Skip to main content
Log in

Translationally controlled tumor protein of Brugia malayi functions as an antioxidant protein

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Translationally controlled tumor protein (TCTP) is one of the most abundantly expressed proteins in the filarial parasites as well as in the other organisms. Several functions have been suggested for TCTP family of proteins ranging from calcium binding to histamine release function. However, its physiological function is still a mystery. Previous studies showed that the expression of TCTP is increased several-fold during oxidative stress. In the present work, we report the putative antioxidant function of Brugia malayi TCTP (BmTCTP). When tested in vitro, rBmTCTP could be reduced by a variety of reducing agents including thioredoxin. Such reduced form of rBmTCTP was able to protect DNA from oxidative damage, suggesting that BmTCTP may have an antioxidant function in the parasite. Sequence analysis of filarial TCTPs revealed that there are three cysteine amino acids located in the central portion of the protein. Subsequent targeted residue modification studies showed that these cysteine residues in rBmTCTP are critical for its antioxidant function. To determine the significance of this finding, rBmTCTP was overexpressed in vivo in Escherichia coli and subjected to oxidative stress. These studies showed that rBmTCTP significantly protected cells form oxidative damage. Taken together, these findings suggest that BmTCTP might be functioning as a non-classical antioxidant protein in the filarial parasites.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bhisutthibhan J, Pan XQ, Hossler PA, Walker DJ, Yowell CA, Carlton J, Dame JB, Meshnick SR (1998) The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin. J Biol Chem 273:16192–16198

    Article  PubMed  CAS  Google Scholar 

  • Bohm H, Benndorf R, Gaestel M, Gross B, Nurnberg P, Kraft R, Otto A, Bielka H (1989) The growth-related protein P23 of the Ehrlich ascites tumor: translational control, cloning and primary structure. Biochem Int 19:277–286

    PubMed  CAS  Google Scholar 

  • Bonnet C, Perret E, Dumont X, Picard A, Caput D, Lenaers G (2000) Identification and transcription control of fission yeast genes repressed by an ammonium starvation growth arrest. Yeast 16:23–33

    Article  PubMed  CAS  Google Scholar 

  • Cookson E, Blaxter ML, Selkirk ME (1992) Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase. Proc Natl Acad Sci USA 89:5837–5841

    Article  PubMed  CAS  Google Scholar 

  • Dabir P, Dabir S, Siva Prasad BV, Reddy MV (2006) Isolation and analysis of partial cDNA sequence coding for superoxide dismutase in Wuchereria bancrofti. Infect Genet Evol 6:287–291

    Article  PubMed  CAS  Google Scholar 

  • Efferth T (2006) Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr Drug Targets 7:407–421

    Article  PubMed  CAS  Google Scholar 

  • Gachet Y, Tournier S, Lee M, Lazaris-Karatzas A, Poulton T, Bommer UA (1999) The growth-related, translationally controlled protein P23 has properties of a tubulin binding protein and associates transiently with microtubules during the cell cycle. J Cell Sci 112(Pt 8):1257–1271

    PubMed  CAS  Google Scholar 

  • Ghosh I, Eisinger SW, Raghavan N, Scott AL (1998) Thioredoxin peroxidases from Brugia malayi. Mol Biochem Parasitol 91:207–220

    Article  PubMed  CAS  Google Scholar 

  • Gnanasekar M, Rao KV, Chen L, Narayanan RB, Geetha M, Scott AL, Ramaswamy K, Kaliraj P (2002) Molecular characterization of a calcium binding translationally controlled tumor protein homologue from the filarial parasites Brugia malayi and Wuchereria bancrofti. Mol Biochem Parasitol 121:107–118

    Article  PubMed  CAS  Google Scholar 

  • James ER, McLean DC Jr, Perler F (1994) Molecular cloning of an Onchocerca volvulus extracellular Cu–Zn superoxide dismutase. Infect Immun 62:713–716

    PubMed  CAS  Google Scholar 

  • Li F, Zhang D, Fujise K (2001) Characterization of fortilin, a novel antiapoptotic protein. J Biol Chem 276:47542–47549

    Article  PubMed  CAS  Google Scholar 

  • Li J, Zhang WB, Loukas A, Lin RY, Ito A, Zhang LH, Jones M, McManus DP (2004) Functional expression and characterization of Echinococcus granulosus thioredoxin peroxidase suggests a role in protection against oxidative damage. Gene 326:157–165

    Article  PubMed  CAS  Google Scholar 

  • Lim YS, Cha MK, Kim HK, Uhm TB, Park JW, Kim K, Kim IH (1993) Removals of hydrogen peroxide and hydroxyl radical by thiol-specific antioxidant protein as a possible role in vivo. Biochem Biophys Res Commun 192:273–280

    Article  PubMed  CAS  Google Scholar 

  • MacDonald SM, Bhisutthibhan J, Shapiro TA, Rogerson SJ, Taylor TE, Tembo M, Langdon JM, Meshnick SR (2001) Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo. Proc Natl Acad Sci USA 98:10829–10832

    Article  PubMed  CAS  Google Scholar 

  • Mak CH, Su KW, Ko RC (2001) Identification of some heat-induced genes of Trichinella spiralis. Parasitology 123:293–300

    Article  PubMed  CAS  Google Scholar 

  • Mak CH, Poon MW, Lun HM, Kwok PY, Ko RC (2007) Heat-inducible translationally controlled tumor protein of Trichinella pseudospiralis: cloning and regulation of gene expression. Parasitol Res 100:1105–1111

    Article  PubMed  CAS  Google Scholar 

  • Michael E, Bundy DA (1997) Global mapping of lymphatic filariasis. Parasitol Today 13:472–476

    Article  PubMed  CAS  Google Scholar 

  • Oikawa K, Ohbayashi T, Mimura J, Fujii-Kuriyama Y, Teshima S, Rokutan K, Mukai K, Kuroda M (2002) Dioxin stimulates synthesis and secretion of IgE-dependent histamine-releasing factor. Biochem Biophys Res Commun 290:984–987

    Article  PubMed  CAS  Google Scholar 

  • Rao UR, Salinas G, Mehta K, Klei TR (2000) Identification and localization of glutathione S-transferase as a potential target enzyme in Brugia species. Parasitol Res 86:908–915

    Article  PubMed  CAS  Google Scholar 

  • Rao KV, Chen L, Gnanasekar M, Ramaswamy K (2002) Cloning and characterization of a calcium-binding, histamine-releasing protein from Schistosoma mansoni. J Biol Chem 277:31207–31213

    Article  PubMed  CAS  Google Scholar 

  • Rathaur S, Fischer P, Domagalski M, Walter RD, Liebau E (2003) Brugia malayi and Wuchereria bancrofti: gene comparison and recombinant expression of pi-class related glutathione S-transferases. Exp Parasitol 103:177–181

    Article  PubMed  CAS  Google Scholar 

  • Redl B, Merschak P, Abt B, Wojnar P (1999) Phage display reveals a novel interaction of human tear lipocalin and thioredoxin which is relevant for ligand binding. FEBS Lett 460:182–186

    Article  PubMed  CAS  Google Scholar 

  • Rupec RA, Poujol D, Kaltschmidt C, Messer G (1998) Isolation of a hypoxia-induced cDNA with homology to the mammalian growth-related protein p23. Oncol Res 10:69–74

    PubMed  CAS  Google Scholar 

  • Sanchez JC, Schaller D, Ravier F, Golaz O, Jaccoud S, Belet M, Wilkins MR, James R, Deshusses J, Hochstrasser D (1997) Translationally controlled tumor protein: a protein identified in several nontumoral cells including erythrocytes. Electrophoresis 18:150–155

    Article  PubMed  CAS  Google Scholar 

  • Selkirk ME, Smith VP, Thomas GR, Gounaris K (1998) Resistance of filarial nematode parasites to oxidative stress. Int J Parasitol 28:1315–1332

    Article  PubMed  CAS  Google Scholar 

  • Sturzenbaum SR, Kille P, Morgan AJ (1998) Identification of heavy metal induced changes in the expression patterns of the translationally controlled tumour protein (TCTP) in the earthworm Lumbricus rubellus1. Biochim Biophys Acta 1398:294–304

    PubMed  CAS  Google Scholar 

  • Tuynder M, Susini L, Prieur S, Besse S, Fiucci G, Amson R, Telerman A (2002) Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1. Proc Natl Acad Sci USA 99:14976–14981

    Article  PubMed  CAS  Google Scholar 

  • Tuynder M, Fiucci G, Prieur S, Lespagnol A, Geant A, Beaucourt S, Duflaut D, Besse S, Susini L, Cavarelli J, Moras D, Amson R, Telerman A (2004) Translationally controlled tumor protein is a target of tumor reversion. Proc Natl Acad Sci USA 101:15364–15369

    Article  PubMed  CAS  Google Scholar 

  • Utzinger J, Xiao SH, Tanner M, Keiser J (2007) Artemisinins for schistosomiasis and beyond. Curr Opin Investig Drugs 8:105–116

    PubMed  CAS  Google Scholar 

  • Wang JH, Shan YJ, Cong YW, Wu LJ, Yuan XL, Zhao ZH, Wang SQ, Chen JP (2003) Identification of differentially expressed genes of acute hypoxia-treated HepG2 cells and hypoxia-acclimatized HepG2 cells. Sheng Li Xue Bao 55:324–330

    PubMed  CAS  Google Scholar 

  • Yarm FR (2002) Plk phosphorylation regulates the microtubule-stabilizing protein TCTP. Mol Cell Biol 22:6209–6221

    Article  PubMed  CAS  Google Scholar 

  • Yoneda K, Rokutan K, Nakamura Y, Yanagawa H, Kondo-Teshima S, Sone S (2004) Stimulation of human bronchial epithelial cells by IgE-dependent histamine-releasing factor. Am J Physiol Lung Cell Mol Physiol 286:L174–L181

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by a Public Health Service grants AI-39066 & AI-064745 from the NIAID. Experiments performed in this study comply with the current laws of USA.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kalyanasundaram Ramaswamy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gnanasekar, M., Ramaswamy, K. Translationally controlled tumor protein of Brugia malayi functions as an antioxidant protein. Parasitol Res 101, 1533–1540 (2007). https://doi.org/10.1007/s00436-007-0671-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-007-0671-z

Keywords

Navigation