Skip to main content
SpringerLink
Log in

NMDA-dependent superoxide production and neurotoxicity

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

NEURONAL injury resulting from acute brain insults and some neurodegenerative diseases implicates N-methyl-D-aspartate (NMDA) glutamate receptors1–4. The fact that antioxidants reduce some types of brain damage suggests that oxygen radicals may have a role5–7. It has been shown that mutations in Cu/Zn-superoxide dismutase (SOD), an enzyme catalysing superoxide (O·-2) detoxification in the cell, are linked to a familial form of amyotrophic lateral sclerosis (ALS)4. Here we report that O·-2 is produced upon NMDA receptor stimulation in cultured cerebellar granule cells. Electron paramagnetic resonance was used to assess O·-2 production that was due in part to the release of arachidonic acid. Activation of kainic acid receptors, or voltage-sensitive Ca2+ channels, did not produce detectable O·-2. We also find that the nitrone DMPO (5,5-dimethyl pyrroline 1-oxide), used as a spin trap, is more efficient than the nitric oxide synthase inhibitor, L-NG-nitroarginine, in reducing NMDA-induced neuronal death in these cultures.

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

Similar content being viewed by others

References

  1. Choi, D. W. Neuron 1, 623–634 (1988).

    Article  CAS  Google Scholar 

  2. Olney, J. W. Drug Dev. Res. 17, 299–319 (1989).

    Article  CAS  Google Scholar 

  3. Meldrum, B. S. & Garthwaite, J. Trends pharmac. Sci. 11, 379–387 (1990).

    Article  CAS  Google Scholar 

  4. Rosen, D. R. et al. Nature 362, 59–62 (1993).

    Article  ADS  CAS  Google Scholar 

  5. Saez, J. C., Kessler, J. A., Bennett, M. V. L. & Spray, D. C. Proc. natn. Acad. Sci. U.S.A. 84, 3056–3059 (1987).

    Article  ADS  CAS  Google Scholar 

  6. Monyer, H., Hartley, D. M. & Choi, D. W. Neuron 5, 121–126 (1990).

    Article  CAS  Google Scholar 

  7. Pellegrini-Giampietro, D. E., Cherici, G., Alesiani, M., Carla, V. & Moroni, F. J. Neurosci. 10, 1035–1041 (1990).

    Article  CAS  Google Scholar 

  8. Finkelstein, E., Rosen, G. M. & Rauckman, E. J. Arch. Biochem. Biophys. 200, 1–16 (1980).

    Article  CAS  Google Scholar 

  9. Dumuis, A., Sebben, M., Haynes, H., Pin, J.-P. & Bockaert, J. Nature 336, 68–70 (1988).

    Article  ADS  CAS  Google Scholar 

  10. Rosen, G. M. & Finkelstein, E. Adv. free Rad. Biol. Med. 1, 345–375 (1985).

    Article  CAS  Google Scholar 

  11. Rosen, G. M. & Turner, M. J. III, J. med. Chem. 31, 428–432 (1988).

    Article  CAS  Google Scholar 

  12. Pou, S. et al. Analyt. Biochem. 177, 1–6 (1989).

    Article  CAS  Google Scholar 

  13. Didier, M., Heaulme, M., Gonalons, N., Soubrié, P. & Pin, J.-P. Eur. J. Pharmac. 224, 57–65 (1993).

    Article  Google Scholar 

  14. Mayer, M. L. & Miller, R. J. Trends Neurosci. 11, 254–260 (1990).

    CAS  Google Scholar 

  15. Traystman, R. J., Kirsch, J. R. & Koehler, R. C. J. appl. Physiol. 71, 1185–1195 (1991).

    Article  CAS  Google Scholar 

  16. Heinzel, B., John, M., Klatt, P., Böhme, E. & Mayer, B. Biochem. J. 281, 627–630 (1992).

    Article  CAS  Google Scholar 

  17. Pou, S., Pou, W. S., Bredt, D. S., Snyder, S. H. & Rosen, G. M. J. biol. Chem. 267, 24173–24176 (1992).

    CAS  PubMed  Google Scholar 

  18. Dawson, V. L., Dawson, T. M., London, E. D., Bredt, D. S. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 88, 6368–6371 (1992).

    Article  ADS  Google Scholar 

  19. Lerner-Natoli, M., Rondouin, G., de Bock, F. & Bockaert, J. NeuroReport 3, 1109–1112 (1992).

    Article  CAS  Google Scholar 

  20. Nowicki, J. P., Duval, D., Poignet, H. & Scatton, B. Eur. J. Pharmac. 204, 339–340 (1992).

    Article  Google Scholar 

  21. Moncada, C., Lekieffre, D., Arvin, B. & Meldrum, B. NeuroReport 3, 530–532 (1992).

    Article  CAS  Google Scholar 

  22. Pauwels, P. J. & Leysen, J. E. Neurosci. Lett. 143, 27–30 (1992).

    Article  CAS  Google Scholar 

  23. Garthwaite, J. Trends Neurosci. 14, 60–67 (1991).

    Article  CAS  Google Scholar 

  24. Bredt, D. S. & Snyder, S. H. Neuron 8, 3–11 (1992).

    Article  CAS  Google Scholar 

  25. Van Vliet, B. J. et al. J. Neurochem. 52, 1229–1239 (1989).

    Article  CAS  Google Scholar 

  26. Didier, M., Heaulme, M., Soubrié, P., Bockaert, J. & Pin, J.-P. J. neurosci. Res. 27, 25–35 (1990).

    Article  CAS  Google Scholar 

  27. Lafon-Cazal, M., Bougault, I., Steinberg, R., Pin, J. P. & Bockaert, J. Brain Res. 593, 63–68 (1992).

    Article  CAS  Google Scholar 

  28. Favaron, M. et al. Proc. natn. Acad. Sci. U.S.A. 87, 1983–1987 (1989).

    Article  ADS  Google Scholar 

  29. Marin, P., Lafon-Cazal, M. & Bockaert, J. Eur. J. Neurosci. 4, 425–432 (1992).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre CNRS-INSERM de Pharmacologie-Endocrinologie, rue de la Cardonille, 34094, Montpellier, Cedex 5, France

    Mireille Lafon-Cazal & Joel Bockaert

  2. CRIPDOM, PO Box 43, 34172, Castelnau-le Lez Cedex, France

    Sylvia Pietri & Marcel Culcasi

  3. SREP-CNRS URA 1412, Université de Provence, 13397, Marseille, Cedex 13, France

    Sylvia Pietri & Marcel Culcasi

Authors
  1. Mireille Lafon-Cazal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sylvia Pietri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcel Culcasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joel Bockaert
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lafon-Cazal, M., Pietri, S., Culcasi, M. et al. NMDA-dependent superoxide production and neurotoxicity. Nature 364, 535–537 (1993). https://doi.org/10.1038/364535a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/364535a0

  • Springer Nature Limited

This article is cited by

Search

Navigation