Selenium, Selenoproteins, and Immunity

Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.

[1]  Michael Hagemann-Jensen,et al.  The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D* , 2014, The Journal of Biological Chemistry.

[2]  Hwa-young Kim The methionine sulfoxide reduction system: selenium utilization and methionine sulfoxide reductase enzymes and their functions. , 2013, Antioxidants & redox signaling.

[3]  B. Carlson,et al.  Selenoprotein Expression in Macrophages Is Critical for Optimal Clearance of Parasitic Helminth Nippostrongylus brasiliensis* , 2015, The Journal of Biological Chemistry.

[4]  W. Wurst,et al.  Essential Role for Mitochondrial Thioredoxin Reductase in Hematopoiesis, Heart Development, and Heart Function , 2004, Molecular and Cellular Biology.

[5]  B. Dworkin Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS). , 1994, Chemico-biological interactions.

[6]  Fukun W. Hoffmann,et al.  Dietary selenium modulates activation and differentiation of CD4+ T cells in mice through a mechanism involving cellular free thiols. , 2010, The Journal of nutrition.

[7]  V. Gladyshev,et al.  Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo , 2017, Scientific Reports.

[8]  Fukun W. Hoffmann,et al.  A Role for Dietary Selenium and Selenoproteins in Allergic Airway Inflammation1 , 2007, The Journal of Immunology.

[9]  P. Kang,et al.  Selenium, iodine, and the relation with Kashin-Beck disease. , 2011, Nutrition.

[10]  K. S. Prabhu,et al.  Selenium levels affect the IL-4-induced expression of alternative activation markers in murine macrophages. , 2011, The Journal of nutrition.

[11]  R. Burk,et al.  Selenoprotein P-expression, functions, and roles in mammals. , 2009, Biochimica et biophysica acta.

[12]  BoukhzarLoubna,et al.  Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease. , 2016 .

[13]  P. Hoffmann,et al.  The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. , 2012, Antioxidants & redox signaling.

[14]  Dietary reference values for food energy and nutrients for the United Kingdom. Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy. , 1991, Reports on health and social subjects.

[15]  K. S. Prabhu,et al.  Selenium and Selenoproteins in Gut Inflammation—A Review , 2018, Antioxidants.

[16]  M. Baum,et al.  Micronutrient status in relationship to mortality in HIV-1 disease. , 2009, Nutrition reviews.

[17]  C. Barbante,et al.  Selenium biochemistry and its role for human health. , 2014, Metallomics : integrated biometal science.

[18]  R. Brigelius-Flohé,et al.  Glutathione peroxidases in different stages of carcinogenesis. , 2009, Biochimica et biophysica acta.

[19]  L. M. Pereira,et al.  The treatment with selenium increases placental parasitismin pregnant Wistar rats infected with the Y strain of Trypanosoma cruzi. , 2018, Immunobiology.

[20]  S. Gygi,et al.  Selenoprotein S is involved in maintenance and transport of multiprotein complexes. , 2014, The Biochemical journal.

[21]  R. Brigelius-Flohé,et al.  Glutathione peroxidases and redox-regulated transcription factors , 2006, Biological chemistry.

[22]  M. Beck,et al.  Selenium deficiency and viral infection. , 2003, The Journal of nutrition.

[23]  Vincent Mutabazi,et al.  Effect of selenium supplementation on CD4+ T-cell recovery, viral suppression and morbidity of HIV-infected patients in Rwanda: a randomized controlled trial , 2015, AIDS.

[24]  R. Burk,et al.  Regulation of Selenium Metabolism and Transport. , 2015, Annual review of nutrition.

[25]  S. Marklund,et al.  Levels of selenium in plasma and glutathione peroxidase in erythrocytes and the risk of breast cancer , 1993, Biological Trace Element Research.

[26]  M. Faramarzi,et al.  Dose-response relationship study of selenium nanoparticles as an immunostimulatory agent in cancer-bearing mice. , 2015, Archives of medical research.

[27]  T. Rapoport,et al.  A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol , 2004, Nature.

[28]  S. Fan,et al.  Interleukin-8 serum levels in patients with hepatocellular carcinoma: correlations with clinicopathological features and prognosis. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[29]  H. Steinbrenner,et al.  Dietary selenium in adjuvant therapy of viral and bacterial infections. , 2015, Advances in nutrition.

[30]  L. Sokoloff Acquired chondronecrosis. , 1990, Annals of the rheumatic diseases.

[31]  Y. Hu,et al.  Selenium deficiency impairs host innate immune response and induces susceptibility to Listeria monocytogenes infection , 2009, BMC Immunology.

[32]  H. Ganther,et al.  Selenium: Biochemical Role as a Component of Glutathione Peroxidase , 1973, Science.

[33]  Wenyu Li,et al.  Selenium Plays a Protective Role in Staphylococcus aureus-Induced Endometritis in the Uterine Tissue of Rats , 2016, Biological Trace Element Research.

[34]  S. Gygi,et al.  Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins , 2018, Cell reports.

[35]  Z. Sepehri,et al.  Role of essential trace elements in tuberculosis infection: A review article. , 2017, The Indian journal of tuberculosis.

[36]  G. Nilsonne,et al.  Selenite Induces Posttranscriptional Blockade of HLA-E Expression and Sensitizes Tumor Cells to CD94/NKG2A-Positive NK Cells , 2011, The Journal of Immunology.

[37]  L. Flohé,et al.  Glutathione peroxidase: A selenoenzyme , 1973, FEBS letters.

[38]  P. Galan,et al.  Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. , 1999, Archives of internal medicine.

[39]  Gang Qian,et al.  The Hepatoprotective Effect of Selenium-Enriched Yeast and Gum Arabic Combination on Carbon Tetrachloride-Induced Chronic Liver Injury in Rats. , 2018, Journal of food science.

[40]  R. Burk,et al.  Evidence for intestinal release of absorbed selenium in a form with high hepatic extraction. , 1992, The American journal of physiology.

[41]  M. Mahdavi,et al.  Oral administration of synthetic selenium nanoparticles induced robust Th1 cytokine pattern after HBs antigen vaccination in mouse model. , 2017, Journal of infection and public health.

[42]  M. Berry,et al.  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* , 2007, Journal of Biological Chemistry.

[43]  C. Suetens,et al.  Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status. , 1998, The New England journal of medicine.

[44]  Jun Sun,et al.  Selenium inhibits Staphylococcus aureus-induced inflammation by suppressing the activation of the NF-κB and MAPK signalling pathways in RAW264.7 macrophages. , 2016, European journal of pharmacology.

[45]  J. Doroshow,et al.  Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents. , 1992, Blood.

[46]  B. Rapoport,et al.  Variable Effects of Dietary Selenium in Mice That Spontaneously Develop a Spectrum of Thyroid Autoantibodies , 2017, Endocrinology.

[47]  V. Potter,et al.  A New Toxicant Occurring Naturally in Certain Samples of Plant Foodstuffs , 1934 .

[48]  Y. Hirabayashi,et al.  Identification and characterization of human ethanolaminephosphotransferase1 Published, JLR Papers in Press, November 28, 2006. , 2007, Journal of Lipid Research.

[49]  A. Krol,et al.  Selenoprotein function and muscle disease. , 2009, Biochimica et biophysica acta.

[50]  A. Ostadrahimi,et al.  Effect of vitamin E and selenium supplementation on oxidative stress status in pulmonary tuberculosis patients , 2008, Respirology.

[51]  R. Schulte‐Hermann,et al.  Impact of glutathione peroxidase 4 on cell proliferation, angiogenesis and cytokine production in hepatocellular carcinoma , 2018, Oncotarget.

[52]  H. Ganther,et al.  In vitro and in vivo studies of methylseleninic acid: evidence that a monomethylated selenium metabolite is critical for cancer chemoprevention. , 2000, Cancer research.

[53]  K. Esser,et al.  Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth. , 2003, The Journal of nutrition.

[54]  Jennifer D. Wu,et al.  NKG2D Ligands in Tumor Immunity: Two Sides of a Coin , 2015, Front. Immunol..

[55]  V. Darras,et al.  Iodothyronine deiodinase structure and function: from ascidians to humans. , 2012, The Journal of endocrinology.

[56]  S. Novoselov,et al.  Mammalian Selenoprotein Thioredoxin-glutathione Reductase , 2005, Journal of Biological Chemistry.

[57]  L. Hooper,et al.  Methods of assessment of selenium status in humans: a systematic review. , 2009, The American journal of clinical nutrition.

[58]  L. Schomburg,et al.  Efficient selenium transfer from mother to offspring in selenoprotein-P-deficient mice enables dose-dependent rescue of phenotypes associated with selenium deficiency. , 2004, The Biochemical journal.

[59]  V. Gladyshev,et al.  Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein , 2014, PloS one.

[60]  T. Crawford,et al.  Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle , 2008, Proceedings of the National Academy of Sciences.

[61]  J. Kyle,et al.  An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. , 2004, The American journal of clinical nutrition.

[62]  G. Combs,et al.  Plasma Selenium Concentrations Are Sufficient and Associated with Protease Inhibitor Use in Treated HIV-Infected Adults. , 2015, The Journal of nutrition.

[63]  R. Hondal,et al.  Selenoprotein K Increases Efficiency of DHHC6 Catalyzed Protein Palmitoylation by Stabilizing the Acyl-DHHC6 Intermediate , 2017, Antioxidants.

[64]  Meng-yao Guo,et al.  Selenium Deficiency Facilitates Inflammation Through the Regulation of TLR4 and TLR4-Related Signaling Pathways in the Mice Uterus , 2015, Inflammation.

[65]  W. Willett,et al.  A prospective study of plasma selenium levels and prostate cancer risk. , 2004, Journal of the National Cancer Institute.

[66]  H. Satoh,et al.  Separation of selenium-containing proteins in human and mouse plasma using tandem high-performance liquid chromatography columns coupled with inductively coupled plasma-mass spectrometry. , 1999, Analytical biochemistry.

[67]  S. Yadav,et al.  Plasma selenium level in cancer patients. , 1994, Indian journal of cancer.

[68]  Sanjay Kumar,et al.  Selenium nanoparticles induce suppressed function of tumor associated macrophages and inhibit Dalton's lymphoma proliferation , 2017, Biochemistry and biophysics reports.

[69]  V. Gladyshev,et al.  MsrB1 and MICALs regulate actin assembly and macrophage function via reversible stereoselective methionine oxidation. , 2013, Molecular cell.

[70]  L. Allen,et al.  Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women. , 2015, The Journal of nutrition.

[71]  I. Kim,et al.  Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein. , 2014, Biochimica et biophysica acta.

[72]  L. Flohé,et al.  Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues. , 2003, The Biochemical journal.

[73]  G. Powis,et al.  The Absence of Mitochondrial Thioredoxin 2 Causes Massive Apoptosis, Exencephaly, and Early Embryonic Lethality in Homozygous Mice , 2003, Molecular and Cellular Biology.

[74]  V. Gladyshev,et al.  The Sep15 protein family: Roles in disulfide bond formation and quality control in the endoplasmic reticulum , 2007, IUBMB life.

[75]  Joep Lange,et al.  The spread, treatment, and prevention of HIV-1: evolution of a global pandemic. , 2008, The Journal of clinical investigation.

[76]  M. Taketo,et al.  Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene (Trsp). , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[77]  M. Conrad Transgenic mouse models for the vital selenoenzymes cytosolic thioredoxin reductase, mitochondrial thioredoxin reductase and glutathione peroxidase 4. , 2009, Biochimica et biophysica acta.

[78]  J. Urban,et al.  Selenium Status Alters the Immune Response and Expulsion of Adult Heligmosomoides bakeri Worms in Mice , 2013, Infection and Immunity.

[79]  L. Azzalis,et al.  Impact of Selenium Supplementation in Neutropenia and Immunoglobulin Production in Childhood Cancer Patients. , 2016, Journal of medicinal food.

[80]  Fukun W. Hoffmann,et al.  Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex , 2014, Proceedings of the National Academy of Sciences.

[81]  P. Hoffmann,et al.  The human selenoproteome: recent insights into functions and regulation , 2009, Cellular and Molecular Life Sciences.

[82]  M. Nazıroğlu,et al.  Selenium Reduces Oxidative Stress and Calcium Entry Through TRPV1 Channels in the Neutrophils of Patients with Polycystic Ovary Syndrome , 2014, Biological Trace Element Research.

[83]  S. Bera,et al.  Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention? , 2013, Mutagenesis.

[84]  L. Schomburg,et al.  Hierarchical regulation of selenoprotein expression and sex-specific effects of selenium. , 2009, Biochimica et biophysica acta.

[85]  R. Paulson,et al.  The Regulation of Pathways of Inflammation and Resolution in Immune Cells and Cancer Stem Cells by Selenium. , 2017, Advances in cancer research.

[86]  M. Beck Selenium and host defence towards viruses , 1999, Proceedings of the Nutrition Society.

[87]  T. Sudarsanam,et al.  Nutritional supplements for people being treated for active tuberculosis , 2016, The Cochrane database of systematic reviews.

[88]  Fukun W. Hoffmann,et al.  Selenoprotein K Knockout Mice Exhibit Deficient Calcium Flux in Immune Cells and Impaired Immune Responses , 2011, The Journal of Immunology.

[89]  P. Hoffmann,et al.  Selenoprotein K and protein palmitoylation. , 2015, Antioxidants & redox signaling.

[90]  R. Guigó,et al.  Characterization of Mammalian Selenoproteomes , 2003, Science.

[91]  R. Shivakoti,et al.  Prevalence and risk factors of micronutrient deficiencies pre- and post-antiretroviral therapy (ART) among a diverse multicountry cohort of HIV-infected adults. , 2016, Clinical nutrition.

[92]  P. Taylor,et al.  The effects of dietary selenium on the immune system in healthy men , 2001, Biological Trace Element Research.

[93]  A. Walch,et al.  Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis , 2017, Cell.

[94]  Xiong Guo,et al.  Chondrocyte apoptosis and expression of Bcl-2, Bax, Fas, and iNOS in articular cartilage in patients with Kashin-Beck disease. , 2006, The Journal of rheumatology.

[95]  D. Hedderley,et al.  Consumption of selenium-enriched broccoli increases cytokine production in human peripheral blood mononuclear cells stimulated ex vivo, a preliminary human intervention study. , 2014, Molecular nutrition & food research.

[96]  Fukun W. Hoffmann,et al.  Increasing dietary selenium elevates reducing capacity and ERK activation associated with accelerated progression of select mesothelioma tumors. , 2014, The American journal of pathology.

[97]  B. Seliger,et al.  Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid , 2017, Oncoimmunology.

[98]  N. Morse,et al.  A Review of Dietary Selenium Intake and Selenium Status in Europe and the Middle East , 2015, Nutrients.

[99]  K. Overvad,et al.  Selenium in human mammary carcinogenesis: a case-cohort study. , 1991, European Journal of Cancer.

[100]  R. Brigelius-Flohé,et al.  Gastrointestinal glutathione peroxidase , 1999, BioFactors.

[101]  J. Morrow,et al.  Liver and kidney necrosis in selenium-deficient rats depleted of glutathione. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[102]  Cheat Sheet Selenium , 2018, Reactions Weekly.

[103]  X. Lei,et al.  Metabolic regulation and function of glutathione peroxidase-1. , 2007, Annual review of nutrition.

[104]  A. Favier,et al.  Stimulation of glutathione peroxidase activity decreases HIV type 1 activation after oxidative stress. , 1994, AIDS research and human retroviruses.

[105]  F. Bloom,et al.  Nutrition Classics: Science, Volume 179, 1973, pages 588-591: Selenium: biochemical role as a component of glutathione peroxidase. , 1980, Nutrition reviews.

[106]  W. Willett,et al.  A prospective study of selenium status and breast cancer risk. , 1990, JAMA.

[107]  Caitlyn W. Barrett,et al.  Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut , 2017, Cellular and Molecular Life Sciences.

[108]  M. Berry,et al.  Nonsense-mediated decay factors are involved in the regulation of selenoprotein mRNA levels during selenium deficiency , 2014, RNA.

[109]  D. Goldowitz,et al.  Brainstem Axonal Degeneration in Mice with Deletion of Selenoprotein P , 2005, Toxicologic pathology.

[110]  M. Watarai,et al.  Contribution of methionine sulfoxide reductase B (MsrB) to Francisella tularensis infection in mice , 2017, FEMS microbiology letters.

[111]  V. Kataja,et al.  Toenail selenium and breast cancer—a case-control study in Finland , 2000, European Journal of Clinical Nutrition.

[112]  M. Faramarzi,et al.  The Immunostimulatory Effect of Biogenic Selenium Nanoparticles on the 4T1 Breast Cancer Model: an In Vivo Study , 2012, Biological Trace Element Research.

[113]  A. Akinboro,et al.  The impacts of first line highly active antiretroviral therapy on serum selenium, cd4 count and body mass index: a cross sectional and short prospective study , 2013, The Pan African medical journal.

[114]  C. Davis,et al.  Determinants of selenium status in healthy adults , 2011, Nutrition journal.

[115]  R. Norton,et al.  Selenoprotein K regulation of palmitoylation and calpain cleavage of ASAP2 is required for efficient FcγR‐mediated phagocytosis , 2017, Journal of leukocyte biology.

[116]  C. Hart,et al.  Are there functional consequences of a reduction in selenium intake in UK subjects? , 2004, Proceedings of the Nutrition Society.

[117]  K. Schwarz,et al.  Selenium as an integral part of Factor 3 against dietary necrotic liver degeneration. , 1957 .

[118]  J. Loscalzo,et al.  Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. , 2011, Antioxidants & redox signaling.

[119]  S. Novoselov,et al.  MsrB1 (Methionine-R-sulfoxide Reductase 1) Knock-out Mice , 2009, Journal of Biological Chemistry.

[120]  A. Floegel,et al.  Estimation of antioxidant intakes from diet and supplements in U.S. adults. , 2010, The Journal of nutrition.

[121]  G. Kryukov,et al.  Selenoprotein H Is a Nucleolar Thioredoxin-like Protein with a Unique Expression Pattern* , 2007, Journal of Biological Chemistry.

[122]  F. Muntoni,et al.  Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome , 2001, Nature Genetics.

[123]  B. Turnbull,et al.  Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[124]  R. Geisberger,et al.  B- and T-cell-specific inactivation of thioredoxin reductase 2 does not impair lymphocyte development and maintenance , 2007, Biological chemistry.

[125]  G. Stotzky,et al.  Supplementation with selenium augments the functions of natural killer and lymphokine-activated killer cells , 1996, Biological Trace Element Research.

[126]  G. Stotzky,et al.  Supplementation with Selenium Restores Age-Related Decline in Immune Cell Function , 1995, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[127]  Hung-Ming Wang,et al.  Reduction of Splenic Immunosuppressive Cells and Enhancement of Anti-Tumor Immunity by Synergy of Fish Oil and Selenium Yeast , 2013, PloS one.

[128]  M. Aribi,et al.  Macrophage Bactericidal Activities against Staphylococcus aureus Are Enhanced In Vivo by Selenium Supplementation in a Dose-Dependent Manner , 2015, PloS one.

[129]  A. Böck,et al.  The many levels of control on bacterial selenoprotein synthesis. , 2009, Biochimica et biophysica acta.

[130]  G. Combs Biomarkers of Selenium Status , 2015, Nutrients.

[131]  F. Muntoni,et al.  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. , 2002, American journal of human genetics.

[132]  Kristin Varsi,et al.  Impact of Maternal Selenium Status on Infant Outcome during the First 6 Months of Life , 2017, Nutrients.

[133]  W. Fawzi,et al.  Role of selenium in HIV infection. , 2010, Nutrition reviews.

[134]  S. Elledge,et al.  C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases. , 2018, Molecular cell.

[135]  Xiong Guo,et al.  [Expression of Caspase-8 and Bcl-2 in the cartilage loose bodies in patients with Kashin-Beck disease]. , 2011, Nan fang yi ke da xue xue bao = Journal of Southern Medical University.

[136]  M. De la Fuente,et al.  Improvement of leukocyte functions in young prematurely aging mice after a 5-week ingestion of a diet supplemented with biscuits enriched in antioxidants. , 2005, Antioxidants & redox signaling.

[137]  C. Anderson,et al.  Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice , 2015, Nutrients.

[138]  V. Gladyshev,et al.  Selenoproteins Mediate T Cell Immunity through an Antioxidant Mechanism* , 2008, Journal of Biological Chemistry.

[139]  R. Norton,et al.  Selenoprotein K is required for palmitoylation of CD36 in macrophages: implications in foam cell formation and atherogenesis , 2013, Journal of leukocyte biology.

[140]  Jason G. Belter,et al.  The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. , 2003, Free radical biology & medicine.

[141]  V. Gladyshev,et al.  International Immunonutrition Workshop Session 2 : Micronutrients and the immune system Role of selenium-containing proteins in T-cell and macrophage function , 2010 .

[142]  J. F. Atkins,et al.  Deletion of Selenoprotein P Alters Distribution of Selenium in the Mouse* , 2003, The Journal of Biological Chemistry.

[143]  N. Radhakrishnan,et al.  Antioxidant Levels at Diagnosis in Childhood Acute Lymphoblastic Leukemia , 2013, The Indian Journal of Pediatrics.

[144]  N. Rollins,et al.  Micronutrient supplementation for children with HIV infection. , 2013, The Cochrane database of systematic reviews.

[145]  J. Hesketh,et al.  Differential regulation of expression of cytosolic and mitochondrial thioredoxin reductase in rat liver and kidney. , 2007, Archives of biochemistry and biophysics.

[146]  C. Guo,et al.  Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C. , 2005, World journal of gastroenterology.

[147]  N. Nader,et al.  The Effect of Intravenous Selenium on Oxidative Stress in Critically Ill Patients with Acute Respiratory Distress Syndrome , 2018, Immunological investigations.

[148]  P. Guicheney,et al.  Selenoprotein N in skeletal muscle: from diseases to function , 2012, Journal of Molecular Medicine.

[149]  E. Adejuyigbe,et al.  Serum Micronutrient Status of Haart-Naïve, HIV Infected Children in South Western Nigeria: A Case Controlled Study , 2014, AIDS research and treatment.

[150]  R. Brigelius-Flohé,et al.  Revised reference values for selenium intake. , 2015, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[151]  V. Gladyshev,et al.  Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis , 2006, The Biochemical journal.

[152]  R. Burk,et al.  Neurological dysfunction occurs in mice with targeted deletion of the selenoprotein P gene. , 2004, The Journal of nutrition.

[153]  D. Behne,et al.  Evidence for specific selenium target tissues and new biologically important selenoproteins. , 1988, Biochimica et biophysica acta.

[154]  Abdallah Hamieh,et al.  Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease , 2016, Antioxidants & redox signaling.

[155]  D. Cucinotta,et al.  Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y. , 2000, The American journal of clinical nutrition.

[156]  M. Berry,et al.  Deletion of Selenoprotein M Leads to Obesity without Cognitive Deficits* , 2013, The Journal of Biological Chemistry.

[157]  R. Shivakoti,et al.  Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial. , 2019, Clinical nutrition.

[158]  C. Hiley,et al.  Methylseleninic acid inhibits HDAC activity in diffuse large B-cell lymphoma cell lines , 2011, Cancer Chemotherapy and Pharmacology.

[159]  L. Kiemeney,et al.  A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate , 2017, Oncotarget.

[160]  Xiong Guo,et al.  [Comparison of apoptosis of articular chondrocytes in the pathogenesis of Kashin-beck disease and primary osteoarthritis]. , 2006, Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae.

[161]  Gerhard K. H. Przemeck,et al.  Cytoplasmic Thioredoxin Reductase Is Essential for Embryogenesis but Dispensable for Cardiac Development , 2005, Molecular and Cellular Biology.

[162]  J. Finley Bioavailability of selenium from foods. , 2006, Nutrition reviews.

[163]  R. Schulte‐Hermann,et al.  Antagonistic effects of selenium and lipid peroxides on growth control in early hepatocellular carcinoma , 2012, Hepatology.

[164]  M. Rayman Selenium and human health , 2012, The Lancet.

[165]  G. Bornkamm,et al.  Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals , 2007, Biological chemistry.

[166]  S. Cockell,et al.  Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies , 2016, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[167]  K. Ge,et al.  Keshan disease-an endemic cardiomyopathy in China , 2004, Virchows Archiv A.

[168]  Shenika V. Poindexter,et al.  Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage. , 2015, The Journal of clinical investigation.

[169]  K. W. Franke A new toxicant occurring naturally in certain samples of plant foodstuffs. 1. Results obtained in preliminary feeding trials. , 1934 .

[170]  C. Nicoletti,et al.  Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults , 2017, Clinical nutrition.

[171]  T. Decsi,et al.  Methods of assessment of zinc status in humans: a systematic review. , 2009, The American journal of clinical nutrition.

[172]  L. Schomburg,et al.  Selenium status in neonates with connatal infection , 2016, British Journal of Nutrition.

[173]  A. Wendel,et al.  The Effect of Selenium on Immune Functions of J774.1 Cells , 2003, Clinical chemistry and laboratory medicine.

[174]  Arturo Hernandez,et al.  Thyroid hormone deiodinases: physiology and clinical disorders. , 2003, Current opinion in pediatrics.

[175]  M. Puertollano,et al.  Dietary antioxidants: immunity and host defense. , 2011, Current topics in medicinal chemistry.

[176]  L. Hegedüs,et al.  Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis. , 2016, Thyroid : official journal of the American Thyroid Association.