factor by impairing the selenoprotein thioredoxin reductase. J Biol Chem 278(2):745–750

    Article  PubMed  CAS  Google Scholar 

  • Moskovitz J, Stadtman ER (2003) Selenium-deficient diet enhances protein oxidation and affects methionine sulfoxide reductase (MsrB) protein level in certain mouse tissues. Proc Natl Acad Sci USA 100(13):7486–7490

    Article  PubMed  CAS  Google Scholar 

  • Moskovitz J, Jenkins NA et al (1996) Chromosomal localization of the mammalian peptide-methionine sulfoxide reductase gene and its differential expression in various tissues. Proc Natl Acad Sci USA 93(8):3205–3208

    Article  PubMed  CAS  Google Scholar 

  • Moskovitz J, Bar-Noy S et al (2001) Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. Proc Natl Acad Sci USA 98(23):12920–12925

    Article  PubMed  CAS  Google Scholar 

  • Moskovitz J, Singh VK et al (2002) Purification and characterization of methionine sulfoxide reductases from mouse and Staphylococcus aureus and their substrate stereospecificity. Biochem Biophys Res Commun 290(1):62–65

    Article  PubMed  CAS  Google Scholar 

  • Motsenbocker MA, Tappel AL (1982) Selenium and selenoproteins in the rat kidney. Biochim Biophys Acta 709(2):160–165

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Olson GE, Winfrey VP et al (2008) Megalin mediates selenoprotein P uptake by kidney proximal tubule epithelial cells. J Biol Chem 283(11):6854–6860

    Article  PubMed  CAS  Google Scholar 

  • Oztas B, Kilic S et al (2001) Influence of antioxidants on the blood-brain barrier permeability during epileptic seizures. J Neurosci Res 66(4):674–678

    Article  PubMed  CAS  Google Scholar 

  • Ramaekers VT, Calomme M et al (1994) Selenium deficiency triggering intractable seizures. Neuropediatrics 25(4):217–223

    Article  PubMed  CAS  Google Scholar 

  • Rayman MP (2009) Selenoproteins and human health: insights from epidemiological data. Biochim Biophys Acta 1790(11):1533–1540

    Article  PubMed  CAS  Google Scholar 

  • Reeves MA, Hoffmann PR (2009) The human selenoproteome: recent insights into functions and regulation. Cell Mol Life Sci 66(15):2457–2478

    Article  PubMed  CAS  Google Scholar 

  • Rotruck JT, Pope AL et al (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179(73):588–590

    Article  PubMed  CAS  Google Scholar 

  • Ruan H, Tang XD et al (2002) High-quality life extension by the enzyme peptide methionine sulfoxide reductase. Proc Natl Acad Sci USA 99(5):2748–2753

    Article  PubMed  CAS  Google Scholar 

  • Rubin JJ, Willmore LJ (1980) Prevention of iron-induced epileptiform discharges in rats by treatment with antiperoxidants. Exp Neurol 67(3):472–480

    Article  PubMed  CAS  Google Scholar 

  • Saijoh K, Saito N et al (1995) Molecular cloning of cDNA encoding a bovine selenoprotein P-like protein containing 12 selenocysteines and a (His-Pro) rich domain insertion, and its regional expression. Brain Res Mol Brain Res 30(2):301–311

    Article  PubMed  CAS  Google Scholar 

  • Saito Y, Takahashi K (2002) Characterization of selenoprotein P as a selenium supply protein. Eur J Biochem 269(22):5746–5751

    Article  PubMed  CAS  Google Scholar 

  • Sanchez V, Zeini M et al (2003) The nNOS inhibitor, AR-R17477AR, prevents the loss of NF68 immunoreactivity induced by methamphetamine in the mouse striatum. J Neurochem 85(2):515–524

    Article  PubMed  CAS  Google Scholar 

  • Savaskan NE, Brauer AU et al (2003) Selenium deficiency increases susceptibility to glutamate-induced excitotoxicity. FASEB J 17(1):112–114

    PubMed  CAS  Google Scholar 

  • Savaskan NE, Borchert A et al (2007a) Role for glutathione peroxidase-4 in brain development and neuronal apoptosis: specific induction of enzyme expression in reactive astrocytes following brain injury. Free Radic Biol Med 43(2):191–201

    Article  PubMed  CAS  Google Scholar 

  • Savaskan NE, Ufer C et al (2007b) Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function. Biol Chem 388(10):1007–1017

    Article  PubMed  CAS  Google Scholar 

  • Schomburg L, Schweizer U et al (2003) Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues. Biochem J 370(Pt 2):397–402

    Article  PubMed  CAS  Google Scholar 

  • Schwarz K, Foltz CM (1999) Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. 1951. Nutrition 15(3):255

    PubMed  CAS  Google Scholar 

  • Schweizer U, Michaelis M et al (2004) Efficient selenium transfer from mother to offspring in selenoprotein-P-deficient mice enables dose-dependent rescue of phenotypes associated with selenium deficiency. Biochem J 378(Pt 1):21–26

    Article  PubMed  CAS  Google Scholar 

  • Sian J, Gerlach M et al (1999) Parkinson’s disease: a major hypokinetic basal ganglia disorder. J Neural Transm 106(5–6):443–476

    Article  PubMed  CAS  Google Scholar 

  • Stadtman TC (1996) Selenocysteine. Annu Rev Biochem 65:83–100

    Article  PubMed  CAS  Google Scholar 

  • Takizawa S, Matsushima K et al (1994) Immunohistochemical localization of glutathione peroxidase in infarcted human brain. J Neurol Sci 122(1):66–73

    Article  PubMed  CAS  Google Scholar 

  • Trepanier G, Furling D et al (1996) Immunocytochemical localization of seleno-glutathione peroxidase in the adult mouse brain. Neuroscience 75(1):231–243

    Article  PubMed  CAS  Google Scholar 

  • Tujebajeva RM, Copeland PR et al (2000) Decoding apparatus for eukaryotic selenocysteine insertion. EMBO Rep 1(2):158–163

    Article  PubMed  CAS  Google Scholar 

  • van Eersel J, Ke YD et al (2010) Sodium selenate mitigates tau pathology, neurodegeneration, and functional deficits in Alzheimer’s disease models. Proc Natl Acad Sci USA 107(31):13888–13893

    Article  PubMed  Google Scholar 

  • Vural H, Demirin H et al (2010) Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer’s disease. J Trace Elem Med Biol 24(3):169–173

    Article  PubMed  CAS  Google Scholar 

  • Walther LE, Winnefeld K et al (2000) Determination of iron, copper, zinc, magnesium and selenium in plasma and erythrocytes in neurosurgical patients. J Trace Elem Med Biol 14(2):92–95

    Article  PubMed  CAS  Google Scholar 

  • Weber GF, Maertens P et al (1991) Glutathione peroxidase deficiency and childhood seizures. Lancet 337(8755):1443–1444

    Article  PubMed  CAS  Google Scholar 

  • Willmore LJ, Rubin JJ (1981) Antiperoxidant pretreatment and iron-induced epileptiform discharges in the rat: EEG and histopathologic studies. Neurology 31(1):63–69

    Article  PubMed  CAS  Google Scholar 

  • Yan J, Barrett JN (1998) Purification from bovine serum of a survival-promoting factor for cultured central neurons and its identification as selenoprotein-P. J Neurosci 18(21):8682–8691

    PubMed  CAS  Google Scholar 

  • Yang FY, Lin ZH et al (1988) Keshan disease—an endemic mitochondrial cardiomyopathy in China. J Trace Elem Electrolytes Health Dis 2(3):157–163

    PubMed  CAS  Google Scholar 

  • Yeo JE, Kim JH, Kang SK (2008) Selenium attenuates ROS-mediated apoptotic cell death of injured spinal cord through prevention of mitochondria dysfunction; in vitro and in vivo study. Cell Physiol Biochem 21(1–3):225–238

    Article  PubMed  CAS  Google Scholar 

  • Zafar KS, Siddiqui A et al (2003) Dose-dependent protective effect of selenium in rat model of Parkinson’s disease: neurobehavioral and neurochemical evidences. J Neurochem 84(3):438–446

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Zhou Y et al (2008) Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals. J Biol Chem 283(4):2427–2438

    Article  PubMed  CAS  Google Scholar 

  • Zhong L, Holmgren A (2000) Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. J Biol Chem 275(24):18121–18128

    Article  PubMed  CAS  Google Scholar 

  • Zhou BF, Stamler J et al (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(9):623–630

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, University Medical School Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Schwabachanlage 6, Erlangen, 91054, Germany

    Nic E. Savaskan, Nirjhar Hore & Ilker Y. Eyupoglu

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  1. Nic E. Savaskan
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  2. Nirjhar Hore
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  3. Ilker Y. Eyupoglu
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Correspondence to Nic E. Savaskan .

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  1. , Department of Biomedical Sciences, Ohio University, 346 Irvine Hall, Athens, 45701, Ohio, USA

    Yang V. Li

  2. Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, 92354, California, USA

    John H. Zhang

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Savaskan, N.E., Hore, N., Eyupoglu, I.Y. (2012). Selenium and Selenoproteins in Neuroprotection and Neuronal Cell Death. In: Li, Y., Zhang, J. (eds) Metal Ion in Stroke. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9663-3_25

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