Advertisement

BioMetals

, Volume 32, Issue 6, pp 887–899 | Cite as

Cadmium-dependent expression of a new metallothionein identified in Trichomonas vaginalis

  • Bryan Alexis Netzahualcoyotzi
  • Jonathan Puente-Rivera
  • Rodrigo Arreola
  • Julio César Torres Romero
  • Maximo Martínez Benitez
  • Rosalia Lira Carmona
  • Jorge Antonio Moreno Reyes
  • Jose de Jesús Olivares Trejo
  • María Elizbeth Alvarez SánchezEmail author
Article
  • 78 Downloads

Abstract

Metallothioneins (MTs) have been identified in a wide variety of organisms from bacteria to humans. The biological functions of these MTs have a key role in metalloregulatory metabolism and its expression is induced in response to different stimuli, particularly by divalent metal cations. Also, the action of MTs have been implicated in the survival of pathogens in presence of microbicidal concentration of divalent cations, which allows the establishment of the infection. Trichomonas vaginalis is a protozoan parasite that adapts to the microenvironment of the male urogenital tract, where cations such as zinc (Zn2+) and cadmium (Cd2+) are present. Nevertheless, the molecular mechanisms of metal tolerance and homeostasis is not yet dilucidated in this parasite. In this study, we have identified 4 potential MT-like sequences (tvmt´s) in T. vaginalis genome. Because tvmt-2, -3, and -4 corresponds to truncated partial genes, we characterized the trichomonad tvmt-1 gene. The bioinformatic analyses and the predicted protein (TvMT-1) show similar properties to the reported in other MTs. The expression patterns of tvmt-1 in the presence of several divalent cations (Fe2+, Mn2+, Zn2+ and Cd2+) were analyzed and we demonstrated that Cd2+ induce significantly their expression. By indirect immunofluorescence assays, we corroborated this positive regulation of TvMT-1 in the cytoplasm of parasites grown in the presence of Cd2+. The tvmt-1 promoter contains putative metal responsive elements, which are probably the responsible for the Cd2+-dependent expression of this gene. Our results suggest that tvmt-1 gene encode a metallothionein that may be responsible for the homeostatis and detoxification of Cd+2 in T. vaginalis.

Keywords

Trichomonas vaginalis Metallothionein Synthetic peptide Heavy metals 

Abbreviations

MT

Metallothioneins

TvMT

Metallothionein of Trichomonas vaginalis

Zn2+

Zinc

Cd2+

Cadmium

Cu2+

Copper

MTF-1

Metal transcription factor

MRE

Metal response element

Fe2+

Iron

Notes

Acknowledgements

This work was supported by UACM and a grant from CONACyT (83808) Mexico (to M.E.A.S.). JAMR was supported by a scholarship from CONACYT (296788). We acknowledge Ph.D.Vadim Pérez Koldenkova for their technical assistance with confocal microscopy at Laboratorio Nacional de Microscopía Avanzada/Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social. We appreciate the technical assistance of Laura Vazquez Carrillo and Alfredo Padilla-Barberi.

Compliance of ethical standards

Conflict of interest

The authors declare that they have no conflict of interest regarding the publication of this article.

Supplementary material

10534_2019_220_MOESM1_ESM.tif (65.4 mb)
Supplementary material 1 Fig. 1S Alignment of the MT1 and their homologues found in T. vaginalis. The proposed structural domains of the metal binding are repeated sequences. The N-terminal domains are different to others domains. Our predictions suggest that some domains (with 6-7 CYS) bind 2 divalent metals (Zn or Cd), other (with 9 CYS) 3 divalent metals and some (with 11 CYS) 4 divalent metal. Domains with 6-7 Cys can bind 2 metals, domains with 9 Cys can bind 3 metals and, domains with 11 Cys can bind 4 metals. The general consensus compared all repeated domains, the second consensus exclude the short domains (from XP_001321169.1: D5 and D7) and a Domain with modifications on the sequence from XP_001321197.1: D9). XP_001304130.1: TvMT-1 (TVAG_220940), XP_001584034.1: TvMT-2 (TVAG_182840), XP_001321169.1: TvMT-3 (TVAG_485930), XP_001321197.1: TvMT-4 (TVAG_486210) (TIFF 66979 kb)

References

  1. Andrews GK (2001) Cellular zinc sensors: MTF-1 regulation of gene expression. In: Maret W (ed) Zinc biochemistry, physiology, and homeostasis. Springer, Dordrecht, pp 37–51Google Scholar
  2. Atrian S, Capdevila M (2013) Metallothionein-protein interactions. Biomol Concepts 4:143–160PubMedGoogle Scholar
  3. Baird SK, Kurz T, Brunk UT (2006) Metallothionein protects against oxidative stress-induced lysosomal destabilization. Biochem J 394:275–283PubMedPubMedCentralGoogle Scholar
  4. Blindauer CA (2011) Bacterial metallothioneins: past, present, and questions for the future. J Biol Inorg Chem 16(7):1011PubMedGoogle Scholar
  5. Boldrin F, Santovito G, Formigari A, Bisharyan Y, Cassidy-Hanley D, Clark TG, Piccinni E (2008) MTT2, a copper-inducible metallothionein gene from Tetrahymena thermophila. Comp Biochem Physiol Part C 147:232–240Google Scholar
  6. Bremner I, Beattie J (1990) Metallothionein and the trace minerals. Annu Rev Nutr 10:63–83PubMedGoogle Scholar
  7. Carlton JM et al (2007) Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis. Science 315:207–212PubMedPubMedCentralGoogle Scholar
  8. Carpenè E, Andreani G, Isani G (2007) Metallothionein functions and structural characteristics. J Trace Elem Med Biol 21:35–39PubMedGoogle Scholar
  9. Corrêa AS, Andrade LR, Soares MJ (2002) Elemental composition of acidocalcisomes of Trypanosoma cruzi bloodstream trypomastigote forms. Parasitol Res 88:875–880PubMedGoogle Scholar
  10. Coyle P, Philcox J, Carey L, Rofe A (2002) Metallothionein: the multipurpose protein. Cell Mol Life Sci 59:627–647PubMedGoogle Scholar
  11. Fernández-Martín K, Alvarez-Sánchez M, Arana-Argáez V, Alvarez-Sánchez L, Lara-Riegos J, Torres-Romero J (2017) Genome-wide identification, in silico characterization and expression analysis of ZIP-like genes from Trichomonas vaginalis in response to zinc and iron. Biometals 30:663–675PubMedGoogle Scholar
  12. Figueroa-Angulo EE et al (2012) The effects of environmental factors on the virulence of Trichomonas vaginalis. Microbes Infect 14:1411–1427PubMedGoogle Scholar
  13. Francis MJ, Hastings GZ, Brown F, McDermed J, Lu YA, Tam JP (1991) Immunological evaluation of the multiple antigen peptide (MAP) system using the major immunogenic site of foot-and-mouth disease virus. Immunology 73:249–254PubMedPubMedCentralGoogle Scholar
  14. Gouy M, Guindon S, Gascuel O (2010) SeaView version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol Biol Evol 27(2):221–224PubMedGoogle Scholar
  15. Gui Z, Green AR, Kasrai M, Bancroft GM, Stillman MJ (1996) Sulfur K-edge EXAFS studies of cadmium-, zinc-, copper-, and silver-rabbit liver metallothioneins. Inorg Chem 35(22):6520–6529PubMedGoogle Scholar
  16. Hamer DH (1986) Metallothionein. Annu Rev Biochem 55:913–951PubMedGoogle Scholar
  17. Heuchel R, Radtke F, Georgiev O, Stark G, Aguet M, Schaffner W (1994) The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression. EMBO J 13:2870–2875PubMedPubMedCentralGoogle Scholar
  18. Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF (2007) Cadmium-induced cancers in animals and in humans. Int J Occupational and Environmental Health 13:202–212Google Scholar
  19. Isani G, Carpenè E (2014) Metallothioneins, unconventional proteins from unconventional animals: a long journey from nematodes to mammals. Biomolecules 4:435–457PubMedPubMedCentralGoogle Scholar
  20. Iuchi S (2001) Three classes of C2H2 zinc finger proteins. Cell Mol Life Sci 58:625–635PubMedGoogle Scholar
  21. Kimura T, Kambe T (2016) The functions of metallothionein and ZIP and ZnT transporters: an overview and perspective. Int J Mol Sci 17:336PubMedPubMedCentralGoogle Scholar
  22. Koizumi S, Gong P, Suzuki K, Murata M (2007) Cadmium-responsive element of the human heme oxygenase-1 gene mediates heat shock factor 1-dependent transcriptional activation. J Biol Chem 282(12):8715–8723PubMedGoogle Scholar
  23. Krieger JN, Rein MF (1982) Zinc sensitivity of Trichomonas vaginalis: in vitro studies and clinical implications. J Infect Dis 146:341–345PubMedGoogle Scholar
  24. Lachke SA, Srikantha T, Tsai LK, Daniels K, Soll DR (2000) Phenotypic switching in Candida glabrata involves phase-specific regulation of the Metallothionein gene MT-IIand the newly discovered hemolysin gene HLP. Infect Immun 68:884–895PubMedPubMedCentralGoogle Scholar
  25. Langmade SJ, Ravindra R, Daniels PJ, Andrews GK (2000) The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. J Biol Chem 275:34803–34809PubMedGoogle Scholar
  26. Leiva-Presa A, Capdevila M, Gonzalez-Duarte P (2004) Mercury (II) binding to metallothioneins: variables governing the formation and structural features of the mammalian Hg-MT species. Eur J Biochem 271(23–24):4872–4880PubMedGoogle Scholar
  27. M’kandawire E, Mierek-Adamska A, Stürzenbaum SR, Choongo K, Yabe J, Mwase M, Blindauer CA (2017) Metallothionein from wild populations of the African Catfish Clarias gariepinus: from sequence, protein expression and metal binding properties to transcriptional biomarker of metal pollution. Int J Mol Sci 18(7):1548–1575PubMedCentralGoogle Scholar
  28. Madico G, Quinn TC, Rompalo A, McKee KT, Gaydos CA (1998) Diagnosis of Trichomonas vaginalis infection by PCR using vaginal swab samples. J Clin Microbiol 36:3205–3210PubMedPubMedCentralGoogle Scholar
  29. Miles AT, Hawksworth GM, Beattie JH, Rodilla V (2000) Induction, regulation, degradation, and biological significance of mammalian metallothioneins. Crit Rev Biochem Mol Biol 35(1):35–70PubMedGoogle Scholar
  30. Nerland DE (2007) The antioxidant/electrophile response element motif. Drug Metab Rev 39(1):235–248PubMedGoogle Scholar
  31. Nordberg M (1998) Metallothioneins: historical review and state of knowledge. Talanta 46:243–254PubMedGoogle Scholar
  32. Nordberg M, Nordberg G (2000) Toxicological aspects of metallothionein. Cell Mol Biol (Noisy-le-Grand, France) 46:451–463Google Scholar
  33. Othman MS, Khonsue W, Kitana J, Thirakhupt K, Robson M, Borjan M, Kitana N (2012) Hepatic metallothionein and Glutathione-S-Transferase responses in two populations of rice frogs, Fejervarya limnocharis, naturally exposed to different environmental cadmium levels. Bull Environ Contam Toxicol 89:225–228PubMedPubMedCentralGoogle Scholar
  34. Pedrini-Martha V, Niederwanger M, Kopp R, Schnegg R, Dallinger R (2016) Physiological, diurnal and stress-related variability of cadmium-metallothionein gene expression in land snails. PLoS ONE 11:e0150442PubMedPubMedCentralGoogle Scholar
  35. Piccinni E, Staudenmann W, Albergoni V, De Gabrieli R, James P (1994) Purification and primary structure of metallothioneins induced by cadmium in the protists Tetrahymena pigmentosa and Tetrahymena pyriformis. Eur J Biochem 226(3):853–859PubMedGoogle Scholar
  36. Porcheron G, Garénaux A, Proulx J, Sabri M, Dozois CM (2013) Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence. Front Cell Infect Microbiol 3:90PubMedPubMedCentralGoogle Scholar
  37. Radtke F, Georgiev O, Müller H-P, Brugnera E, Schaffner W (1995) Functional domains of the heavy metal-responsive transcription regulator MTF-1. Nucleic Acids Res 23:2277–2286PubMedPubMedCentralGoogle Scholar
  38. Raghunath A, Sundarraj K, Nagarajan R, Arfuso F, Bian J, Kumar AP, Sethi G, Perumal E (2018) Antioxidant response elements: discovery, classes, regulation and potential applications. Redox Biol 17:297–314PubMedPubMedCentralGoogle Scholar
  39. Šimonytė S, Čerkašin G, Plančiūnienė R, Naginienė R, Ryselis S, Ivanov L (2003) Influence of cadmium and zinc on the mice resistance to Listeria monocytogenes infection. Medicina 39:767–772PubMedGoogle Scholar
  40. Sims HI, Chirn GW, Marr MT (2012) Single nucleotide in the MTF-1 binding site can determine metal-specific transcription activation. Proc Natl Acad Sci 109(41):16516–16521PubMedGoogle Scholar
  41. Skolarczyk J, Budzyński M, Pekar J, Małecka-Massalska T, Skórzyńska-Dziduszko K (2018) The impact of cadmium on male infertility. J Elementol 23:35Google Scholar
  42. Stankovic RK, Chung RS, Penkowa M (2007) Metallothioneins I and II: neuroprotective significance during CNS pathology. Int J Biochem Cell Biol 39(3):484–489PubMedGoogle Scholar
  43. Suzuki T, Takagi Y, Osanai H, Li L, Takeuchi M, Katoh Y, Kobayashi M, Yamamoto M (2005) Pi class glutathione S-transferase genes are regulated by Nrf 2 through an evolutionarily conserved regulatory element in zebrafish. Biochem J 388(Pt 1):65–73PubMedPubMedCentralGoogle Scholar
  44. Takahashi S (2012) Molecular functions of metallothionein and its role in hematological malignancies. J Hematol Oncol 5:41PubMedPubMedCentralGoogle Scholar
  45. Tucker SL, Thornton CR, Tasker K, Jacob C, Giles G, Egan M, Talbot NJ (2004) A fungal metallothionein is required for pathogenicity of Magnaporthe grisea. Plant Cell 16:1575–1588PubMedPubMedCentralGoogle Scholar
  46. Vašák M, Meloni G (2011) Chemistry and biology of mammalian metallothioneins. J Biol Inorg Chem 16(7):1067–1078PubMedGoogle Scholar
  47. Viarengo A, Burlando B, Ceratto N, Panfoli I (2000) Antioxidant role of metallothioneins: a comparative overview. Cell Mol Biol 46(2):407–417PubMedGoogle Scholar
  48. Villalpando JL et al (2017) TvZNF1 is a C 2 H 2 zinc finger protein of Trichomonas vaginalis. Biometals 30(6):861–872PubMedGoogle Scholar
  49. Waalkes MP, Anver MR, Diwan BA (1999) Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes. J Toxicol Environ Health Part A 58:199–214PubMedGoogle Scholar
  50. Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192:95–117PubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Bryan Alexis Netzahualcoyotzi
    • 1
  • Jonathan Puente-Rivera
    • 1
  • Rodrigo Arreola
    • 2
  • Julio César Torres Romero
    • 3
  • Maximo Martínez Benitez
    • 1
  • Rosalia Lira Carmona
    • 4
  • Jorge Antonio Moreno Reyes
    • 1
  • Jose de Jesús Olivares Trejo
    • 1
  • María Elizbeth Alvarez Sánchez
    • 1
    Email author
  1. 1.Posgrado en Ciencias GenómicasUniversidad Autónoma de la Ciudad de México (UACM)Mexico CityMexico
  2. 2.Psychiatric Genetics Department, Clinical Research BranchNational Institute of PsychiatryMexico CityMexico
  3. 3.Laboratorio de Bioquímica y Genética MolecularFacultad de Química de la Universidad Autónoma de YucatánMéridaMexico
  4. 4.Unidad de Investigacion Medica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatria, Centro Medico Nacional “Siglo XXI”Instituto Mexicano del Seguro Social (IMSS)Mexico CityMexico

Personalised recommendations