Abstract
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.
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References
Barde, Y-A., 1989, Trophic factors and neuronal survival, Neuron, 2:1525–1534.
Beal, M.F., 1995, Aging, energy, and oxidative stress in neurodegenerative diseases, Ann. Neuol., 18:357–366.
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.
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.
Budd, S.L. and Nicholls, D.G., 1995, A reevaluation of the role of mitochondria in neuronal Ca2+ homeostasis, J. Neurochem., 66:403–411.
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.
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.
Chen, L.B., 1989, Fluorescent labeling of mitochondria, Methods in Cell Biology, 29:103–123.
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.
Choi, D.W., 1987, Ionic dependence of glutamate neurotoxicity, J. Neurosci., 7:369–379.
Choi, D.W., 1988, Glutamate neurotoxicity and diseases of the nervous system, Neuron, 1:623–634.
Choi, D.W., 1990, The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Ann. Rev. Neurosci., 13:171–182.
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.
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.
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.
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.
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., 22:770.11
Farago, A. and Nishizuka, Y., 1990, Protein kinase C in transmembrane signaling, FEBS Lett., 268:350–354.
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.
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.
Huxtable, R.J., 1992, The physiological actions of taurine, Physiol. Rev., 72:101–163.
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.
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.
Mattson, M.P., 1988, Neurotransmitters in the regulation of cytoarchitecture, Brain Res. Rev., 13:179–212.
Mattson, M.P. and Cheng, B., 1993, Growth factors protect neurons against excitotoxic/ ischwemic damage by stabilizing calcium homeostasis, Stroke, 24:1136–1140.
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.
Nishizuka, Y., 1988, The molecular heterogeneity of protein kinase C and its implications for cellular regulation, Nature. 334:661–665.
Nishizuka, Y., 1988, The heterogeneity and differential expression of multiple species of the protein kinase C family, Biofactors, 1:17–20.
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.
Sturman, J.A., 1993, Taurine in development, Physiol Rev., 73:119–147.
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.
Trenkner, E., 1991, Cerebellar cells in culture, in: Culturing Nerve Cells, Banker, G. and Goslin, K. eds., MIT Press, pp. 283-307.
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.
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.
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Idrissi, A.E., Harris, C., Trenkner, E. (1998). Taurine Modulates Glutamate- and Growth Factors-Mediated Signaling Mechanisms. In: Schaffer, S., Lombardini, J.B., Huxtable, R.J. (eds) Taurine 3. Advances in Experimental Medicine and Biology, vol 442. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0117-0_48
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DOI: https://doi.org/10.1007/978-1-4899-0117-0_48
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