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Selenium involvement in mitochondrial function in thyroid disorders

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Abstract

Selenium (Se), an important oligoelement, is a component of the antioxidant system. Over the last decade, it has been ever more frequently discussed in the context of thyroid disorders. Graves’ disease and Hashimoto’s thyroiditis, differentiated thyroid cancer, and even endemic goiter may have common triggers that are activated by excess reactive oxygen species (ROS), which are involved in various stages of the pathogenesis of thyroid disorders. Most oxidative events occur in mitochondria, organelles that contain enzymes with Se as a cofactor. Mitochondria are responsible for the production of ATP in the cell and are also a major site of ROS production. Thyroid hormone status (the thyroid being the organ with the highest concentration of Se in the body) has a profound impact on mitochondria biogenesis. In this review, we focus on the role of Se in mitochondrial function in thyroid disorders with impaired oxidative stress, since both thyroid hormone synthesis and thyroid dysfunction involve ROS. The role of Se deficiency or its excess in relation to mitochondrial dysfunction in the context of thyroid disorders is therefore of interest.

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References

  1. Rizzo AM, Berselli P, Zava S, Montorfano G, Negroni M, Corsetto P, Berra B (2010) Endogenous antioxidants and radical scavengers. Adv Exp Med Biol 698:52–67

    CAS  PubMed  Google Scholar 

  2. Di MS, Reed TT, Venditti P, Victor VM (2016) Role of ROS and RNS sources in physiological and pathological conditions. Oxidative Med Cell Longev 2016:1245049

    Google Scholar 

  3. Duntas LH, Benvenga S (2015) Selenium: an element for life. Endocrine 48:756–775

    CAS  PubMed  Google Scholar 

  4. Wallenberg M, Misra S, Bjornstedt M (2014) Selenium cytotoxicity in cancer. Basic Clin Pharmacol Toxicol 114:377–386

    CAS  PubMed  Google Scholar 

  5. Kurokawa S, Takehashi M, Tanaka H, Mihara H, Kurihara T, Tanaka S, Hill K, Burk R, Esaki N (2011) Mammalian selenocysteine lyase is involved in selenoprotein biosynthesis. J Nutr Sci Vitaminol (Tokyo) 57:298–305

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  7. Labunskyy VM, Hatfield DL, Gladyshev VN (2014) Selenoproteins: molecular pathways and physiological roles. Physiol Rev 94:739–777

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Schomburg L (2011) Selenium, selenoproteins and the thyroid gland: interactions in health and disease. Nat Rev Endocrinol 8:160–171

    PubMed  Google Scholar 

  9. Valea A, Georgescu CE (2018) Selenoproteins in human body: focus on thyroid pathophysiology. Hormones (Athens ) 17:183–196

    Google Scholar 

  10. Biesalski HK (2002) Meat and cancer: meat as a component of a healthy diet. Eur J Clin Nutr 56(Suppl 1):S2–S11

    PubMed  Google Scholar 

  11. Faria CC, Peixoto MS, Carvalho DP, Fortunato RS (2019) The emerging role of estrogens in thyroid redox homeostasis and carcinogenesis. Oxidative Med Cell Longev 2019:2514312

    Google Scholar 

  12. Schweizer U, Chiu J, Kohrle J (2008) Peroxides and peroxide-degrading enzymes in the thyroid. Antioxid Redox Signal 10:1577–1592

    CAS  PubMed  Google Scholar 

  13. Szanto I, Pusztaszeri M, Mavromati M (2019) H2O2 metabolism in normal thyroid cells and in thyroid tumorigenesis: focus on NADPH oxidases. Antioxidants (Basel) 8

  14. Lushchak VI (2014) Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact 224:164–175

    CAS  PubMed  Google Scholar 

  15. Ghaddhab C, Kyrilli A, Driessens N, Van Den Eeckhaute E, Hancisse O, De Deken X, Dumont JE, Detours V, Miot F, Corvilain B (2019) Factors contributing to the resistance of the thyrocyte to hydrogen peroxide. Mol Cell Endocrinol 481:62–70

    CAS  PubMed  Google Scholar 

  16. Maouche N, Meskine D, Alamir B, Koceir EA (2015) Trace elements profile is associated with insulin resistance syndrome and oxidative damage in thyroid disorders: manganese and selenium interest in Algerian participants with dysthyroidism. J Trace Elem Med Biol 32:112–121

    CAS  PubMed  Google Scholar 

  17. Ylikallio E, Suomalainen A (2012) Mechanisms of mitochondrial diseases. Ann Med 44:41–59

    CAS  PubMed  Google Scholar 

  18. Di DG, Hirshberg J, Lyle D, Freij JB, Caturegli P (2016) Reactive oxygen species in organ-specific autoimmunity. Auto Immun Highlights 7:11

    Google Scholar 

  19. Wesselink E, Koekkoek WAC, Grefte S, Witkamp RF, van Zanten ARH (2018) Feeding mitochondria: potential role of nutritional components to improve critical illness convalescence. Clin Nutr

  20. Harrois A, Huet O, Duranteau J (2009) Alterations of mitochondrial function in sepsis and critical illness. Curr Opin Anaesthesiol 22:143–149

    PubMed  Google Scholar 

  21. Selivanov VA, Votyakova TV, Pivtoraiko VN, Zeak J, Sukhomlin T, Trucco M, Roca J, Cascante M (2011) Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLoS Comput Biol 7:e1001115

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Liemburg-Apers DC, Willems PH, Koopman WJ, Grefte S (2015) Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Arch Toxicol 89:1209–1226

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Galley HF (2011) Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth 107:57–64

    CAS  PubMed  Google Scholar 

  24. Cline SD (2012) Mitochondrial DNA damage and its consequences for mitochondrial gene expression. Biochim Biophys Acta 1819:979–991

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Forini F, Nicolini G, Kusmic C, Iervasi G (2019) Protective effects of euthyroidism restoration on mitochondria function and quality control in cardiac pathophysiology. Int J Mol Sci 20

    CAS  PubMed Central  Google Scholar 

  26. de Castro AL, Tavares AV, Fernandes RO, Campos C, Conzatti A, Siqueira R, Fernandes TR, Schenkel PC, Sartorio CL, Llesuy S, Bello-Klein A, da Rosa Araujo AS (2015) T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats. Mol Cell Biochem 408:235–243

    PubMed  Google Scholar 

  27. Forini F, Nicolini G, Kusmic C, D'Aurizio R, Rizzo M, Baumgart M, Groth M, Doccini S, Iervasi G, Pitto L (2018) Integrative analysis of differentially expressed genes and miRNAs predicts complex T3-mediated protective circuits in a rat model of cardiac ischemia reperfusion. Sci Rep 8:13870

    PubMed  PubMed Central  Google Scholar 

  28. Xu M, Wang Y, Ayub A, Ashraf M (2001) Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential. Am J Physiol Heart Circ Physiol 281:H1295–H1303

    CAS  PubMed  Google Scholar 

  29. Chi HC, Tsai CY, Tsai MM, Yeh CT, Lin KH (2019) Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases. J Biomed Sci 26:24

    PubMed  PubMed Central  Google Scholar 

  30. Yau WW, Singh BK, Lesmana R, Zhou J, Sinha RA, Wong KA, Wu Y, Bay BH, Sugii S, Sun L, Yen PM (2019) Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy. Autophagy 15:131–150

    CAS  PubMed  Google Scholar 

  31. Mehta SL, Kumari S, Mendelev N, Li PA (2012) Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. BMC Neurosci 13:79

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Cheng SY, Leonard JL, Davis PJ (2010) Molecular aspects of thyroid hormone actions. Endocr Rev 31:139–170

    CAS  PubMed  PubMed Central  Google Scholar 

  33. de Vries EM, Fliers E, Boelen A (2015) The molecular basis of the non-thyroidal illness syndrome. J Endocrinol 225:R67–R81

    PubMed  Google Scholar 

  34. Berger MM, Lemarchand-Beraud T, Cavadini C, Chiolero R (1996) Relations between the selenium status and the low T3 syndrome after major trauma. Intensive Care Med 22:575–581

    CAS  PubMed  Google Scholar 

  35. Schomburg L, Riese C, Michaelis M, Griebert E, Klein MO, Sapin R, Schweizer U, Kohrle J (2006) Synthesis and metabolism of thyroid hormones is preferentially maintained in selenium-deficient transgenic mice. Endocrinology 147:1306–1313

    CAS  PubMed  Google Scholar 

  36. Angstwurm MW, Schopohl J, Gaertner R (2004) Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients. Eur J Endocrinol 151:47–54

    CAS  PubMed  Google Scholar 

  37. Manzanares W, Lemieux M, Elke G, Langlois PL, Bloos F, Heyland DK (2016) High-dose intravenous selenium does not improve clinical outcomes in the critically ill: a systematic review and meta-analysis. Crit Care 20:356

    PubMed  PubMed Central  Google Scholar 

  38. Olivieri O, Girelli D, Stanzial AM, Rossi L, Bassi A, Corrocher R (1996) Selenium, zinc, and thyroid hormones in healthy subjects: low T3/T4 ratio in the elderly is related to impaired selenium status. Biol Trace Elem Res 51:31–41

    CAS  PubMed  Google Scholar 

  39. McLachlan SM, Aliesky H, Banuelos B, Hee SSQ, Rapoport B (2017) Variable effects of dietary selenium in mice that spontaneously develop a spectrum of thyroid autoantibodies. Endocrinology 158:3754–3764

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Brcic L, Baric A, Gracan S, Torlak V, Brekalo M, Skrabic V, Zemunik T, Barbalic M, Punda A, Boraska PV (2019) Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis. Sci Rep 9:5360

    PubMed  PubMed Central  Google Scholar 

  41. Duthoit C, Estienne V, Giraud A, Durand-Gorde JM, Rasmussen AK, Feldt-Rasmussen U, Carayon P, Ruf J (2001) Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity? Biochem J 360:557–562

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Niethammer P, Grabher C, Look AT, Mitchison TJ (2009) A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 459:996–999

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Duntas LH (2015) The role of iodine and selenium in autoimmune thyroiditis. Horm Metab Res 47:721–726

    CAS  PubMed  Google Scholar 

  44. Ates I, Yilmaz FM, Altay M, Yilmaz N, Berker D, Guler S (2015) The relationship between oxidative stress and autoimmunity in Hashimoto’s thyroiditis. Eur Fed Endocr Soc 173(6):791–799. https://doi.org/10.1530/EJE-15-0617

    Article  CAS  Google Scholar 

  45. Baser H, Can U, Baser S, Yerlikaya FH, Aslan U, Hidayetoglu BT (2015) Assessment of oxidative status and its association with thyroid autoantibodies in patients with euthyroid autoimmune thyroiditis. Endocrine 48:916–923

    CAS  PubMed  Google Scholar 

  46. Ruggeri RM, Vicchio TM, Cristani M, Certo R, Caccamo D, Alibrandi A, Giovinazzo S, Saija A, Campenni A, Trimarchi F, Gangemi S (2016) Oxidative stress and advanced glycation end products in Hashimoto’s thyroiditis. Thyroid 26:504–511

    CAS  PubMed  Google Scholar 

  47. Pritchard J, Han R, Horst N, Cruikshank WW, Smith TJ (2003) Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves’ disease is mediated through the insulin-like growth factor I receptor pathway. J Immunol 170:6348–6354

    CAS  PubMed  Google Scholar 

  48. Marcocci C, Bartalena L (2013) Role of oxidative stress and selenium in Graves’ hyperthyroidism and orbitopathy. J Endocrinol Investig 36:15–20

    CAS  Google Scholar 

  49. Duntas LH (2012) The evolving role of selenium in the treatment of Graves’ disease and ophthalmopathy. J Thyroid Res 2012:736161

    PubMed  PubMed Central  Google Scholar 

  50. Teixeira RB, Fernandes-Piedras TRG, Bello-Klein A, Carraro CC, Araujo ASDR (2019) An early stage in T4-induced hyperthyroidism is related to systemic oxidative stress but does not influence the pentose cycle in erythrocytes and systemic inflammatory status. Arch Endocrinol Metab

  51. Komosinska-Vassev K, Olczyk K, Kucharz EJ, Marcisz C, Winsz-Szczotka K, Kotulska A (2000) Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves’ disease during therapy. Clin Chim Acta 300:107–117

    CAS  PubMed  Google Scholar 

  52. Kocak M, Akarsu E, Korkmaz H, Taysi S (2019) The effect of antithyroid drugs on osteopontin and oxidative stress in Graves’ disease. Acta Endocrinol (Buchar ) 15:221–224

    CAS  Google Scholar 

  53. Ademoglu E, Ozbey N, Erbil Y, Tanrikulu S, Barbaros U, Yanik BT, Bozbora A, Ozarmagan S (2006) Determination of oxidative stress in thyroid tissue and plasma of patients with Graves’ disease. Eur J Intern Med 17:545–550

    CAS  PubMed  Google Scholar 

  54. Kihara M, Kontani K, Yamauchi A, Miyauchi A, Nakamura H, Yodoi J, Yokomise H (2005) Expression of thioredoxin in patients with Graves’ disease. Int J Mol Med 15:795–799

    CAS  PubMed  Google Scholar 

  55. Choi W, Li Y, Ji YS, Yoon KC (2018) Oxidative stress markers in tears of patients with Graves’ orbitopathy and their correlation with clinical activity score. BMC Ophthalmol 18:303

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Ursu HI, Badiu C, Gheorghiu ML (2012) Selenium, mild Graves ophtalmopathy and current smoking status. Acta Endo (Buc) 8:467–470

    CAS  Google Scholar 

  57. Zhang F, Yu W, Hargrove JL, Greenspan P, Dean RG, Taylor EW, Hartle DK (2002) Inhibition of TNF-alpha induced ICAM-1, VCAM-1 and E-selectin expression by selenium. Atherosclerosis 161:381–386

    CAS  PubMed  Google Scholar 

  58. Li YB, Han JY, Jiang W, Wang J (2011) Selenium inhibits high glucose-induced cyclooxygenase-2 and P-selectin expression in vascular endothelial cells. Mol Biol Rep 38:2301–2306

    CAS  PubMed  Google Scholar 

  59. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    CAS  PubMed  Google Scholar 

  60. Bhattacharjee A, Basu A, Sen T, Biswas J, Battacharya S (2017) Nano-Se as a novel candidate in the management of oxidative stress related disorders and cancer. Nucleus:137–145

  61. Kong L, Yuan Q, Zhu H, Li Y, Guo Q, Wang Q, Bi X, Gao X (2011) The suppression of prostate LNCaP cancer cells growth by selenium nanoparticles through Akt/Mdm2/AR controlled apoptosis. Biomaterials 32:6515–6522

    CAS  PubMed  Google Scholar 

  62. Lee KH, Jeong D (2012) Bimodal actions of selenium essential for antioxidant and toxic pro-oxidant activities: the selenium paradox (review). Mol Med Rep 5:299–304

    CAS  PubMed  Google Scholar 

  63. Cao TM, Hua FY, Xu CM, Han BS, Dong H, Zuo L, Wang X, Yang Y, Pan HZ, Zhang ZN (2006) Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells. Ann Hematol 85:434–442

    CAS  PubMed  Google Scholar 

  64. Collery P (2018) Strategies for the development of selenium-based anticancer drugs. J Trace Elem Med Biol 50:498–507

    CAS  PubMed  Google Scholar 

  65. Negro R, Hegedus L, Attanasio R, Papini E, Winther KH (2019) A 2018 European thyroid association survey on the use of selenium supplementation in Graves’ hyperthyroidism and Graves’ orbitopathy. Eur Thyroid J 8:7–15

    PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Prof. Leonidas Duntas for his constructive criticism and scientific guidance in the elaboration of this manuscript.

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Correspondence to Corin Badiu.

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Gheorghiu, M.L., Badiu, C. Selenium involvement in mitochondrial function in thyroid disorders. Hormones 19, 25–30 (2020). https://doi.org/10.1007/s42000-020-00173-2

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