Advertisement

Neurochemical Research

, Volume 32, Issue 6, pp 953–958 | Cite as

Heavy Metals Modulate Glutamatergic System in Human Platelets

  • V. C. Borges
  • F. W. Santos
  • J. B. T. Rocha
  • C. W. Nogueira
Original Paper

Abstract

Research strategies have been developed to characterize parameters in peripheral tissues that might easily be measured in humans as surrogate markers of damage, dysfunction or interactions involving neural targets of toxicants. The similarities between platelet and neuron may even be clinically important, as a number of biochemical markers show parallel changes in the central nervous system (CNS) and platelets. The purpose of our research was to investigate the effect of Hg2+, Pb2+ and Cd2+ on the [3H]-glutamate binding and [3H]-glutamate uptake in human platelets. The involvement of oxidative stress in the modulation of glutamatergic system induced by heavy metals was also investigated. The present study clearly demonstrates that Hg2+, Cd2+, and Pb2+ inhibited [3H]-glutamate uptake in human platelets. Hg2+ inhibited [3H]-glutamate binding, while Cd2+ and Pb2+ stimulated [3H]-glutamate binding in human platelets. Hg2+, Cd2+ and Pb2+ increased lipid peroxidation levels and reactive oxygen species (ROS) measurement in platelets. The present limited results could suggest that glutamatergic system may be used as a potential biomarker for neurotoxic action of heavy metals in humans.

Keywords

Platelets Heavy metals Glutamate binding Glutamate uptake SNC 

Notes

Acknowledgments

The financial support by UFSM, FAPERGS, CAPES, and CNPq is gratefully acknowledged. J.B.T.R, C.W.N., and F.W.S. are the recipients of CNPq fellowships.

References

  1. 1.
    Schoepp DD, Con PJ (1993) Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol Sci 14:13–20PubMedCrossRefGoogle Scholar
  2. 2.
    Aschner M, Fitsanakis V (2005) The importance of glutamate, glycine, and aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicity. Toxicol Appl Pharmacol 204:343–354PubMedCrossRefGoogle Scholar
  3. 3.
    Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105PubMedCrossRefGoogle Scholar
  4. 4.
    Rothstein JD, Van Kammen M, Martin L, Levey AL, Kuncl RW (1995) Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38:73–84PubMedCrossRefGoogle Scholar
  5. 5.
    Rossi DJ, Oshima T, Attwell D (2000) Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403:316–321PubMedCrossRefGoogle Scholar
  6. 6.
    Proper EA, Hoogland G, Kappen SM, Jansen GH, Rensen MG, Schrama LH (2002) Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. Brain 125:32–43PubMedCrossRefGoogle Scholar
  7. 7.
    Manzo L, Castoldi AF, Coccini T, Rossi AD, Nicotera P, Costa LG (1995) Mechanisms of neurotoxicity: applications to human biomonitoring. Toxicol Lett 77:63–72PubMedCrossRefGoogle Scholar
  8. 8.
    De Gaetano G, Garattino S (1978) Platelets: a multidisciplinary approach. Raven Press, New YorkGoogle Scholar
  9. 9.
    Mangano RM, Schwarcz R (1981) Platelet glutamate and aspartate uptake in Hungtington’s disease. J Neurochem 37:1072–1074PubMedCrossRefGoogle Scholar
  10. 10.
    Zoia C, Cogliati T, Tagliabue E, Cavaletti G, Sala G, Galimberti G, Rivolta L, Rossi V, Frattola L, Ferrarese C (2004) Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer’s disease. Neurobiol Aging 25:149–157PubMedCrossRefGoogle Scholar
  11. 11.
    Hoogland G, Bos IWM, Kupper F, Spierenburg HA, van Nieuwenhuizen O, de Graan PNE (2005) Thrombin-stimulated glutamate uptake in human platelets is predominantly mediated by the glial glutamate transporter EAAT2. Neurochem Int 47:499–506PubMedCrossRefGoogle Scholar
  12. 12.
    Ferrarese C, Zoia C, Pecora N, Piolti R, Frigo M, Bianchi G, Sala G, Begni B, Riva R, Frattola L (1999) Reduced platelet glutamate uptake in Parkinson’s disease. J Neural Transm 106:685–692PubMedCrossRefGoogle Scholar
  13. 13.
    Ferrarese C, Begni B, Canevari C, Zoia C, Piolti R, Frigo M, Appollonio L, Frattola L, Mangano RM, Schwarcz R (2000) Glutamate uptake is decreased in platelets from Alzheimer’s disease patients. Ann Neurol 47:641–643PubMedCrossRefGoogle Scholar
  14. 14.
    Ferrarese C, Sala G, Riva R, Begni B, Zoia C, Tremolizzo L, Galimberti G, Milul A, Bastone A, Mennini T, Balzarini C, Frattola L, Beghi E (2001) Decreased platelet glutamate uptake in patients with amyotrophic lateral sclerosis. Neurology 56:270–272PubMedGoogle Scholar
  15. 15.
    Nascimento CAM, Nogueira CW, Borges VC, Rocha JBT (2006) Changes in [3H]-glutamate uptake into platelets from patients with bipolar I disorder. Psychiatry Res 141:343–347PubMedCrossRefGoogle Scholar
  16. 16.
    Page AL, Al-Amamy MM, Chang AC (1986) Cadmium in the environment and its entry into terrestrial food chain crops. In: Foulkes EC (ed.) Cadmium. Springer, Berlin Heidelberg, New York, pp 33–74Google Scholar
  17. 17.
    Goering PL, Waalkes MP, Klaassen CD (1995) Toxicology of cadmium. In: Goyer RA, Cherian MG (eds) Handbook of experimental toxicology, vol 115. Springer, Berlin Heidelberg New York, pp 189–213Google Scholar
  18. 18.
    Minami A, Takeda A, Nishibaba D, Takefuta S, Oku N (2001) Cadmium toxicity in synaptic neurotransmission in the brain. Brain Res 894:336–339PubMedCrossRefGoogle Scholar
  19. 19.
    Shukla GS, Singhal RL (1984) The present status of biological effects of toxic metals in the environment: lead, cadmium and manganese. Can J Physiol Pharmacol 62:1015–1031PubMedGoogle Scholar
  20. 20.
    Wong PCL, Lai JCK, Davinson AN (1981) Selective-inhibition of l-glutamate and gammaaminobutyrate transport in nerve ending particles by aluminum, manganese, and cadmium chloride. J Inor Biochem 14:253–260CrossRefGoogle Scholar
  21. 21.
    Aschner M, Yao CP, Allen JW, Tan KW (2000) Methylmercury alters glutamate transport in astrocytes. Neurochem Int 37:199–206PubMedCrossRefGoogle Scholar
  22. 22.
    Atchison WD, Hare MF (1994) Mechanisms of methylmercury-induced neurotoxicity. FASEB J 8:622–629PubMedGoogle Scholar
  23. 23.
    Yamashita T, Ando Y, Sakashita N, Hirayama K, Tanaka Y, Tashima K, Uchino M, Ando M (1997) Role of nitric oxide in the cerebellar degeneration during methylmercury intoxication. Biochim Biophys Acta 1334:303–311PubMedGoogle Scholar
  24. 24.
    Juarez BL, Martiez ML, Montante M, Dufour L, Garcia E, Jimenez-Capdeville ME (2002) Methylmercury increases glutamate extracellular levels in frontal cortex of awake rats. Neurotoxicol Teratol 24:767–771PubMedCrossRefGoogle Scholar
  25. 25.
    Gong Z, Evans HL (1997) Effect of chelation with mesodimercaptosuccinic acid (DMSA) before and after the appearance of lead-induced neurotoxicity in the rat. Toxicol Appl Pharmacol 144:205–214PubMedCrossRefGoogle Scholar
  26. 26.
    Cory-Sletcha DA (1997) Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity. Neurotoxicology 18:673–688Google Scholar
  27. 27.
    Raulli RE, Jackson B, Tandon N, Mattson M, Rice K, Jamieson GA (1994) Phencyclidine inhibits epinephrine platelet aggregation independently of high affinity N-methyl-D-aspartate (NMDA)- type glutamatereceptors. Biochim Biophys Acta 1224:175–180PubMedCrossRefGoogle Scholar
  28. 28.
    Soares FA, Farina M, Santos FW, Souza D, Rocha JBT, Nogueira CW (2003) Interaction between metals and chelating agents affects glutamate binding on brain synaptic membranes. Neurochem Res 28:1859–1865PubMedCrossRefGoogle Scholar
  29. 29.
    Trotti D, Nussberger S, Volterra A, Hediger MA (1997) Differential modulation of the uptake in the human neuronal glutamate transporter EAAC1. Eur J Neurosci 9:2207–2212PubMedCrossRefGoogle Scholar
  30. 30.
    Trotti D, Rizzini BL, Rossi D, Haugeto O, Racgani G, Danbolt NC, Volterra A (1997) Neuronal and glial transporters possess an SH-based redox regulatory mechanism. Eur J Neurosci 9:1236–1243PubMedCrossRefGoogle Scholar
  31. 31.
    Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRefGoogle Scholar
  32. 32.
    Lowry OW, Rosenbrough NJ, Farr AL, Randal RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  33. 33.
    Barbeau A, Campanella G, Butterworth RF, Yamada K (1975) Uptake and efflux 14-C- dopamine in platelets: evidence for a generalized defect in Parkinson’s disease. Neurology 25:1–9PubMedGoogle Scholar
  34. 34.
    Zieve PD, Solomon HM (1968) Uptake of amino acids by the human platelets. Am J Physiol 214:58–61PubMedGoogle Scholar
  35. 35.
    Sneddon JM (1973) Blood platelets as a model for monoamine-containing neurons. Prog Neurobiol 1:151–198PubMedCrossRefGoogle Scholar
  36. 36.
    Franconi F, Miceli M, De Montis MG, Crisafi EL, Bennardini F, Tagliamonte A (1996) NMDA receptors play an antiaggreganting role in human platelets. Thromb Haemost 76:84–87PubMedGoogle Scholar
  37. 37.
    Skerry TM, Genever PG (2001) Glutamate signaling in non-neuronal tissues. TiPS 22:174–181PubMedGoogle Scholar
  38. 38.
    Chakrabarti SK, Loua KM, Bai C, Durham H, Panisset J (1998) Modulation of monoamino oxidase activity in different brain regions and platelets following exposure of rats to methylmercury. Neurotoxicol Teratol 20:161–168PubMedCrossRefGoogle Scholar
  39. 39.
    Kim P, Choi BH (1995) Selective inhibition of glutamate uptake by mercury in cultured mouse astrocytes. Yonsei Med J 36:299–305PubMedGoogle Scholar
  40. 40.
    Farina M, Frizzo MES, Soares FAA, Schwalm FD, Dietrich MO, Zeni G, Rocha JBT, Souza DO (2003) Ebseln protects against methylmercury-induced inhibition of glutamate uptake by cortical slices from adult mice. Toxicol Lett 144:351–357PubMedCrossRefGoogle Scholar
  41. 41.
    Moretto MB, Funchal C, Santos AQ, Gottfried C, Boff B, Zeni G, Pessoa-Pureur R, Souza DO, Wofchuk S, Rocha JBT (2005) Ebselen protects glutamate uptake inhibition caused by methyl mercury but does not by Hg2+. Toxicology 214:57–66PubMedCrossRefGoogle Scholar
  42. 42.
    Yang PT, Ellinor WA, Sather JF, Zhang RW (1993) Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels. Nature 366:109–110CrossRefGoogle Scholar
  43. 43.
    Lasley SM, Gilbert ME (2000) Glutamatergic components underlying lead-induced impairments in hippocampal synaptic plasticity. Neurotoxicology 21:1057–1068PubMedGoogle Scholar
  44. 44.
    Strusynska L, Chalimoniuk M, Sulkowski G (2005) Changes in expression of neuronal and glial glutamate transporters in lead-exposed adult rat brain. Neurochem Int 47:326–333CrossRefGoogle Scholar
  45. 45.
    Kom JFM, van der Voet GB, Wolff FA (1998) Mercury exposure of maron workers in the small scale gold mining in Suriname. Environ Res 77:91–97PubMedCrossRefGoogle Scholar
  46. 46.
    Hirata M, Kosaka H, Yoshida T (2004) A study on the effect of lead on event-related potentials among lead-exposed workers. Ind Health 42:431–434PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • V. C. Borges
    • 1
  • F. W. Santos
    • 1
  • J. B. T. Rocha
    • 1
  • C. W. Nogueira
    • 1
  1. 1.Departamento de Química, Centro de Ciencias Naturais e ExatasUniversidade Federal de Santa MariaSanta MariaBrazil

Personalised recommendations