Skip to main content
SpringerLink
Log in

Heavy Metals Modulate Glutamatergic System in Human Platelets

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

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.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schoepp DD, Con PJ (1993) Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol Sci 14:13–20

    Article  PubMed  CAS  Google Scholar 

  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 204:343–354

    Article  PubMed  Google Scholar 

  3. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105

    Article  PubMed  CAS  Google Scholar 

  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 38:73–84

    Article  PubMed  CAS  Google Scholar 

  5. Rossi DJ, Oshima T, Attwell D (2000) Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403:316–321

    Article  PubMed  CAS  Google Scholar 

  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 125:32–43

    Article  PubMed  CAS  Google Scholar 

  7. Manzo L, Castoldi AF, Coccini T, Rossi AD, Nicotera P, Costa LG (1995) Mechanisms of neurotoxicity: applications to human biomonitoring. Toxicol Lett 77:63–72

    Article  PubMed  CAS  Google Scholar 

  8. De Gaetano G, Garattino S (1978) Platelets: a multidisciplinary approach. Raven Press, New York

    Google Scholar 

  9. Mangano RM, Schwarcz R (1981) Platelet glutamate and aspartate uptake in Hungtington’s disease. J Neurochem 37:1072–1074

    Article  PubMed  CAS  Google Scholar 

  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 25:149–157

    Article  PubMed  CAS  Google Scholar 

  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 47:499–506

    Article  PubMed  CAS  Google Scholar 

  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 106:685–692

    Article  PubMed  CAS  Google Scholar 

  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 47:641–643

    Article  PubMed  CAS  Google Scholar 

  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 56:270–272

    PubMed  CAS  Google Scholar 

  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 141:343–347

    Article  PubMed  Google Scholar 

  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 33–74

  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 189–213

    Google Scholar 

  18. Minami A, Takeda A, Nishibaba D, Takefuta S, Oku N (2001) Cadmium toxicity in synaptic neurotransmission in the brain. Brain Res 894:336–339

    Article  PubMed  CAS  Google Scholar 

  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 62:1015–1031

    PubMed  CAS  Google Scholar 

  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 14:253–260

    Article  CAS  Google Scholar 

  21. Aschner M, Yao CP, Allen JW, Tan KW (2000) Methylmercury alters glutamate transport in astrocytes. Neurochem Int 37:199–206

    Article  PubMed  CAS  Google Scholar 

  22. Atchison WD, Hare MF (1994) Mechanisms of methylmercury-induced neurotoxicity. FASEB J 8:622–629

    PubMed  CAS  Google Scholar 

  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 1334:303–311

    PubMed  CAS  Google Scholar 

  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 24:767–771

    Article  PubMed  CAS  Google Scholar 

  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 144:205–214

    Article  PubMed  CAS  Google Scholar 

  26. Cory-Sletcha DA (1997) Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity. Neurotoxicology 18:673–688

    Google Scholar 

  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 1224:175–180

    Article  PubMed  CAS  Google Scholar 

  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 28:1859–1865

    Article  PubMed  CAS  Google Scholar 

  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 9:2207–2212

    Article  PubMed  CAS  Google Scholar 

  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 9:1236–1243

    Article  PubMed  CAS  Google Scholar 

  31. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  32. Lowry OW, Rosenbrough NJ, Farr AL, Randal RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  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 25:1–9

    PubMed  CAS  Google Scholar 

  34. Zieve PD, Solomon HM (1968) Uptake of amino acids by the human platelets. Am J Physiol 214:58–61

    PubMed  CAS  Google Scholar 

  35. Sneddon JM (1973) Blood platelets as a model for monoamine-containing neurons. Prog Neurobiol 1:151–198

    Article  PubMed  CAS  Google Scholar 

  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 76:84–87

    PubMed  CAS  Google Scholar 

  37. Skerry TM, Genever PG (2001) Glutamate signaling in non-neuronal tissues. TiPS 22:174–181

    PubMed  CAS  Google Scholar 

  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 20:161–168

    Article  PubMed  CAS  Google Scholar 

  39. Kim P, Choi BH (1995) Selective inhibition of glutamate uptake by mercury in cultured mouse astrocytes. Yonsei Med J 36:299–305

    PubMed  CAS  Google Scholar 

  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 144:351–357

    Article  PubMed  CAS  Google Scholar 

  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 214:57–66

    Article  PubMed  CAS  Google Scholar 

  42. Yang PT, Ellinor WA, Sather JF, Zhang RW (1993) Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels. Nature 366:109–110

    Article  Google Scholar 

  43. Lasley SM, Gilbert ME (2000) Glutamatergic components underlying lead-induced impairments in hippocampal synaptic plasticity. Neurotoxicology 21:1057–1068

    PubMed  CAS  Google Scholar 

  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 47:326–333

    Article  Google Scholar 

  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 77:91–97

    Article  PubMed  Google Scholar 

  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 42:431–434

    PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Departamento de Química, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil

    V. C. Borges, F. W. Santos, J. B. T. Rocha & C. W. Nogueira

Authors
  1. V. C. Borges
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. W. Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. B. T. Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. W. Nogueira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. W. Nogueira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Borges, V.C., Santos, F.W., Rocha, J.B.T. et al. Heavy Metals Modulate Glutamatergic System in Human Platelets. Neurochem Res 32, 953–958 (2007). https://doi.org/10.1007/s11064-006-9231-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-006-9231-7

Keywords

Search

Navigation