Selenium pp 471-479 | Cite as

Selenoproteins in Parasites

  • Gustavo Salinas
  • Mariana Bonilla
  • Lucía Otero
  • Alexey V. Lobanov
  • Vadim N. Gladyshev
Chapter

Abstract

Parasites are organisms that live, at least part of their lifecycle, inside another organism (the host), which they exploit for their own benefit. Parasite infections are highly prevalent in vast tropical regions and cause a wide variety of human-neglected diseases. Significant advances have been made in the identification and characterization of selenoproteins of both major groups of human parasites: protozoan (unicellular) and helminth (worm) parasites. Some selenoprotein mRNAs had a highly efficient noncanonical form of eukaryotic SECIS element. A major finding has been the identification of the selenoprotein thioredoxin glutathione reductase (TGR) as the single redox wire for electron transfer to both thioredoxin and glutathione pathways in flatworm parasites (phylum Platyhelminthes). Further studies validated TGR as a novel drug target and identified drug leads that show great promise for treatment of flatworm infections by disrupting parasite redox homeostasis. Interestingly, lineage-specific selenoprotein families are present in medically important protozoan parasites, but are absent in their hosts.

Keywords

Glutathione Selenium Disulfide NADPH Methionine 

Notes

Acknowledgements

This work was supported by PDT 63-105 grant from the Uruguayan Research Council and FIRCA-NIH Grant TW008588 to GS, NIH grant GM065204 to VNG, and PEDECIBA/ANII and CSIC postgraduate fellowships to MB.

References

  1. 1.
    Hotez PJ, Brindley PJ, Bethony JM et al (2008) J Clin Invest 118:1311PubMedCrossRefGoogle Scholar
  2. 2.
    Mansour T (2002) Chemotherapeutic targets in parasites: contemporary strategies. Cambridge University Press, New York, p 226Google Scholar
  3. 3.
    Cioli D, Valle C, Angelucci F et al (2008) Trends Parasitol 24:379PubMedCrossRefGoogle Scholar
  4. 4.
    Warren K (1988) The biology of parasitism. Englund PT, Sher A (eds) Alan R. Riss, New York, p 3Google Scholar
  5. 5.
    Halliwell B, Gutteridge J (2007) Free radicals in biology and medicine. Oxford University Press, Oxford, p 851Google Scholar
  6. 6.
    Muller S, Liebau E, Walter RD et al (2003) Trends Parasitol 19:320PubMedCrossRefGoogle Scholar
  7. 7.
    Simeonov A, Jadhav A, Sayed AA et al (2008) PLoS Negl Trop Dis 2:e127PubMedCrossRefGoogle Scholar
  8. 8.
    Toledano MB, Kumar C, Le Moan N et al (2007) FEBS Lett 581:3598PubMedCrossRefGoogle Scholar
  9. 9.
    Meyer Y, Buchanan BB, Vignols F et al (2009) Annu Rev Genet 43:335PubMedCrossRefGoogle Scholar
  10. 10.
    Lillig CH, Berndt C, Holmgren A (2008) Biochim Biophys Acta 1780:1304PubMedCrossRefGoogle Scholar
  11. 11.
    Rouhier N, Couturier J, Johnson MK et al (2009) Trends Biochem Sci 35:43PubMedCrossRefGoogle Scholar
  12. 12.
    Atkinson HJ, Babbitt PC (2009) PLoS Comput Biol 5:e1000541PubMedCrossRefGoogle Scholar
  13. 13.
    Holmgren A, Johansson C, Berndt C et al (2005) Biochem Soc Trans 33:1375PubMedCrossRefGoogle Scholar
  14. 14.
    Alger HM, Williams DL (2002) Mol Biochem Parasitol 121:129PubMedCrossRefGoogle Scholar
  15. 15.
    Agorio A, Chalar C, Cardozo S et al (2003) J Biol Chem 278:12920PubMedCrossRefGoogle Scholar
  16. 16.
    Rendon JL, Del Arenal IP, Guevara-Flores A et al (2004) Mol Biochem Parasitol 133:61PubMedCrossRefGoogle Scholar
  17. 17.
    Otero L, Bonilla M, Protasio AV et al (2010) BMC Genomics 11:237PubMedCrossRefGoogle Scholar
  18. 18.
    Angelucci F, Miele AE, Boumis G et al (2008) Proteins 72:936PubMedCrossRefGoogle Scholar
  19. 19.
    Angelucci F, Dimastrogiovanni D, Boumis G et al (2010) J Biol Chem 285:32557PubMedCrossRefGoogle Scholar
  20. 20.
    Bonilla M, Denicola A, Novoselov SV et al (2008) J Biol Chem 283:17898PubMedCrossRefGoogle Scholar
  21. 21.
    Bonilla M, Denicola A, Marino SM et al (2011) J Biol Chem 286:4959PubMedCrossRefGoogle Scholar
  22. 22.
    Berriman M, Haas BJ, LoVerde PT et al (2009) Nature 460:352PubMedCrossRefGoogle Scholar
  23. 23.
    Sun QA, Kirnarsky L, Sherman S et al (2001) Proc Natl Acad Sci USA 98:3673PubMedCrossRefGoogle Scholar
  24. 24.
    Kuntz AN, Davioud-Charvet E, Sayed AA et al (2007) PLoS Med 4:e206PubMedCrossRefGoogle Scholar
  25. 25.
    Martinez-Gonzalez JJ, Guevara-Flores A, Alvarez G et al (2010) Parasitol Res 107:227PubMedCrossRefGoogle Scholar
  26. 26.
    Sayed AA, Simeonov A, Thomas CJ et al (2008) Nat Med 14:407PubMedCrossRefGoogle Scholar
  27. 27.
    Williams DL, Pierce RJ, Cookson E et al (1992) Mol Biochem Parasitol 52:127PubMedCrossRefGoogle Scholar
  28. 28.
    Maiorino M, Roche C, Kiess M et al (1996) Eur J Biochem 238:838PubMedCrossRefGoogle Scholar
  29. 29.
    Mei H, LoVerde PT (1997) Exp Parasitol 86:69PubMedCrossRefGoogle Scholar
  30. 30.
    Mkoji GM, Smith JM, Prichard RK (1988) Int J Parasitol 18:661PubMedCrossRefGoogle Scholar
  31. 31.
    Zelck UE, Von Janowsky B (2004) Parasitology 128:493PubMedCrossRefGoogle Scholar
  32. 32.
    Taskov K, Chapple C, Kryukov GV et al (2005) Nucleic Acids Res 33:2227PubMedCrossRefGoogle Scholar
  33. 33.
    Lobanov AV, Delgado C, Rahlfs S et al (2006) Nucleic Acids Res 34:496PubMedCrossRefGoogle Scholar
  34. 34.
    Novoselov SV, Lobanov AV, Hua D et al (2007) Proc Natl Acad Sci USA 104:7857PubMedCrossRefGoogle Scholar
  35. 35.
    Lobanov AV, Gromer S, Salinas G et al (2006) Nucleic Acids Res 34:4012PubMedCrossRefGoogle Scholar
  36. 36.
    Aeby E, Palioura S, Pusnik M et al (2009) Proc Natl Acad Sci USA 106:5088PubMedCrossRefGoogle Scholar
  37. 37.
    Aeby E, Seidel V, Schneider A (2009) Mol Biochem Parasitol 168:191PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Gustavo Salinas
    • 1
  • Mariana Bonilla
    • 1
  • Lucía Otero
    • 1
  • Alexey V. Lobanov
    • 2
  • Vadim N. Gladyshev
    • 2
  1. 1.Cátedra de InmunologíaUniversidad de la República, Instituto de HigieneMontevideoUruguay
  2. 2.Division of Genetics, Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

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