Peroxiredoxin Systems of Protozoal Parasites

  • Marcel Deponte
  • Stefan Rahlfs
  • Katja Becker
Part of the Subcellular Biochemistry book series (SCBI, volume 44)

Abstract

Cellular redox metabolism is considered to be involved in the pathophysiology of diseases caused by protozoal parasites such as Toxoplasma, Trypanosoma, Leishmania, and Plasmodia. Redox reactions furthermore are thought to play a major role in the action of and the resistance to some clinically used antiparasitic drugs. Interestingly, in malarial parasites, the antioxidant enzymes catalase and glutathione peroxidase are absent which indicates a crucial role of the thioredoxin system in redox control. Besides a glutathione peroxidase-like thioredoxin peroxidase and a glutathione S-transferase with slight peroxidase activity, Plasmodium falciparum (the causative agent of tropical malaria) possesses four classical peroxiredoxins: Two peroxiredoxins of the typical 2-Cys Prx class, one 1-Cys peroxiredoxin with homology to the atypical 2-Cys Prx class, and a peroxiredoxin of the 1-Cys Prx class have been identified and partially characterized

∈dent In our article we give an introduction to redox-based drug development strategies against protozoal parasites and summarize the present knowledge on peroxiredoxin systems in Plasmodium

Keywords

Drug development Malaria Oxidative stress Peroxiredoxin Plasmodium Protozoal parasite 

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References

  1. Abe, K., Saito, H., 2000, Amyloid ß neurotoxicity not mediated by the mitogen-activated protein kinase cascade in cultured rat hippocampal and cortical neurons. Neurosci. Lett. 292: 1–4.CrossRefPubMedGoogle Scholar
  2. Akerman, S.E., Müller, S., 2003, 2-Cys peroxiredoxin PfTrx-Px1 is involved in the antioxidant defence of Plasmodium falciparum. Mol. Biochem. Parasitol. 130: 75–81.CrossRefPubMedGoogle Scholar
  3. Akerman, S.E., Müller, S., 2005, Peroxiredoxin-linked detoxification of hydroperoxides in Toxoplasma gondii. J. Biol. Chem. 280: 564–570.PubMedGoogle Scholar
  4. Atamna, H., Ginsburg, H., 1995, Heme degradation in the presence of glutathione: a proposed mechanism to account for the high levels of non-heme iron found in the membranes of hemoglobinopathic red blood cells. J. Biol. Chem. 270: 24876–24883.CrossRefPubMedGoogle Scholar
  5. Becker, K., Tilley, L., Vennerstrom, J.L., Roberts, D., Rogerson, S., Ginsburg, H., 2004, Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions. Int. J. Parasitol. 34: 163–189.CrossRefPubMedGoogle Scholar
  6. Biteau, B., Labarre, J., Toledano, M. B., 2003, ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature 425: 980–984.CrossRefPubMedGoogle Scholar
  7. Clarebout, G., Slomianny, C., Delcourt, P., Leu, B., Masset, A., Camus, D., Dive, D., 1998, Status of Plasmodium falciparum towards catalase. Br. J. Haematol. 103: 52–59.CrossRefPubMedGoogle Scholar
  8. Deponte, M., Becker, K., 2005a, Glutathione S-transferase from malarial parasites: structural and functional aspects. Methods Enzymol. 401: 241–253.CrossRefPubMedGoogle Scholar
  9. Deponte, M., Becker, K., 2005b, Biochemical characterization of Toxoplasma gondii 1-Cys peroxiredoxin 2 with mechanistic similarities to typical 2-Cys Prx. Mol. Biochem. Parasitol. 140: 87–96.CrossRefGoogle Scholar
  10. Deponte, M., Becker, K., Rahlfs, S., 2005, Plasmodium falciparum glutaredoxin-like proteins. Biol. Chem. 386: 33–40.CrossRefPubMedGoogle Scholar
  11. Ding, M., Kwok, L.Y., Schlüter, D., Clayton, C., Soldati, D., 2004, The antioxidant systems in Toxoplasma gondii and the role of cytosolic catalase in defence against oxidative injury. Mol. Microbiol. 51: 47–61.PubMedGoogle Scholar
  12. Egan, T.J., Combrinck, J.M., Egan, J., Hearne, G.R., Marques, H.M., Ntenteni, S., Sewell, B. T., Smith, P.J., Taylor, D., van Schalkwyk, D.A., Walden, J.C., 2002, Fate of haem iron in the malaria parasite Plasmodium falciparum. Biochem. J. 365: 343–347.CrossRefPubMedGoogle Scholar
  13. Flohé, L., Jaeger, T., Pilawa, S., Sztajer, H., 2003, Thiol-dependent peroxidases care little about homology-based assignments of function. Redox Rep. 8: 256–264.CrossRefPubMedGoogle Scholar
  14. Ginsburg, H., Famin, O., Zhang, J., Krugliak, M., 1998, Inhibition of glutathione-dependent degradation of heme by chloroquine and amodiaquine as a possible basis for their antimalarial mode of action. Biochem. Pharmacol. 56: 1305–1313.CrossRefPubMedGoogle Scholar
  15. Hiller, N., Fritz-Wolf, K., Deponte, M., Wende, W., Zimmermann, H., Becker, K., 2006, Plasmodium falciparum glutathione S-transferase – structural and mechanistic studies on ligand binding and enzyme inhibition. Protein Sci. 15: 281–289.CrossRefPubMedGoogle Scholar
  16. Hofmann, B., Hecht, H. J., Flohé, L., 2002, Peroxiredoxins. Biol. Chem. 383: 347–364.CrossRefPubMedGoogle Scholar
  17. Jang, H.H., Lee, K.O., Chi, Y.H., Jung, B.G., Park, S.K., Park, J.H., Lee, J.R., Lee, S.S., Moon, J.C., Yun, J.W., Choi, Y.O., Kim, W.Y., Kang, J.S., Cheong, G.W., Yun, D.J., Rhee, S.G., Cho, M.J., Lee, S.Y., 2004, Two enzymes in one; two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell 117: 625–635.CrossRefPubMedGoogle Scholar
  18. Jensen, R.A., 2001, Orthologs and paralogs - we need to get it right. Genome Biol. 2: 1002.CrossRefGoogle Scholar
  19. Jeong, W., Park, S.J., Chang, T.S., Lee, D.Y., Rhee, S.G., 2006, Molecular mechanism of the reduction of cysteine sulfinic acid of peroxiredoxin to cysteine by mammalian sulfiredoxin. J. Biol. Chem. 281:14400–14407.CrossRefPubMedGoogle Scholar
  20. Kawazu, S., Komaki, K., Tsuji, N., Kawai, S., Ikenoue, N., Hatabu, T., Ishikawa, H., Matsumoto, Y., Himeno, K., Kano S., 2001, Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 116: 73–79.CrossRefPubMedGoogle Scholar
  21. Kawazu, S., Nozaki, T., Tsuboi, T., Nakano, Y., Komaki-Yasuda, K., Ikenoue, N., Torii, M., Kano, S., 2003, Expression profiles of peroxiredoxin proteins of the rodent malaria parasite Plasmodium yoelii. Int. J. Parasitol. 33: 1455–1461.CrossRefPubMedGoogle Scholar
  22. Kawazu, S., Ikenoue, N., Takemae, H., Komaki-Yasuda, K., Kano, S., 2005, Roles of 1-Cys peroxiredoxin in haem detoxification in the human malaria parasite Plasmodium falciparum. FEBS J. 272: 1784–1791.CrossRefPubMedGoogle Scholar
  23. Komaki-Yasuda, K., Kawazu, S., Kano, S., 2003, Disruption of the Plasmodium falciparum 2-Cys peroxiredoxin gene renders parasites hypersensitive to reactive oxygen and nitrogen species. FEBS Lett. 547: 140–144.CrossRefPubMedGoogle Scholar
  24. Krauth-Siegel, R.L., Bauer, H., Schirmer, R.H., 2005, Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. Angew. Chem. Int. Ed. Engl. 44: 690–715.CrossRefPubMedGoogle Scholar
  25. Krauth-Siegel, R.L., Meiering, S.K., Schmidt, H., 2003, The parasite-specific trypanothione metabolism of trypanosoma and leishmania. Biol. Chem. 384:539–49.CrossRefPubMedGoogle Scholar
  26. Loria, P., Miller, S., Foley, M., Tilley, L., 1999, Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials. Biochem. J. 339:363–370.CrossRefPubMedGoogle Scholar
  27. Müller, S., 2004, Redox and antioxidant systems of the malaria parasite Plasmodium falciparum. Mol. Microbiol. 53:1291–1305.CrossRefPubMedGoogle Scholar
  28. Müller, S., Liebau, E., Walter, R.D., Krauth-Siegel, R.L., 2003, Thiol-based redox metabolism of protozoan parasites. Trends Parasitol. 19: 320–328.CrossRefPubMedGoogle Scholar
  29. Nickel, C., Rahlfs, S., Deponte, M., Koncarevic, S., Becker, K. 2006, Thioredoxin networks in the malarial parasite Plasmodium falciparum. Antioxid. Redox Signal. 8: 1227–1239.CrossRefPubMedGoogle Scholar
  30. Nickel, C., Trujillo, M., Rahlfs, S., Deponte, M., Radi, R., Becker, K., 2005, Plasmodium falciparum 2-Cys peroxiredoxin reacts with plasmoredoxin and peroxynitrite. Biol. Chem. 386: 1129–1136.CrossRefPubMedGoogle Scholar
  31. Rahlfs, S., Becker, K., 2001, Thioredoxin peroxidases of the malarial parasite Plasmodium falciparum. Eur. J. Biochem. 268: 1404–1409.CrossRefPubMedGoogle Scholar
  32. Rahlfs, S., Becker, K., 2006, Interference with redox-active enzymes as a basis for the design of antimalarial drugs. Mini Rev. Med. Chem. 6: 163–176.CrossRefPubMedGoogle Scholar
  33. Rahlfs, S., Schirmer, R.H., Becker, K., 2002, The thioredoxin system of Plasmodium falciparum and other parasites. Cell. Mol. Life Sci. 59:1024–1041.CrossRefPubMedGoogle Scholar
  34. Roos, D.S., Crawford, M.J., Donald, R.G.K., Fraunholz, M., Harb, O.S., He, C.Y., Kissinger, J.C., Shaw, M.K., Striepen, B., 2002, Mining the Plasmodium genome database to define organellar function: what does the apicoplast do? Phil. Trans. R. Soc. Lond. 357: 35–46.CrossRefGoogle Scholar
  35. Sarma, G.N., Nickel, C., Rahlfs, S., Fischer, M., Becker, K., Karplus, P.A., 2005, Crystal structure of a novel Plasmodium falciparum 1-Cys peroxiredoxin. J. Mol. Biol. 346: 1021–1034.CrossRefPubMedGoogle Scholar
  36. Sztajer, H., Gamain, B., Aumann, K. D., Slomianny, C., Becker, K., Brigelius-Flohé, R., Flohé, L., 2001, The putative glutathione peroxidase gene of Plasmodium falciparum codes for a thioredoxin peroxidase. J. Biol. Chem. 276: 7397–7403.CrossRefPubMedGoogle Scholar
  37. Veal, E.A., Findlay, V.J., Day, A.M., Bozonet, S.M., Evans, J.M., Quinn, J., Morgan, B.A., 2004, A 2-Cys peroxiredoxin regulates peroxide-induced oxidation and activation of a stress-activated MAP kinase. Mol. Cell. 15:129–139.CrossRefPubMedGoogle Scholar
  38. Wilkinson, S.R., Meyer, D.J., Taylor, M.C., Bromley, E.V., Miles, M.A., Kelly, J.M., 2002, The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin. J. Biol. Chem. 277:17062–17071.CrossRefPubMedGoogle Scholar
  39. Wood, Z.A., Schröder, E., Harris, J.R, Poole, L.B. 2003a, Structure, mechanism and regulation of peroxiredoxins. Trends Biochem. Sci. 28: 32–40.CrossRefPubMedGoogle Scholar
  40. Wood, Z. A., Poole, L. B. and Karplus, P. A., 2003b, Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300: 650–653.CrossRefGoogle Scholar
  41. Yano, K., Komaki-Yasuda, K., Kobayashi, T., Takemae, H., Kita, K., Kano, S., Kawazu, S., 2005, Expression of mRNAs and proteins for peroxiredoxins in Plasmodium falciparum erythrocytic stage. Parasitol. Int. 54: 35–41.CrossRefPubMedGoogle Scholar
  42. Yano, K., Komaki-Yasuda, K,, Tsuboi, T., Torii, M., Kano, S., Kawazu, S.I., 2006, 2-Cys Peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium berghei. Mol. Biochem. Parasitol. 148: 44–51.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Marcel Deponte
    • 1
  • Stefan Rahlfs
    • 1
  • Katja Becker
    • 1
  1. 1.Interdisciplinary Research CenterJustus Liebig UniversityHeinrich-Buff-Ring 26–32Germany

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