Advertisement

Biological Trace Element Research

, Volume 188, Issue 1, pp 189–195 | Cite as

The Thioredoxin-Like Family of Selenoproteins: Implications in Aging and Age-Related Degeneration

  • Li Zhang
  • Jian-Hong Zhu
  • Xiong Zhang
  • Wen-Hsing ChengEmail author
Article
  • 97 Downloads

Abstract

The thioredoxin-like (Rdx) family proteins contain four selenoproteins (selenoprotein H, SELENOH; selenoprotein T, SELENOT; selenoprotein V, SELENOV; selenoprotein W, SELENOW) and a nonselenoprotein Rdx12. They share a CxxU or a CxxC (C, cysteine; x, any amino acid; U, selenocysteine) motif and a stretch of eGxFEI(V) sequence. From the evolutionary perspective, SELENOW and SELENOV are clustered together and SELENOH and SELENOT are in another branch. Selenoproteins in the Rdx family exhibit tissue- and organelle-specific distribution and are differentially influenced in response to selenium deficiency. While SELENOH is nucleus-exclusive, SELENOT resides mainly in endoplasmic reticulum and SELENOW in cytosol. SELENOV is expressed essentially only in the testes with unknown cellular localization. SELENOH and SELENOW are more sensitive than SELENOT and SELENOV to selenium deficiency. While physiological functions of the Rdx family of selenoproteins are not fully understand, results from animal models demonstrated that (1) brain-specific SELENOT knockout mice are susceptible to 1-methyl-4-phenylpyridinium-induced Parkinson’s disease in association with redox imbalance and (2) adult zebrafishes with heterozygous SELENOH knockout are prone to dimethylbenzanthracene-induced tumorigenesis together with increased DNA damage and oxidative stress. Further animal and human studies are needed to fully understand physiological roles of the Rdx family of selenoproteins in redox regulation, genome maintenance, aging, and age-related degeneration.

Keywords

Selenium Selenoprotein H Selenoprotein T Selenoprotein W Selenoprotein V 

Notes

Funding information

This study is financially supported in part by the National Institute of Food and Agriculture (Multistate NE1439, accession no. 1008124, project no. MIS-384050), National Natural Science Foundation of China (81771510 to X Zhang), and Wenzhou Municipal Science and Technology Bureau (C20170003 to JH Zhu).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Lobanov AV, Hatfield DL, Gladyshev VN (2008) Selenoproteinless animals: selenophosphate synthetase SPS1 functions in a pathway unrelated to selenocysteine biosynthesis. Protein Sci 17:176–182CrossRefGoogle Scholar
  2. 2.
    Labunskyy VM, Hatfield DL, Gladyshev VN (2014) Selenoproteins: molecular pathways and physiological roles. Physiol Rev 94:739–777CrossRefGoogle Scholar
  3. 3.
    Zhang Y, Romero H, Salinas G, Gladyshev VN (2006) Dynamic evolution of selenocysteine utilization in bacteria: a balance between selenoprotein loss and evolution of selenocysteine from redox active cysteine residues. Genome Biol 7:R94CrossRefGoogle Scholar
  4. 4.
    Zhang X, Zhang L, Zhu JH, Cheng WH (2016) Nuclear selenoproteins and genome maintenance. IUBMB Life 68:5–12CrossRefGoogle Scholar
  5. 5.
    Zhang L, Zeng H, Cheng WH (2018) Beneficial and paradoxical roles of selenium at nutritional levels of intake in healthspan and longevity. Free Radic Biol Med doi.  https://doi.org/10.1016/j.freeradbiomed.2018.05.067
  6. 6.
    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 46:6871–6882CrossRefGoogle Scholar
  7. 7.
    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 281:3536–3543CrossRefGoogle Scholar
  8. 8.
    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 276:15330–15336CrossRefGoogle Scholar
  9. 9.
    Mariotti M, Ridge PG, Zhang Y, Lobanov AV, Pringle TH, Guigo R, Hatfield DL, Gladyshev VN (2012) Composition and evolution of the vertebrate and mammalian selenoproteomes. PLoS One 7:e33066CrossRefGoogle Scholar
  10. 10.
    Whanger PD (2009) Selenoprotein expression and function-selenoprotein W. Biochim Biophys Acta 1790:1448–1452CrossRefGoogle Scholar
  11. 11.
    Cao L, Zhang L, Zeng H, Wu RT, Wu TL, Cheng WH (2017) Analyses of Selenotranscriptomes and selenium concentrations in response to dietary selenium deficiency and age reveal common and distinct patterns by tissue and sex in telomere-dysfunctional mice. J Nutr 147:1858–1866CrossRefGoogle Scholar
  12. 12.
    Tanguy Y, Falluel-Morel A, Arthaud S, Boukhzar L, Manecka DL, Chagraoui A, Prevost G, Elias S, Dorval-Coiffec I, Lesage J, Vieau D, Lihrmann I, Jegou B, Anouar Y (2011) The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes. Endocrinology 152:4322–4335CrossRefGoogle Scholar
  13. 13.
    Hamieh A, Cartier D, Abid H, Calas A, Burel C, Bucharles C, Jehan C, Grumolato L, Landry M, Lerouge P, Anouar Y, Lihrmann I (2017) Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion. EMBO Rep 18:1935–1946CrossRefGoogle Scholar
  14. 14.
    Prevost G, Arabo A, Jian L, Quelennec E, Cartier D, Hassan S, Falluel-Morel A, Tanguy Y, Gargani S, Lihrmann I, Kerr-Conte J, Lefebvre H, Pattou F, Anouar Y (2013) The PACAP-regulated gene selenoprotein T is abundantly expressed in mouse and human beta-cells and its targeted inactivation impairs glucose tolerance. Endocrinology 154:3796–3806CrossRefGoogle Scholar
  15. 15.
    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 282:11960–11968CrossRefGoogle Scholar
  16. 16.
    Sunde RA, Raines AM (2011) Selenium regulation of the selenoprotein and nonselenoprotein transcriptomes in rodents. Adv Nutr 2:138–150CrossRefGoogle Scholar
  17. 17.
    Chen XD, Zhao ZP, Zhou JC, Lei XG (2018) Evolution, regulation, and function of porcine selenogenome. Free Radic Biol Med doi.  https://doi.org/10.1016/j.freeradbiomed.2018.04.560
  18. 18.
    Boukhzar L, Hamieh A, Cartier D, Tanguy Y, Alsharif I, Castex M, Arabo A, El Hajji S, Bonnet JJ, Errami M, Falluel-Morel A, Chagraoui A, Lihrmann I, Anouar Y (2016) Selenoprotein T exerts an essential oxidoreductase activity that protects dopaminergic neurons in mouse models of Parkinson’s disease. Antioxid Redox Signal 24:557–574Google Scholar
  19. 19.
    Zhao H, Li K, Tang JY, Zhou JC, Wang KN, Xia XJ, Lei XG (2015) Expression of selenoprotein genes is affected by obesity of pigs fed a high-fat diet. J Nutr 145:1394–1401CrossRefGoogle Scholar
  20. 20.
    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 22:1756–1768CrossRefGoogle Scholar
  21. 21.
    Sung YH, Baek IJ, Kim DH, Jeon J, Lee J, Lee K, Jeong D, Kim JS, Lee HW (2013) Knockout mice created by TALEN-mediated gene targeting. Nat Biotechnol 31:23–24CrossRefGoogle Scholar
  22. 22.
    Castex MT, Arabo A, Benard M, Roy V, Le Joncour V, Prevost G, Bonnet JJ, Anouar Y, Falluel-Morel A (2016) Selenoprotein T deficiency leads to neurodevelopmental abnormalities and hyperactive behavior in mice. Mol Neurobiol 53:5818–5832Google Scholar
  23. 23.
    Wu RT, Cao L, Chen BP, Cheng WH (2014) Selenoprotein H suppresses cellular senescence through genome maintenance and redox regulation. J Biol Chem 289:34378–34388CrossRefGoogle Scholar
  24. 24.
    Mendelev N, Mehta SL, Witherspoon S, He Q, Sexton JZ, Li PA (2011) Upregulation of human selenoprotein H in murine hippocampal neuronal cells promotes mitochondrial biogenesis and functional performance. Mitochondrion 11:76–82CrossRefGoogle Scholar
  25. 25.
    Ben Jilani KE, Panee J, He Q, Berry MJ, Li PA (2007) Overexpression of selenoprotein H reduces Ht22 neuronal cell death after UVB irradiation by preventing superoxide formation. Int J Biol Sci 3:198–204CrossRefGoogle Scholar
  26. 26.
    Jeon YH, Ko KY, Lee JH, Park KJ, Jang JK, Kim IY (2016) Identification of a redox-modulatory interaction between selenoprotein W and 14-3-3 protein. Biochim Biophys Acta 1863:10–18CrossRefGoogle Scholar
  27. 27.
    Cornell B, Toyo-Oka K (2017) 14-3-3 proteins in brain development: neurogenesis, neuronal migration and neuromorphogenesis. Front Mol Neurosci 10:318CrossRefGoogle Scholar
  28. 28.
    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 282:23759–23765CrossRefGoogle Scholar
  29. 29.
    Stoytcheva ZR, Vladimirov V, Douet V, Stoychev I, Berry MJ (2010) Metal transcription factor-1 regulation via MREs in the transcribed regions of selenoprotein H and other metal-responsive genes. Biochim Biophys Acta 1800:416–424CrossRefGoogle Scholar
  30. 30.
    Cox AG, Tsomides A, Kim AJ, Saunders D, Hwang KL, Evason KJ, Heidel J, Brown KK, Yuan M, Lien EC, Lee BC, Nissim S, Dickinson B, Chhangawala S, Chang CJ, Asara JM, Houvras Y, Gladyshev VN, Goessling W (2016) Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis. Proc Natl Acad Sci U S A 113:E5562–E5571CrossRefGoogle Scholar
  31. 31.
    Bertz M, Kuhn K, Koeberle SC, Muller MF, Hoelzer D, Thies K, Deubel S, Thierbach R, Kipp AP (2018) Selenoprotein H controls cell cycle progression and proliferation of human colorectal cancer cells. Free Radic Biol Med doi.  https://doi.org/10.1016/j.freeradbiomed.2018.01.010
  32. 32.
    Sengupta A, Carlson BA, Labunskyy VM, Gladyshev VN, Hatfield DL (2009) Selenoprotein T deficiency alters cell adhesion and elevates selenoprotein W expression in murine fibroblast cells. Biochem Cell Biol 87:953–961CrossRefGoogle Scholar
  33. 33.
    Behne D, Hofer T, von Berswordt-Wallrabe R, Elger W (1982) Selenium in the testis of the rat: studies on its regulation and its importance for the organism. J Nutr 112:1682–1687Google Scholar
  34. 34.
    Pitts MW, Kremer PM, Hashimoto AC, Torres DJ, Byrns CN, Williams CS, Berry MJ (2015) Competition between the brain and testes under selenium-compromised conditions: insight into sex differences in selenium metabolism and risk of neurodevelopmental disease. J Neurosci 35:15326–15338CrossRefGoogle Scholar
  35. 35.
    Tamura K, Ne M (1993) Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol 10:512–526Google Scholar
  36. 36.
    Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35:1547–1549CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Li Zhang
    • 1
    • 2
  • Jian-Hong Zhu
    • 3
    • 4
  • Xiong Zhang
    • 4
  • Wen-Hsing Cheng
    • 1
    Email author
  1. 1.Department of Food Science, Nutrition and Health PromotionMississippi State UniversityMississippi StateUSA
  2. 2.Department of Poultry ScienceMississippi State UniversityMississippi StateUSA
  3. 3.Department of Preventive Medicine, School of Public HealthWenzhou Medical UniversityWenzhouChina
  4. 4.Department of Geriatrics and Neurology, The Second Affiliated Hospital and Yuying Children’s HospitalWenzhou Medical UniversityWenzhouChina

Personalised recommendations