Skip to main content
SpringerLink
Log in

The Trypanothione System

  • Chapter
Peroxiredoxin Systems

Part of the book series: Subcellular Biochemistry ((SCBI,volume 44))

Abstract

Trypanosomes and Leishmania, the causative agents of severe tropical diseases, employ 2-Cys-peroxiredoxins together with cysteine-homologues of glutathione peroxidases and ascorbate-dependent peroxidases for the detoxification of hydroperoxides. All three types of peroxidases gain their reducing equivalents from the parasite-specific dithiol trypanothione [bis(glutathionyl)spermidine]. Based on their primary structure and cellular localization, the trypanosomatid 2-Cys-peroxiredoxins are subdivided into two families that occur in the mitochondrion and cytosol of the parasites. In Trypanosoma brucei, the cytosolic 2-Cys-peroxiredoxin, as well as the glutathione peroxidase-type enzyme, is essential for cell viability. Despite overlapping substrate specificities and subcellular localizations, the two types of peroxidases can obviously not substitute for each other which suggests distinct cell-physiological roles

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adak, S., Datta, A.K., 2005, Leishmania major encodes an unusual peroxidase that is a close homologue of plant ascorbate peroxidase: a novel role of the transmembrane domain. Biochem. J. 390: 465–474.

    Article  PubMed  CAS  Google Scholar 

  • Alphey, M.S., Leonard, G.A., Gourley, D.G., Tetaud, E., Fairlamb, A.H., Hunter, W.N., 1999, The high resolution crystal structure of recombinant Crithidia fasciculata tryparedoxin-I. J. Biol. Chem. 274: 25613–25622.

    Article  PubMed  CAS  Google Scholar 

  • Alphey, M.S., Bond, C.S., Tetaud, E., Fairlamb, A.H., Hunter, W.N., 2000, The structure of reduced tryparedoxin peroxidase reveals a decamer and insight into reactivity of 2 Cys-peroxiredoxins. J. Mol. Biol. 300: 903–916.

    Article  PubMed  CAS  Google Scholar 

  • Alphey, M.S., Gabrielsen, M., Micossi, E., Leonard, G.A., McSweeney, S.M., Ravelli, R.B., Tetaud, E., Fairlamb, A.H., Bond, C.S., Hunter, W.N., 2003, Tryparedoxins from Crithidia fasciculata and Trypanosoma brucei: photoreduction of the redox disulfide using synchrotron radiation and evidence for a conformational switch implicated in function. J. Biol. Chem. 278: 25919–25925.

    Article  PubMed  CAS  Google Scholar 

  • Ariyanayagam, M.R., Fairlamb, A.H., 1999, Entamoeba histolytica lacks trypanothione metabolism. Mol. Biochem. Parasitol. 103: 61–69.

    Article  PubMed  CAS  Google Scholar 

  • Ariyanayagam, M.R., Fairlamb, A.H., 2001, Ovothiol and trypanothione as antioxidants in trypanosomatids. Mol. Biochem. Parasitol. 115:189–198.

    Article  PubMed  CAS  Google Scholar 

  • Ariyanayagam, M.R., Oza, S.L., Guther, M.L., Fairlamb, A.H., 2005, Phenotypic analysis of trypanothione synthetase knockdown in the African trypanosome. Biochem. J. 391: 425–432.

    Article  PubMed  CAS  Google Scholar 

  • Ariza, A., Vickers, T. J., Greig, N., Armour, K. A., Dixon, M. J., Eggleston, I. M., Fairlamb, A. H., Bond, C. S., 2006, Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme. Mol. Microbiol. 59:1239–1248.

    Article  PubMed  CAS  Google Scholar 

  • Awad, S., Henderson, G. B., Cerami, A., Held, K. D., 1992, Effects of trypanothione on the biological activity of irradiated transforming DNA. Int. J. Radiat. Biol. 62: 401–407.

    Article  PubMed  CAS  Google Scholar 

  • Barr, S. D., and Gedamu, L., 2003, Role of peroxidoxins in Leishmania chagasi survival. Evidence of an enzymatic defense against nitrosative stress. J. Biol. Chem. 278:10816–10823.

    Article  PubMed  CAS  Google Scholar 

  • Berriman, M., Ghedin, E., Hertz-Fowler, C., Blandin, G., Renauld, H., Bartholomeu, D.C., et al., 2005, The genome of the African trypanosome Trypanosoma brucei. Science 309: 416–422.

    Article  PubMed  CAS  Google Scholar 

  • Biteau, B., Labarre, J., Toledano, M.B., 2003, ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature 425: 980–984.

    Article  PubMed  CAS  Google Scholar 

  • Bollinger, J.M., Kwon, D.S., Huisman, G.W., Kolters, R., Walsh, C.T., 1995, Glutathionylspermidine metabolism in Escherichia coli. Purification, cloning, overproduction, and characterization of a bifunctional glutathionylspermidine synthetase/amidase. J. Biol. Chem. 270: 14031–14041.

    Article  PubMed  CAS  Google Scholar 

  • Budde, H., Flohé, L., Hecht, H.J., Hofmann, B., Stehr, M., Wissing, J., Lünsdorf, H., 2003a, Kinetics and redox-sensitive oligomerisation reveal negative subunit cooperativity in tryparedoxin peroxidase of Trypanosoma brucei brucei. Biol. Chem. 384: 619–633.

    Article  CAS  Google Scholar 

  • Budde, H., Flohé, L., Hofmann, B., Nimtz, M., 2003b, Verification of the interaction of a tryparedoxin peroxidase with tryparedoxin by ESI-MS/MS. Biol. Chem. 384: 1305–1309.

    Article  CAS  Google Scholar 

  • Carnieri, E.G., Moreno, S.N., Docampo, R., 1993, Trypanothione-dependent peroxide metabolism in Trypanosoma cruzi different stages. Mol. Biochem. Parasitol. 61: 79–86.

    Article  PubMed  CAS  Google Scholar 

  • Carter, K.C., Sundar, S., Spickett, C., Pereira, O.C., Mullen, A.B., 2003, The in vivo susceptibility of Leishmania donovani to sodium stibogluconate is drug specific and can be reversed by inhibiting glutathione biosynthesis. Antimicrob. Agents Chemother. 47: 1529–1535.

    Article  PubMed  CAS  Google Scholar 

  • Castro, H., Budde, H., Flohé, L., Hofmann, B., Lünsdorf, H., Wissing, J., Tomas, A.M., 2002a, Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania infantum. Free Radic. Biol. Med. 33: 1563–1574.

    Article  CAS  Google Scholar 

  • Castro, H., Sousa, C., Santos, M., Cordeiro-da-Silva, A., Flohé, L., Tomas, A.M., 2002b, Complementary antioxidant defense by cytoplasmic and mitochondrial peroxiredoxins in Leishmania infantum. Free Radic. Biol. Med. 33: 1552–1562.

    Article  CAS  Google Scholar 

  • Chang, T.S., Jeong, W., Choi, S.Y., Yu, S., Kang, S.W., Rhee, S.G., 2002, Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation. J. Biol. Chem. 277: 25370–25376.

    Article  PubMed  CAS  Google Scholar 

  • Comini, M., Menge, U., and Flohé, L., 2003, Biosynthesis of trypanothione in Trypanosoma brucei brucei. Biol. Chem. 384: 653–656.

    Article  PubMed  CAS  Google Scholar 

  • Comini, M.A., Guerrero, S.A., Haile, S., Menge, U., Lünsdorf, H., Flohé, L., 2004, Validation of Trypanosoma brucei trypanothione synthetase as drug target. Free Radic. Biol. Med. 36: 1289–1302.

    Article  PubMed  CAS  Google Scholar 

  • Comini, M., Menge, U., Wissing, J., Flohé, L., 2005, Trypanothione synthesis in crithidia revisited. J. Biol. Chem. 280: 6850–6860.

    Article  PubMed  CAS  Google Scholar 

  • Delaunay, A., Pflieger, D., Barrault, M.B., Vinh, J., Toledano, M.B., 2002, A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell 111: 471–481.

    Article  PubMed  CAS  Google Scholar 

  • Dormeyer, M., Reckenfelderbäumer, N., Lüdemann, H., Krauth-Siegel, R.L., 2001, Trypanothione-dependent synthesis of deoxyribonucleotides by Trypanosoma brucei ribonucleotide reductase. J. Biol. Chem. 276: 10602–10606.

    Article  PubMed  CAS  Google Scholar 

  • El-Sayed, N.M., Myler, P.J., Bartholomeu, D.C., Nilsson, D., Aggarwal, G., et al., 2005, The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 309: 409–415.

    Article  PubMed  CAS  Google Scholar 

  • Fairlamb, A.H., Blackburn, P., Ulrich, P., Chait, B.T., Cerami, A., 1985, Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 227: 1485–1487.

    Article  PubMed  CAS  Google Scholar 

  • Fairlamb, A.H., Henderson, G.B., Cerami, A., 1989, Trypanothione is the primary target for arsenical drugs against African trypanosomes. Proc. Natl. Acad. Sci. USA 86: 2607–2611.

    Article  PubMed  CAS  Google Scholar 

  • Fairlamb, A.H., Cerami, A., 1992, Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol. 46: 695–729.

    Article  PubMed  CAS  Google Scholar 

  • Flohé L., Brigelius-Flohé R., 2001, Selenoproteins of the glutathione system. In: L. Hatfield (ed.), Selenium, its Molecular Biology and Role in Human Health, Kluwer Academic Publishers, Boston, Dordrecht, London, pp.157–178.

    Google Scholar 

  • Flohé, L., Loschen, G., Günzler, W.A., Eichele, E., 1972, Glutathione peroxidase, V. The kinetic mechanism. Hoppe Seylers Z. Physiol. Chem. 353: 987–999.

    PubMed  Google Scholar 

  • Flohé, L., Hecht, H.J., Steinert, P., 1999, Glutathione and trypanothione in parasitic hydroperoxide metabolism. Free Radic. Biol. Med. 27: 966–984.

    Article  PubMed  Google Scholar 

  • Flohé, L., Budde, H., Bruns, K., Castro, H., Clos, J., Hofmann, B., Kansal-Kalavar, S., Krumme, D., Menge, U., Plank-Schumacher, K., Sztajer, H., Wissing, J., Wylegalla, C., Hecht, H.J., 2002, Tryparedoxin peroxidase of Leishmania donovani: molecular cloning, heterologous expression, specificity, and catalytic mechanism. Arch. Biochem. Biophys. 397: 324–335.

    Article  PubMed  CAS  Google Scholar 

  • Gilbert, H.F., 1990, Molecular and cellular aspects of thiol-disulfide exchange. Adv. Enzymol. Relat. Areas Mol. Biol. 63: 69–172.

    PubMed  CAS  Google Scholar 

  • Gommel, D.U., Nogoceke, E., Morr, M., Kiess, M., Kalisz, H.M., Flohé, L., 1997, Catalytic characteristics of tryparedoxin. Eur. J. Biochem. 248: 913–918.

    Article  PubMed  CAS  Google Scholar 

  • Grondin, K., Haimeur, A., Mukhopadhyay, R., Rosen, B.P., Ouellette, M., 1997, Co-amplification of the gamma-glutamylcysteine synthetase gene gsh1 and of the ABC transporter gene pgpA in arsenite-resistant Leishmania tarentolae. Embo J. 16: 3057–3065.

    Article  PubMed  CAS  Google Scholar 

  • Guerrero, S.A., Lopez, J.A., Steinert, P., Montemartini, M., Kalisz, H.M., Colli, W., Singh, M., Alves, M.J., Flohé, L., 2000, His-tagged tryparedoxin peroxidase of Trypanosoma cruzi as a tool for drug screening. Appl. Microbiol. Biotechnol. 53: 410–414.

    Article  PubMed  CAS  Google Scholar 

  • Haimeur, A., Brochu, C., Genest, P., Papadopoulou, B., Ouellette, M., 2000, Amplification of the ABC transporter gene PGPA and increased trypanothione levels in potassium antimonyl tartrate (SbIII) resistant Leishmania tarentolae. Mol. Biochem. Parasitol. 108: 131–135.

    Article  PubMed  CAS  Google Scholar 

  • Henderson, G.B., Yamaguchi, M., Novoa, L., Fairlamb, A.H., Cerami, A., 1990, Biosynthesis of the trypanosomatid metabolite trypanothione: purification and characterization of trypanothione synthetase from Crithidia fasciculata. Biochemistry 29: 3924–3929.

    Article  PubMed  CAS  Google Scholar 

  • Hillebrand, H., Schmidt, A., Krauth-Siegel, R.L., 2003, A second class of peroxidases linked to the trypanothione metabolism. J. Biol. Chem. 278: 6809–6815.

    Article  PubMed  CAS  Google Scholar 

  • Hirotsu, S., Abe, Y., Okada, K., Nagahara, N., Hori, H., Nishino, T., Hakoshima, T., 1999, Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein 23kDa/proliferation-associated gene product. Proc. Natl. Acad. Sci. USA 96: 12333–12338.

    Article  PubMed  CAS  Google Scholar 

  • Hofmann, B., Hecht, H.J. Flohé, L., 2002, Peroxiredoxins. Biol. Chem. 383: 347–364.

    Article  PubMed  CAS  Google Scholar 

  • Irsch, T., Krauth-Siegel, R.L., 2004, Glyoxalase II of African trypanosomes is trypanothione-dependent. J. Biol. Chem. 279: 22209–22217.

    Article  PubMed  CAS  Google Scholar 

  • Ivens, A.C., Peacock, C.S., Worthey, E.A., Murphy, L., Aggarwal, G., Berriman, M., et al., 2005, The genome of the kinetoplastid parasite, Leishmania major. Science 309: 436–442.

    Article  PubMed  Google Scholar 

  • Jung, B.G., Lee, K.O., Lee, S.S., Chi, Y.H., Jang, H.H., Kang, S.S., Lee, K., Lim, D., Yoon, S.C., Yun, D.J., Inoue, Y., Cho, M.J., Lee, S.Y., 2002, A Chinese cabbage cDNA with high sequence identity to phospholipid hydroperoxide glutathione peroxidases encodes a novel isoform of thioredoxin-dependent peroxidase. J. Biol. Chem. 277: 12572–12578.

    Article  PubMed  CAS  Google Scholar 

  • Koenig, K., Menge, U., Kiess, M., Wray, V., Flohé, L., 1997, Convenient isolation and kinetic mechanism of glutathionylspermidine synthetase from Crithidia fasciculata. J. Biol. Chem. 272: 11908–11915.

    Article  PubMed  CAS  Google Scholar 

  • Krauth-Siegel, R.L., Lüdemann, H., 1996, Reduction of dehydroascorbate by trypanothione. Mol. Biochem. Parasitol. 80: 203–208.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Levick, M.P., Tetaud, E., Fairlamb, A.H., Blackwell, J.M., 1998, Identification and characterisation of a functional peroxidoxin from Leishmania major. Mol. Biochem. Parasitol. 96: 125–137.

    Article  PubMed  CAS  Google Scholar 

  • Lin, Y.C., Hsu, J.Y., Chiang, S.C., Lee, S.T., 2005, Distinct overexpression of cytosolic and mitochondrial tryparedoxin peroxidases results in preferential detoxification of different oxidants in arsenite-resistant Leishmania amazonensis with and without DNA amplification. Mol. Biochem. Parasitol. 142: 66–75.

    Article  PubMed  CAS  Google Scholar 

  • Lopez J.A., Carvalho T.U., de Souza W., Flohé L., Guerrero S.A., Montemartini M., Kalisz H.M., Nogoceke E., Singh M., Alves M.J., Colli W., 2000, Evidence for a trypanothione-dependent peroxidase system in Trypanosoma cruzi. Free Radic. Biol. Med. 28: 767–772.

    Article  PubMed  CAS  Google Scholar 

  • Lüdemann, H., Dormeyer, M., Sticherling, C., Stallmann, D., Follmann, H., Krauth-Siegel, R.L., 1998, Trypanosoma brucei tryparedoxin, a thioredoxin-like protein in African trypanosomes. FEBS Lett. 431: 381–385..

    Article  PubMed  Google Scholar 

  • Maiorino, M., Ursini, F., Bosello, V., Toppo, S., Tosatto, S.C., Mauri, P., Becker, K., Roveri, A., Bulato, C., Benazzi, L., De Palma, A., Flohé, L., 2007, The thioredoxin specificity of Drosophila GPx: A paradigm for a peroxiredoxin-like mechanism of many glutathione peroxidases. J. Mol. Biol. 365: 1033–1046.

    Article  PubMed  CAS  Google Scholar 

  • Maya, J.D., Bollo, S., Nunez-Vergara, L.J., Squella, J.A., Repetto, Y., Morello, A., Perie, J., Chauviere, G., 2003, Trypanosoma cruzi: effect and mode of action of nitroimidazole and nitrofuran derivatives. Biochem. Pharmacol. 65: 999–1006.

    Article  PubMed  CAS  Google Scholar 

  • Montemartini, M., Nogoceke, E., Singh, M., Steinert, P., Flohé, L., Kalisz, H.M., 1998, Sequence analysis of the tryparedoxin peroxidase gene from Crithidia fasciculata and its functional expression in Escherichia coli. J. Biol. Chem. 273: 4864–4871.

    Article  PubMed  CAS  Google Scholar 

  • Montemartini, M., Kalisz, H.M., Hecht, H.J., Steinert, P., Flohé, L., 1999, Activation of active-site cysteine residues in the peroxiredoxin-type tryparedoxin peroxidase of Crithidia fasciculata. Eur. J. Biochem. 264: 516–524.

    Article  PubMed  CAS  Google Scholar 

  • Montrichard, F., Le Guen, F., Laval-Martin, D.L., Davioud-Charvet, E., 1999, Evidence for the co-existence of glutathione reductase and trypanothione reductase in the non-trypanosomatid Euglenozoa: Euglena gracilis Z. FEBS Lett. 442: 29–33.

    Article  PubMed  CAS  Google Scholar 

  • Motyka, S.A., Drew, M.E., Yildirir, G., Englund, P.T., 2006, Over-expression of a cytochrome B5 reductase-like protein causes kinetoplast DNA loss in Trypanosoma brucei. J. Biol. Chem. In press, PMID: 16690608.

    Google Scholar 

  • Moutiez, M., Meziane-Cherie, D., Aumercier, M., Sergheraert, C., Tartar, A., 1994, Compared reactivities of trypanothione and glutathione in conjugation reactions. Chem. Pharm. Bull. 42: 2641–2644.

    CAS  Google Scholar 

  • Mukhopadhyay, R., Dey, S., Xu, N., Gage, D., Lightbody, J., Ouellette, M., Rosen, B.P., 1996, Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Proc. Natl. Acad. Sci. USA 93: 10383–10387.

    Article  PubMed  CAS  Google Scholar 

  • Müller, S., Liebau, E., Walter, R.D., Krauth-Siegel, R.L., 2003, Thiol-based redox metabolism of protozoan parasites. Trends Parasitol. 19: 320–328.

    Article  PubMed  CAS  Google Scholar 

  • Nogoceke, E., Gommel, D.U., Kiess, M., Kalisz, H.M., Flohé, L., 1997, A unique cascade of oxidoreductases catalyses trypanothione-mediated peroxide metabolism in Crithidia fasciculata. Biol. Chem. 378: 827–836.

    Article  PubMed  CAS  Google Scholar 

  • Ondarza, R.N., Tamayo, E.H., Hurtado, G., Hernandez, E., Iturbe, A., 1997, Isolation and purification of glutathionyl-spermidine and trypanothione from Entamoeba histolytica. Arch. Med. Res. 28: 73–75.

    PubMed  CAS  Google Scholar 

  • Ondarza, R.N., Hurtado, G., Iturbe, A., Hernandez, E., Tamayo, E., Woolery, M., 2005, Identification of trypanothione from the human pathogen Entamoeba histolytica by mass spectrometry and chemical analysis. Biotechnol. Appl. Biochem. 42: 175–181.

    Article  PubMed  CAS  Google Scholar 

  • Onn, I., Milman-Shtepel, N., Shlomai, J., 2004, Redox potential regulates binding of universal minicircle sequence binding protein at the kinetoplast DNA replication origin. Eukaryot. Cell 3: 277–287.

    Article  PubMed  CAS  Google Scholar 

  • Oza, S.L., Ariyanayagam, M.R., Fairlamb, A.H., 2002a, Characterization of recombinant glutathionylspermidine synthetase/amidase from Crithidia fasciculata. Biochem. J. 364: 679–686.

    Article  CAS  Google Scholar 

  • Oza, S.L., Tetaud, E., Ariyanayagam, M.R., Warnon, S.S., and Fairlamb, A.H., 2002b, A single enzyme catalyses formation of trypanothione from glutathione and spermidine in Trypanosoma cruzi. J. Biol. Chem. 277: 35853–35861.

    Article  CAS  Google Scholar 

  • Oza, S.L., Ariyanayagam, M.R., Aitcheson, N., Fairlamb, A.H., 2003, Properties of trypanothione synthetase from Trypanosoma brucei. Mol. Biochem. Parasitol. 131: 25–33.

    Article  PubMed  CAS  Google Scholar 

  • Oza, S.L., Shaw, M.P., Wyllie, S., Fairlamb, A.H., 2005, Trypanothione biosynthesis in Leishmania major. Mol. Biochem. Parasitol. 139: 107–116.

    Article  PubMed  CAS  Google Scholar 

  • Padmanabhan, P.K., Mukherjee, A., Singh, S., Chattopadhyaya, S., Gowri, V.S., Myler, P.J., Srinivasan, N., Madhubala, R., 2005, Glyoxalase I from Leishmania donovani: a potential target for anti-parasite drug. Biochem. Biophys. Res. Commun. 337:1237–1248.

    Article  PubMed  CAS  Google Scholar 

  • Padmanabhan, P.K., Mukherjee, A., Madhubala, R., 2006, Characterization of the gene encoding glyoxalase II from Leishmania donovani: a potential target for anti-parasite drugs. Biochem. J. 393: 227–234.

    Article  PubMed  CAS  Google Scholar 

  • Pineyro, M.D., Pizarro, J.C., Lema, F., Pritsch, O., Cayota, A., Bentley, G.A., Robello, C., 2005, Crystal structure of the tryparedoxin peroxidase from the human parasite Trypanosoma cruzi. J. Struct. Biol. 150: 11–22.

    Article  PubMed  CAS  Google Scholar 

  • Reckenfelderbäumer, N., Krauth-Siegel, R.L., 2002, Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. J. Biol. Chem. 277: 17548–17555.

    Article  PubMed  CAS  Google Scholar 

  • Repetto, Y., Opazo, E., Maya, J.D., Agosin, M., Morello, A., 1996, Glutathione and trypanothione in several strains of Trypanosoma cruzi: effect of drugs. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 115: 281–285.

    Article  PubMed  CAS  Google Scholar 

  • Rhee, S.G., Chae, H.Z., Kim, K., 2005, Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic. Biol. Med. 38: 1543–1552.

    Article  PubMed  CAS  Google Scholar 

  • Schlecker, T., Schmidt, A., Dirdjaja, N., Voncken, F., Clayton, C., Krauth-Siegel, R.L., 2005, Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei. J. Biol. Chem. 280: 14385–14394.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, H., Krauth-Siegel, R.L., 2003, Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei. J. Biol. Chem. 278: 46329–46336.

    Article  PubMed  CAS  Google Scholar 

  • Schröder, E., Littlechild, J.A., Lebedev, A.A., Errington, N., Vagin, A.A., Isupov, M.N., 2000, Crystal structure of decameric 2-Cys peroxiredoxin from human erythrocytes at 1.7 A resolution. Structure Fold Des. 8: 605–615.

    Article  PubMed  Google Scholar 

  • Shahi, S.K., Krauth-Siegel, R.L., Clayton, C.E., 2002, Overexpression of the putative thiol conjugate transporter TbMRPA causes melarsoprol resistance in Trypanosoma brucei. Mol. Microbiol. 43: 1129–1138.

    Article  PubMed  CAS  Google Scholar 

  • Shim, H., Fairlamb, A.H., 1988, Levels of polyamines, glutathione and glutathione-spermidine conjugates during growth of the insect trypanosomatid Crithidia fasciculata. J. Gen. Microbiol. 134: 807–817.

    PubMed  CAS  Google Scholar 

  • Steenkamp, D.J., 2002, Thiol metabolism of the trypanosomatids as potential drug targets. IUBMB Life 53: 243–248.

    Article  PubMed  CAS  Google Scholar 

  • Steinert, P., Plank-Schumacher, K., Montemartini, M., Hecht, H.J., Flohé, L., 2000, Permutation of the active site motif of tryparedoxin 2. Biol. Chem. 381: 211–219.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Tabor, H., Tabor, C.W., 1975, Isolation, characterization, and turnover of glutathionylspermidine from Escherichia coli. J. Biol. Chem. 250: 2648–2654.

    PubMed  CAS  Google Scholar 

  • Tanaka, T., Izawa, S., Inoue, Y., 2005, GPX2, encoding a phospholipid hydroperoxide glutathione peroxidase homologue, codes for an atypical 2-Cys peroxiredoxin in Saccharomyces cerevisiae. J. Biol. Chem. 280: 42078–42087.

    Article  PubMed  CAS  Google Scholar 

  • Tetaud, E., Giroud, C., Prescott, A.R., Parkin, D.W., Baltz, D., Biteau, N., Baltz, T., Fairlamb, A.H., 2001, Molecular characterisation of mitochondrial and cytosolic trypanothione-dependent tryparedoxin peroxidases in Trypanosoma brucei. Mol. Biochem. Parasitol. 116: 171–183.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, L., Denicola, A., Radi, R., 2003, The trypanothione-thiol system in Trypanosoma cruzi as a key antioxidant mechanism against peroxynitrite-mediated cytotoxicity. Arch. Biochem. Biophys. 412: 55–64.

    Article  PubMed  CAS  Google Scholar 

  • Trujillo, M., Budde, H., Pineyro, M.D., Stehr, M., Robello, C., Flohè, L., Radi, R., 2004, Trypanosoma brucei and Trypanosoma cruzi tryparedoxin peroxidases catalytically detoxify peroxynitrite via oxidation of fast reacting thiols. J. Biol. Chem. 279: 34175–34182.

    Article  PubMed  CAS  Google Scholar 

  • Ullu, E., Tschudi, C., Chakraborty, T., 2004, RNA interference in protozoan parasites. Cell. Microbiol. 6: 509–519.

    Article  PubMed  CAS  Google Scholar 

  • Vickers, T.J., Fairlamb, A.H., 2004, Trypanothione S-transferase activity in a trypanosomatid ribosomal elongation factor 1B. J. Biol. Chem. 279: 27246–27256.

    Article  PubMed  CAS  Google Scholar 

  • Vickers, T.J., Wyllie, S.H., Fairlamb, A.H., 2004a, Leishmania major elongation factor 1B complex has trypanothione S-transferase and peroxidase activity. J. Biol. Chem. 279: 49003–49009.

    Article  CAS  Google Scholar 

  • Vickers, T.J., Greig, N., Fairlamb, A.H., 2004b, A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in Leishmania major. Proc. Natl. Acad. Sci. USA 101: 13186–13191.

    Article  CAS  Google Scholar 

  • Vivancos, A.P., Castillo, E.A., Biteau, B., Nicot, C., Ayté, J., Toledano, M.B., Hidalgo, E., 2005, A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway. Proc. Natl. Acad. Sci. USA 102: 8875–8880.

    Article  PubMed  CAS  Google Scholar 

  • Walker, J., Acestor, N., Gongora, R., Quadroni, M., Segura, I., Fasel, N., Saravia, N.G., 2006, Comparative protein profiling identifies elongation factor-1beta and tryparedoxin peroxidase as factors associated with metastasis in Leishmania guyanensis. Mol. Biochem. Parasitol. 145: 254–264.

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson, S.R., Meyer, D.J., Kelly, J.M., 2000a, Biochemical characterization of a trypanosome enzyme with glutathione-dependent peroxidase activity. Biochem. J. 352: 755–761.

    Article  CAS  Google Scholar 

  • Wilkinson, S.R., Temperton, N.J., Mondragon, A., Kelly, J.M., 2000b, Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi. J. Biol. Chem. 275: 8220–8225.

    Article  CAS  Google Scholar 

  • Wilkinson, S.R., Meyer, D.J., Taylor, M.C., Bromley, E.V., Miles, M.A., Kelly, J.M., 2002a, 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.

    Article  CAS  Google Scholar 

  • Wilkinson, S.R., Obado, S.O., Mauricio, I.L., Kelly, J.M., 2002b, Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 99: 13453–13458.

    Article  CAS  Google Scholar 

  • Wilkinson, S.R., Taylor, M.C., Touitha, S., Mauricio, I.L., Meyer, D.J., Kelly, J.M., 2002c, TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum. Biochem. J. 364: 787–794.

    Article  CAS  Google Scholar 

  • Wilkinson, S.R., Horn, D., Prathalingam, S.R., Kelly, J.M., 2003, RNA interference identifies two hydroperoxide metabolizing enzymes that are essential to the bloodstream form of the african trypanosome. J. Biol. Chem. 278: 31640–31646.

    Article  PubMed  CAS  Google Scholar 

  • Wood, Z.A., Poole, L.B., Hantgan, R.R., Karplus, P.A., 2002, Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins. Biochemistry 41: 5493–5504.

    Article  PubMed  CAS  Google Scholar 

  • Wood, Z.A., Poole, L.B., Karplus, P.A., 2003, Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300: 650–653.

    Article  PubMed  CAS  Google Scholar 

  • Wyllie, S., Cunningham, M.L., Fairlamb, A.H., 2004, Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani. J. Biol. Chem. 279: 39925–39932.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 504, D-69120, Heidelberg, Germany

    Luise R. Krauth-Siegel, Marcelo A. Comini & Tanja Schlecker

Authors
  1. Luise R. Krauth-Siegel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcelo A. Comini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tanja Schlecker
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. MOLISA GmbH Magdeburg, Magdeburg, Germany

    Leopold Flohé

  2. University of Mainz, Mainz, Germany

    J. Robin Harris

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer

About this chapter

Cite this chapter

Krauth-Siegel, L.R., Comini, M.A., Schlecker, T. (2007). The Trypanothione System. In: Flohé, L., Harris, J.R. (eds) Peroxiredoxin Systems. Subcellular Biochemistry, vol 44. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6051-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation