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Life and death of Trypanosoma cruzi in presence of metals

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Abstract

Trypanosoma cruzi has many molecules that need metallic elements to work, allowing cell invasion and the establishment of infection, causing Chagas disease. Nonetheless, knowledge regarding how the parasites address metals and maintain homeostasis is lacking. To study this relationship, zinc, cadmium and mercury were chosen. Epimastigote, trypomastigote and intracellular forms of T. cruzi were incubated with these metals for different times and at different concentrations. In general, epimastigotes were the most sensitive and trypomastigotes the most resistant to metals. ZnCl2 induced low toxic effects to all parasite forms. Although the parasites were very sensitive to the toxic effects of CdCl2 and HgCl2, pretreatment with ZnCl2 decreased the death rate. The trypomastigotes pretreated with CdCl2 were unable to infect the host cells, and the treated intracellular forms were damaged after 2 h of incubation, when the toxic effects were poorly reverted. New insights on metal toxicity mechanisms are provided, helping to understand how metallic ions influence the parasite’s biochemical and physiological processes.

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References

  • Alvarez VE, Niemirowicz GT, Cazzulo JJ (2012) The peptidases of Trypanosoma cruzi: digestive enzymes, virulence factors, and mediators of autophagy and programmed cell death. Biochim Biophys Acta 1824:195–206

    Article  CAS  PubMed  Google Scholar 

  • Alves MJ, Colli W (2007) Trypanosoma cruzi: adhesion to the host cell and intracellular survival. IUBMB Life 59:274–279

    Article  CAS  PubMed  Google Scholar 

  • Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM (2008) Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem 13:1205–1218

    Article  CAS  PubMed  Google Scholar 

  • Beraldo H, Gambino D (2004) The wide pharmacological versatility of semicarbazones, thiosemicarbazones and their metal complexes. Mini Rev Med Chem 4:31–39

    Article  CAS  PubMed  Google Scholar 

  • Bray TM, Bettger WJ (1990) The physiological role of zinc as an antioxidant. Free Radic Biol Med 8:281–291

    Article  CAS  PubMed  Google Scholar 

  • Butcher H, Kennette W, Collins O et al (2003) A sensitive time-resolved fluorescent immunoassay for metallothionein protein. J Immunol Methods 272:247–256

    Article  CAS  PubMed  Google Scholar 

  • Carvalho LP, Melo EJT (2016) Non-essential and essential metal effects on intracellular Toxoplasma gondii. Eur J Biomed Pharm Sci 3:23–32

    Google Scholar 

  • Carvalho CS, Melo EJT, Tenório RP, Góes AJ (2010) Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives. Braz J Med Biol Res 43:139–149

    Article  CAS  PubMed  Google Scholar 

  • Demoro B, Caruso F, Rossi M et al (2010) Risedronate metal complexes potentially active against Chagas disease. J Inorg Biochem 104:1252–1258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Demoro B, Almeida RFM, Marques F et al (2013) Screening organometallic binuclear thiosemicarbazone ruthenium complexes as potential anti-tumour agents: cytotoxic activity and human serum albumin binding mechanism. Dalton Trans 42:7131–7146

    Article  CAS  PubMed  Google Scholar 

  • Eide DJ (2006) Zinc transporters and the cellular trafficking of zinc. Biochim Biophys Acta 1763:711–722

    Article  CAS  PubMed  Google Scholar 

  • Eptin CL, Coatesa BM, Engman DM (2010) Molecular mechanisms of host cell invasion by Trypanosoma cruzi. Exp Parasitol 126:283–291

    Article  Google Scholar 

  • Fairlamb AH, Cerami A (1992) Metabolism and fuctions of trypanothione in the Kinetoplastida. Annu Rev Microbiol 46:695–729

    Article  CAS  PubMed  Google Scholar 

  • Feng W, Cai J, Pierce WM et al (2005) Metallothionein transfers zinc to mitochondrial aconitase through a direct interaction in mouse hearts. Biochem Biophys Res Commun 332:853–858

    Article  CAS  PubMed  Google Scholar 

  • Fernández M, Varela J, Correia I et al (2013) A new series of heteroleptic oxidovanadium (IV) compounds with phenanthroline-derived co-ligands: selective Trypanosoma cruzi growth inhibitors. Dalton Trans 42:11900–11911

    Article  PubMed  Google Scholar 

  • Ferreira RC, Kessier RL, Lorenzo MG et al (2016) Colonization of Rhodnius prolixus gut by Trypanosoma cruzi involves an extensive parasite killing. Parasitology 143:434–443

    Article  PubMed  Google Scholar 

  • Florencio-Martínez L, Márquez-Dueñas C, Ballesteros-Rodea G, Martínez-Calvillo S, Manning-Cela R (2010) Cellular analysis of host cell infection by different developmental stages of Trypanosoma cruzi. Exp Parasitol 126:332–336

    Article  PubMed  Google Scholar 

  • Formigari A, Irato P, Santon A (2007) Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects. Comp Biochem Physiol C 146:443–459

    Google Scholar 

  • Girault L, Boudou A, Drfourc EJ (1997) Methyl mercury interactions with phospholipid membranes as reported by fluorescence, 31P and 199Hg NMR. Biochim Biophys Acta 1325:250–262

    Article  CAS  PubMed  Google Scholar 

  • Gomes MAGB, Carvalho LP, Melo EJT, Oliveira RR, Maria EJ (2012) Evaluating anti-Toxoplasma gondii activity of new serie of phenylsemicarbazone and phenylthiosemicarbazones in vitro. Med Chem Res 22:3574–3580

    Article  Google Scholar 

  • Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87

    Article  CAS  PubMed  Google Scholar 

  • Klaassen CD, Liu J, Choudhuri S (1999) Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol 39:267–294

    Article  CAS  PubMed  Google Scholar 

  • Kollien AH, Schaub GA (2000) The development of Trypanosoma cruzi in triatominae. Parasitol Today 16:381–387

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni MM, Olson CL, Engman DM, McGwire BS (2009) Trypanosoma cruzi GP63 proteins undergo stage-specific differential posttranslational modification and are important for host cell infection. Infec Immu 77:2193–2200

    Article  CAS  Google Scholar 

  • Lemire JA, Harrison JJ, Turner RJ (2013) Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 11:371–384

    Article  CAS  PubMed  Google Scholar 

  • Ley V, Robbins ES, Nussenzweig V, Andrews NW (1990) The exit of Trypanosoma cruzi from the phagosome is inhibiteed by raising the pH of acidic compartments. J Exp Med 171:401–413

    Article  CAS  PubMed  Google Scholar 

  • Maret W, Vallee BL (1998) Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc Natl Acad Sci USA 95:3478–3482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez-Finley EJ, Chakraborty S, Fretham SJ, Aschner M (2012) Cellular transport and homeostasis of essential and nonessential metals. Metallomics 4:593–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maya JD, Rodríguez A, Pino L et al (2004) Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi. Biol Res 37:61–69

    Article  CAS  PubMed  Google Scholar 

  • Morey JR, McDevitt CA, Kehl-Fie TE (2015) Host-imposed manganese starvation of invading pathogens: two routes to the same destination. Biometals 28:509–519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moulis JM (2010) Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals. Biometals 23:877–896

    Article  CAS  PubMed  Google Scholar 

  • Moulis JM, Thévenod F (2010) New perspectives in cadmium toxicity: an introduction. Biometals 23:763–768

    Article  CAS  PubMed  Google Scholar 

  • Nogueira NP, Saraiva FMS, Sultano PE (2015) Proliferation and differentiation of Trypanosoma cruzi inside its vector have a new trigger: redox status. PLoS ONE 10:1–16

    Google Scholar 

  • Parkin G (2004) Synthetic analogues relevant to the structure and function of zinc enzymes. Chem Rev 104:699–768

    Article  CAS  PubMed  Google Scholar 

  • Rana SV (2008) Metals and apoptosis: recent developments. J Trace Elem Med Biol 22:262–284

    Article  CAS  PubMed  Google Scholar 

  • Reyes-Caballero H, Campanello GC, Giedroc DP (2011) Metalloregulatory proteins: metal selectivity and allosteric switching. Biophys Chem 156:103–114

    Article  CAS  PubMed  Google Scholar 

  • Roohani N, Hurrell R, Kelishadi R, Schulin R (2013) Zinc and its importance for human health: an integrative review. J Res Med Sci 18:144–157

    PubMed  PubMed Central  Google Scholar 

  • Rosestolato CT, Dutra JM, Souza W, Carvalho TM (2002) Participation of host cell actin filaments during interaction of trypomastigote forms of Trypanosoma cruzi with host cells. Cell Struct Funct 27:91–98

    Article  CAS  PubMed  Google Scholar 

  • Rousselet E, Richaud P, Douki T et al (2008) A zinc-resistant human epithelial cell line is impaired in cadmium and manganese import. Toxicol Appl Pharmacol 230:312–319

    Article  CAS  PubMed  Google Scholar 

  • Sánchez-Delgado RA, Anzellotti A (2004) Metal complexes as chemotherapeutic agents against tropical diseases: trypanosomiasis, malaria and leishmaniasis. Mini Rev Med Chem 4:23–30

    Article  PubMed  Google Scholar 

  • Santon A, Albergoni V, Sturniolo GC, Irato P (2004) Evaluation of MT expression and detection of apoptotic cells in LEC rat kidneys. Biochim Biophys Acta 1688:223–231

    Article  CAS  PubMed  Google Scholar 

  • Santos KK, Matias EF, Tintino SR et al (2012) Anti-Trypanosoma cruzi and cytotoxic activities of Eugenia uniflora L. Exp Parasitol 131:130–132

    Article  PubMed  Google Scholar 

  • Sears ME (2013) Chelation: harnessing and enhancing heavy metal detoxification—a review. Sci World J 2013:219840

    Article  Google Scholar 

  • Shimoda R, Achanzar WE, Qu W et al (2003) Metallothionein is a potential negative regulator of apoptosis. Toxicol Sci 73:294–300

    Article  CAS  PubMed  Google Scholar 

  • Souza W (2002) From the cell biology to the development of new chemotherapeutic approaches against trypanosomatids: dreams and reality. Kinetoplastid Biol Dis 1:1–21

    Article  Google Scholar 

  • Souza W, Carvalho TM, Barrias ES (2010) Review on Trypanosoma cruzi: host cell interaction. Int J Cell Biol 2010:295493

    Article  Google Scholar 

  • Suhy DA, Simon KD, Linzer DI, O’Halloran TV (1999) Metallothionein is part of a zinc-scavenging mechanism for cell survival under conditions of extreme zinc deprivation. J Biol Chem 274:9183–9192

    Article  CAS  PubMed  Google Scholar 

  • Templeton DM, Liu Y (2010) Chemico-biological interactions multiple roles of cadmium in cell death and survival. Chem Biol Interact 188:267–275

    Article  CAS  PubMed  Google Scholar 

  • Tyler KM, Engman DM (2001) The life cycle of Trypanosoma cruzi revisited. Int J Parasitol 31(5–6):472–481

    Article  CAS  PubMed  Google Scholar 

  • Valko M, Rhodes CJ, Moncol J et al (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    Article  CAS  PubMed  Google Scholar 

  • Vašák M (2005) Advances in metallothionein structure and functions. J Trace Elem Med Biol 19:13–17

    Article  PubMed  Google Scholar 

  • Villalta F, Scharfstein J, Ashton AW et al (2009) Perspectives on the Trypanosoma cruzi-host cell receptor interactions. Parasitol Res 104:1251–1260

    Article  PubMed  PubMed Central  Google Scholar 

  • Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192:95–117

    Article  CAS  PubMed  Google Scholar 

  • Waldron K, Rutherford JC, Ford D, Robinson NJ (2009) Metalloproteins and metal sensing. Nature 460:823–830

    Article  CAS  PubMed  Google Scholar 

  • Weinberg ED (1966) Roles of metallic ions in host-parasite interactions differential metallic ion growth requirements of virulent and avirulent bacterial strains. Microbiol Mol Biol Rev 30:136–151

    CAS  Google Scholar 

  • Wilkinson SR, Taylor MC, Touitha S (2002) 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  PubMed  PubMed Central  Google Scholar 

  • Yoshida M, Saegusa Y, Fukuda A (2005) Measurement of radical-scavenging ability in hepatic metallothionein of rat using in vivo electron spin resonance spectroscopy. Toxicology 213:74–80

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

FAPERJ (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro) (Grant number: E-26/010.002612/2014) and CNPq (Conselho Nacional de Pesquisa).

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  1. Laboratory of Tissue and Cell Biology, State University of North Fluminense – Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro, 28013-602, Brazil

    Laís Pessanha de Carvalho & Edésio José Tenório de Melo

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  1. Laís Pessanha de Carvalho
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Correspondence to Edésio José Tenório de Melo.

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de Carvalho, L.P., de Melo, E.J.T. Life and death of Trypanosoma cruzi in presence of metals. Biometals 30, 955–974 (2017). https://doi.org/10.1007/s10534-017-0064-4

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