Taurine 3 pp 385-396 | Cite as

Taurine Modulates Glutamate- and Growth Factors-Mediated Signaling Mechanisms

  • A. El Idrissi
  • C. Harris
  • E. Trenkner
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 442)


In the central nervous system, the formation and maintenance of neuronal connections are regulated, in part, through a balanced interaction between intracellular and extracellular signals. Under physiological conditions, these signals regulate neuronal maturation, survival and function. Slight changes of this balance however, result in significant functional and structural changes, leading to pathological conditions, loss of function and subsequently to cell death. Prominent among these signals are growth factors and neuroactive amino acids (NAAs). The purpose of these studies was to examine the combined effects of growth factors (Gfs) and neuroactive amino acids (NAAs) on mouse cerebellar granule cells (CGC) survival, energy-metabolism, calcium homeostasis, and protein phosphorylation. We have demonstrated that taurine at physiological concentrations had a neurotrophic effect and protected neurons against glutamate excitotoxicity. These effects were partially mediated through the modulation of intracellular calcium homeostasis34,17. Here we report that also cellular energy metabolism was affected by taurine. Furthermore, as a consequence of its calcium modulatory role, taurine regulated protein kinase C (PKC) activity during glutamate depolarization. Finally, taurine down-regulated the glutamate-induced phosphorylation of a specific set of proteins. We further demonstrated that these various effects of taurine were selectively modulated by brain-derived neurotropic factor (BDNF) and basic fibroblast growth factor (bFGF), suggesting that NAAs, the mitochondrial energy-metabolism and growth factors together regulate neuronal survival and function. It is, therefore, of considerable importance to identify the different environmental signals that interact to regulate the development and maintenance of the integrity of neuronal functions, in order to better understand mechanisms that could lead to abnormal development.


Cerebellar Granule Cell Glutamate Excitotoxicity Glutamate Neurotoxicity Cerebellar Cell Balance Interaction 
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  1. 1.
    Barde, Y-A., 1989, Trophic factors and neuronal survival, Neuron, 2:1525–1534.PubMedCrossRefGoogle Scholar
  2. 2.
    Beal, M.F., 1995, Aging, energy, and oxidative stress in neurodegenerative diseases, Ann. Neuol., 18:357–366.CrossRefGoogle Scholar
  3. 3.
    Bottenstein, J.E., Skaper, S.D., Varon, S.S., and Sato, G.H., 1980, Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium, Exp. cell Res., 125:183–190.PubMedCrossRefGoogle Scholar
  4. 4.
    Budd, S.L. and Nicholls, D.G., 1995, Protein kinase C-mediated suppression of the presynaptic adenosine A1 receptor by a faciliatory metabotropic glutamate receptor, J. Neurochem., 65:615–621.PubMedCrossRefGoogle Scholar
  5. 5.
    Budd, S.L. and Nicholls, D.G., 1995, A reevaluation of the role of mitochondria in neuronal Ca2+ homeostasis, J. Neurochem., 66:403–411.CrossRefGoogle Scholar
  6. 6.
    Budd, S.L. and Nicholls, D.G., 1996, Mitochondria, calcium regulation, and acute glutamate excitotoxicity in cultured cerebellar granule cells, J. Neurochem., 67:2282–2291.PubMedCrossRefGoogle Scholar
  7. 7.
    Budd, S.L., Castilho, R.F., and Nicholls, D.G., 1997, Mitochondrial membrane potential and hydroethidine-monitored Superoxide generation in cultured cerebellar granule cells, FEBS Lett., 415:21–24.PubMedCrossRefGoogle Scholar
  8. 8.
    Chen, L.B., 1989, Fluorescent labeling of mitochondria, Methods in Cell Biology, 29:103–123.PubMedCrossRefGoogle Scholar
  9. 9.
    Cheng, B. and Mattson, M.P., 1991, NGF and bFGF protect rat hippocampal and human cortical neurons against hypoglycwemic damage by stabilizing calcium homeostasis, Neuron, 7:1031–1041.PubMedCrossRefGoogle Scholar
  10. 10.
    Choi, D.W., 1987, Ionic dependence of glutamate neurotoxicity, J. Neurosci., 7:369–379.PubMedGoogle Scholar
  11. 11.
    Choi, D.W., 1988, Glutamate neurotoxicity and diseases of the nervous system, Neuron, 1:623–634.PubMedCrossRefGoogle Scholar
  12. 12.
    Choi, D.W., 1990, The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Ann. Rev. Neurosci., 13:171–182.PubMedCrossRefGoogle Scholar
  13. 13.
    Coffey, E.T., Sihra, T.S., and Nicholls, D.G., 1993, Protein kinase C and the regulation of glutamate exocytosis from cerebrocortical synaptosomes, J. Biol. Chem., 26S:21060–21065.Google Scholar
  14. 14.
    Eboli, M.L., Mercanti, D., Ciotti, M.T., Aquino, A., and Castellani, L., 1994, Glutamate-induced protein phosphorylation in cerebellar granule cells: role of protein kinase C, Neurochem, Res., 19:1257–1264.CrossRefGoogle Scholar
  15. 15.
    Eimerl, S. and Schramm, M., 1993, Resuscitation of brain neurons in the presence of Ca2+ after toxic NMDA receptor activity, J. Neurochem., 61:518–525.PubMedCrossRefGoogle Scholar
  16. 16.
    Eimerl, S. and Schramm, M., 1995, Resuscitation of brain neurons in the presence of Ca2+after toxic NMDA-receptor activity, J. Neurochem., 65:739–734.PubMedCrossRefGoogle Scholar
  17. 17.
    El Idrissi, A., Harris, A., and Trenkner, E. 1996, Neurotrophins, neuro-active amino acids and the mitochondrial respiratory chain together maintain neuronal survival and function, Abstr. Soci. Neurosci., 22:770.11Google Scholar
  18. 18.
    Farago, A. and Nishizuka, Y., 1990, Protein kinase C in transmembrane signaling, FEBS Lett., 268:350–354.PubMedCrossRefGoogle Scholar
  19. 19.
    Foster, A.C., Gill, R. and Woodruff, G.N., 1988, Neuroprotective effects of MK801 in vivo: selectivity and evidence for delayed degeneration mediated by NMDA receptor activation, J. Neurosci., 8:4745–4754.PubMedGoogle Scholar
  20. 20.
    Hartley, D.M., Kurth, M.C., Bjerkness, L., Weiss, J.H., and Choi, D.W., 1993, Glutamate receptor-induced 45Ca2+ accumulation in cortical cell culture correlates with subsequent neuronal degeneration, J. Neurosci., 13:1993–2000.PubMedGoogle Scholar
  21. 21.
    Huxtable, R.J., 1992, The physiological actions of taurine, Physiol. Rev., 72:101–163.PubMedGoogle Scholar
  22. 22.
    Gill, R., Foster, A.C., and Woodruff, G.N., 1987, Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil, J. Neurosci., 7:3343–3349.PubMedGoogle Scholar
  23. 23.
    Lombardini, J.B., 1994, The inhibitory effects of taurine on protein phosphorylation: comparisons of various characteristics of the taurine-affected phosphoproteins present in rat retina, brain and heart, in: Adv. Exp. Med. Biol. “Health and Disease”, Michalk, D.V. and Huxtable, R.J., eds., Plenum Press, New York, Vol. 359, pp 9–17.Google Scholar
  24. 24.
    Mattson, M.P., 1988, Neurotransmitters in the regulation of cytoarchitecture, Brain Res. Rev., 13:179–212.CrossRefGoogle Scholar
  25. 25.
    Mattson, M.P. and Cheng, B., 1993, Growth factors protect neurons against excitotoxic/ ischwemic damage by stabilizing calcium homeostasis, Stroke, 24:1136–1140.Google Scholar
  26. 26.
    Mattson, M.P., Zhang, Y., and Bose, S., 1993, Growth factors prevent mitochondrial dysfunction, loss of calcium homeostasis, and cell injury, but not ATP depletion in hippocampal neurons deprived of glucose, Exp. Neurol., 121:1–13.PubMedCrossRefGoogle Scholar
  27. 27.
    Nishizuka, Y., 1988, The molecular heterogeneity of protein kinase C and its implications for cellular regulation, Nature. 334:661–665.PubMedCrossRefGoogle Scholar
  28. 28.
    Nishizuka, Y., 1988, The heterogeneity and differential expression of multiple species of the protein kinase C family, Biofactors, 1:17–20.PubMedGoogle Scholar
  29. 29.
    Squinto, S.P., Stitt, T.N., Aldrich, T.H., Davis, S., Bianco, S.M., Radziejewski, C., Glass, D.J., Masiakowski, P., Furth, M.E., and Valenzuela, D.M., 1991, TrkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor, Cell, 65:885–893.PubMedCrossRefGoogle Scholar
  30. 30.
    Sturman, J.A., 1993, Taurine in development, Physiol Rev., 73:119–147.PubMedGoogle Scholar
  31. 31.
    Trenkner, E. and Sidman, R.L., 1977, Histogenesis of mouse cerebellum in microwell cultures: cell reaggregation and migration, fiber and synapse formation, J. Cell. Biol., 75:915–940.PubMedCrossRefGoogle Scholar
  32. 32.
    Trenkner, E., 1991, Cerebellar cells in culture, in: Culturing Nerve Cells, Banker, G. and Goslin, K. eds., MIT Press, pp. 283-307.Google Scholar
  33. 33.
    Trenkner, E., Liu, D.J., Harris, C., and Sturman, J.A., 1994, Regulation of protein kinase C activity by taurine and β-alanine during excitotoxicity in cat and mouse cerebellar cultures, in: Adv. Exp. Med. Biol. “Health and Disease”, Michalk, D.V. and Huxtable, R.J., eds., Plenum Press, New York, Vol. 359, pp. 309–316.Google Scholar
  34. 34.
    Trenkner, E., El Idrissi, A., and Harris, C., 1996, Balanced interaction of growth factors and taurine regulate energy metabolism, neuronal survival and function of mouse cerebellar granule cells under depolarizing conditions, in: Adv. Exp. Med. Biol. “Taurine 2”, Huxtable, R.J., Azuma, J., Kuriyama, K., Nakagawa, M., and Baba, A., eds., Plenum Press, New York, Vol. 403:507-517.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • A. El Idrissi
    • 1
    • 2
  • C. Harris
    • 3
  • E. Trenkner
    • 1
    • 2
  1. 1.CUNY Graduate School and University CenterNew YorkUSA
  2. 2.New York State Institute for Basic Research and Developmental DisabilitiesStaten IslandUSA
  3. 3.CSI / IBR Center for Developmental Neuroscience and Developmental DisabilitiesStaten IslandUSA

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