Biological Trace Element Research

, Volume 155, Issue 2, pp 261–266 | Cite as

Phenylethynyl-Butyltellurium Inhibits the Sulfhydryl Enzyme Na+, K+-ATPase: An Effect Dependent on the Tellurium Atom

  • Caroline B. Quines
  • Suzan G. Rosa
  • José S. S. Neto
  • Gilson Zeni
  • Cristina W. NogueiraEmail author


Organotellurium compounds are known for their toxicological effects. These effects may be associated with the chemical structure of these compounds and the oxidation state of the tellurium atom. In this context, 2-phenylethynyl-butyltellurium (PEBT) inhibits the activity of the sulfhydryl enzyme, δ-aminolevulinate dehydratase. The present study investigated on the importance of the tellurium atom in the PEBT ability to oxidize mono- and dithiols of low molecular weight and sulfhydryl enzymes in vitro. PEBT, at high micromolar concentrations, oxidized dithiothreitol (DTT) and inhibited cerebral Na+, K+-ATPase activity, but did not alter the lactate dehydrogenase activity. The inhibition of cerebral Na+, K+-ATPase activity was completely restored by DTT. By contrast, 2-phenylethynyl-butyl, a molecule without the tellurium atom, neither oxidized DTT nor altered the Na+, K+-ATPase activity. In conclusion, the tellurium atom of PEBT is crucial for the catalytic oxidation of sulfhydryl groups from thiols of low molecular weight and from Na+, K+-ATPase.


Tellurium Sulfhydryl enzymes Thiol Toxicity Na+, K+-ATPase 



The financial support by UFSM, CAPES, FAPERGS/CNPq (PRONEX) (research grant no. 10/0005-1) and FAPERGS (no. 10/0711-6) is gratefully acknowledged. C.W.N is a recipient of CNPq fellowship.


  1. 1.
    Ba LA, Doring M, Jamier V, Jacob C (2010) Tellurium: an element with great biological potency and potential. Org Biomol Chem 8:4203–4216PubMedCrossRefGoogle Scholar
  2. 2.
    Petragnani N (1995) In: Comprehensive organometallic chemistry II (Ed. A. Mckillop), vol. LI, Pergamon, Exeter.Google Scholar
  3. 3.
    Degrandi TH, Oliveira IM, Almeida GS, Garcia CRL, Villela IV, Guecheva TN, Rosa RM, Henriques JAP (2010) Evaluation of the cytotoxicity, genotoxicity and mutagenicity of diphenyl ditelluride in several biological models. Mutagenesis 25:257–269PubMedCrossRefGoogle Scholar
  4. 4.
    Roy S, Hardej D (2011) Tellurium tetrachloride and diphenyl ditelluride cause cytotoxicity in rat hippocampal astrocytes. Food Chem Toxicol 49:2564–2574PubMedCrossRefGoogle Scholar
  5. 5.
    Comparsi B, Meinerz DF, Franco JL, Posser T, Prestes AS, Stefanello ST, Santos DB, Wagner C, Farina M, Aschner M, Dafre AL, Rocha JBT (2012) Diphenyl ditelluride targets brain selenoproteins in vivo: inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure. Mol Cell Biochem 370:173–182PubMedCrossRefGoogle Scholar
  6. 6.
    Heimfarth LL, Samanta O, Reis KP, Lima BO, Zamboni F, Lacerda S, Soska AK, Wild L, Rocha JBT, Pessoa-Pureur R (2012) Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats. Arch Toxicol 86:217–230PubMedCrossRefGoogle Scholar
  7. 7.
    Nogueira CW, Zeni G, Rocha JBT (2004) Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev 104:6255–6285PubMedCrossRefGoogle Scholar
  8. 8.
    Brüning CA, Prigol M, Barancelli DA, Nogueira CW, Zeni G (2009) Disubstituted diaryl diselenides inhibit d-ALA-D and Na+, K+-ATPase activities in rat brain homogenates in vitro. Mol Cell Biochem 332:17–24PubMedCrossRefGoogle Scholar
  9. 9.
    Nogueira CW, Rocha JBT (2012) The chemistry of organic selenium and tellurium compounds. In: Rappport Z (ed) Patai’s chemistry of functional groups. Wiley, New York, pp 1277–1357Google Scholar
  10. 10.
    Souza ACG, Luchese C, Neto José SS, Nogueira CW (2008) Antioxidant effect of a novel class of telluroacetilene compounds: studies in vitro and in vivo. Life Sci 84:351–357CrossRefGoogle Scholar
  11. 11.
    Souza ACG, Acker CI, Gay BM, Neto JSS, Nogueira CW (2012) 2-Phenylethynyl-butyltellurium improves memory in mice. Neurochem Int 60:409–414PubMedCrossRefGoogle Scholar
  12. 12.
    Souza ACG, Sari MHM, Pinton S, Luchese C, Neto JSS, Nogueira CW (2013) 2-Phenylethynyl-butyltellurium attenuates amyloid-β peptide(25–35)-induced learning and memory impairments in Mice. J Neurosci Res. doi: 10.1002/jnr.23211 Google Scholar
  13. 13.
    Comasseto JV, Menezes PH, Stefani HA, Zeni G, Braga AL (1996) Addition of hydrogen halides to acetylenic selenides. Synthesis of 1-halo-1-selenoalkenes. Tetrahedron 52:9687–9702CrossRefGoogle Scholar
  14. 14.
    Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77PubMedCrossRefGoogle Scholar
  15. 15.
    Fiske CH, Subbarows YJ (1925) The calorimetric determination of phosphorus. Biol Chem 66:375–381Google Scholar
  16. 16.
    Pereira ME, Borignon AM, Burger C (1991) Long-term treatment with 2,5-hexaedione has no effect on the specific activity of some brain and liver glycolytic enzymes of adults rats. Bras J Med Biol 24:735–740Google Scholar
  17. 17.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  18. 18.
    Reinhard L, Tidow H, Clausen MJ, Nissen P (2013) Na+, K+-ATPase as a docking station: protein–protein complexes of the Na+, K+-ATPase. Cell Mol Life Sci 70:205–222PubMedCrossRefGoogle Scholar
  19. 19.
    Zhanga L, Suna Y, Panb S, Lic J, Qud Y, Lia Y, Wangc Y, Gaoa Z (2013) Na+−K+-ATPase, a potent neuroprotective modulator against Alzheimer disease. Fund Clin Pharmacol 27:96–103CrossRefGoogle Scholar
  20. 20.
    Moseley AE, Williams MT, Schaefer TL, Bohanan CS, Neumann JC, Behbehani MM et al (2007) Deficiency in Na, K-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice. J Neurosci 27:616–626PubMedCrossRefGoogle Scholar
  21. 21.
    Carfagna MA, Ponsler GD, Muhoberac BB (1996) Inhibition of ATPase activity in rat synaptic plasma membranes by simultaneous exposure to metals. Chem Biol Interact 100:53–65. doi: 10.1016/0009-2797(95)03685-7 PubMedCrossRefGoogle Scholar
  22. 22.
    da Rocha JT, Pinton S, Gai BM, Nogueira CW (2013) Diphenyl diselenide reduces mechanical and thermal nociceptive behavioral responses after unilateral intrastriatal administration of 6-hydroxydopamine in rats. Biol Trace Elem Res. doi: 10.1007/s12011-013-9736-2 PubMedGoogle Scholar
  23. 23.
    Cunha LOR, Urano ME, Chagas JR, Almeida PC, Bincoletto C, Tersariol ILS, Comasseto JV (2005) Tellurium-based cysteine protease inhibitors: evaluation of novel organotellurium (IV) compounds as inhibitors of human cathepsin B. Biorg Med Chem Lett 15:755–760CrossRefGoogle Scholar
  24. 24.
    Vinals C, de Bolle X, Depiereux E, Feytmans E (1995) Knowledge-based modeling of the D-lactate dehydrogenase three-dimensional structure. Proteins 21:307–318PubMedCrossRefGoogle Scholar
  25. 25.
    Ward RA, Brassington C, Breeze AL, Caputo A, Critchlow S, Davies G, Goodwin L, Hassall G, Greenwood R, Holdgate GA, Mrosek M, Norman RA, Pearson S, Tart J, Tucker JA, Vogtherr M, David W, Jonathan W, Jon W, Kevin H (2012) Design and synthesis of novel lactate dehydrogenase a inhibitors by fragment-based lead generation. J Med Chem 55:3285–3306PubMedCrossRefGoogle Scholar
  26. 26.
    Phillips D, Blake CCF, Watson HC (1981) The enzymes of glycolysis: structure, activity, and evolution. Philos Trans R Soc Lond B Biol Sci 293:1–214Google Scholar
  27. 27.
    Abad-Zapatero C, Griffith JP, Sussman JL, Rossman MG (1987) Refined crystal structure of dogfish M4 apo-lactate dehydrogenase. J Mol Biol 198:445–467PubMedCrossRefGoogle Scholar
  28. 28.
    Taylor SS, Oxley SS (1976) Homologies in the active site regions of lactate dehydrogenases. Arch Biochem Biophys 175:373–383PubMedCrossRefGoogle Scholar
  29. 29.
    Breccia JD, Andersson MM, Hatti-Kaul R (2002) The role of poly (ethyleneimine) in stabilization against metal-catalyzed oxidation of proteins: a case study with lactate dehydrogenase. Biochim Biophys Acta 1570:165–173PubMedCrossRefGoogle Scholar
  30. 30.
    Lugokenski TH, Müller LG, Taube PS, Rocha JBT, Pereira ME (2010) Inhibitory effect of ebselen on lactate dehydrogenase activity from mammals: a comparative study with diphenyl diselenide and diphenyl ditelluride. Drug Chem Toxicol 34(1):66–76PubMedCrossRefGoogle Scholar
  31. 31.
    Barbosa NBV, Rocha JBT, Zeni G, Emanuelli T, Beque MC, Braga AL (1998) Effect of organic forms of selenium on d-aminolevulinate dehydratase from liver, kidney, and brain of adult rats. Toxicol Appl Pharm 149:243–253CrossRefGoogle Scholar
  32. 32.
    Borges VC, Rocha JB, Nogueira CW (2005) Effect of diphenyl diselenide, dipheyl ditelluride and ebselen on cerebral Na+, K+-ATPase activity in rats. Toxicology 215:191–197PubMedCrossRefGoogle Scholar
  33. 33.
    Savegnago L, Borges VC, Alves D, Jess CR, Rocha JBT, Nogueira CW (2006) Evaluation of antioxidant activity and potential toxicity of 1-buthyltelurenyl-2-methylthioheptene. Life Sci 79:1546–1552PubMedCrossRefGoogle Scholar
  34. 34.
    Ávila DS, Palma AS, Colle D, Scolari R, Manarin F, Silveira AF, Nogueira CW, Rocha JBT, Soares FAA (2011) Hepatoprotective activity of a vinylic telluride against acute exposure to acetaminophen. Eur J Pharmacol 661:92–101PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Caroline B. Quines
    • 1
  • Suzan G. Rosa
    • 1
  • José S. S. Neto
    • 1
  • Gilson Zeni
    • 1
  • Cristina W. Nogueira
    • 1
    • 2
    Email author
  1. 1.Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa MariaSanta Maria, CEPBrazil
  2. 2.Departamento de Química, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa MariaSanta MariaBrazil

Personalised recommendations