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The Role of Taurine in the Central Nervous System and the Modulation of Intracellular Calcium Homeostasis

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Abstract

The effects of taurine in the mammalian nervous system are numerous and varied. There has been great difficulty in determining the specific targets of taurine action. The authors present a review of accepted taurine action and highlight recent discoveries regarding taurine and calcium homeostasis in neurons. In general there is a consensus that taurine is a powerful agent in regulating and reducing the intracellular calcium levels in neurons. After prolonged L-glutamate stimulation, neurons lose the ability to effectively regulate intracellular calcium. This condition can lead to acute swelling and lysis of the cell, or culminate in apoptosis. Under these conditions, significant amounts of taurine (mM range) are released from the excited neuron. This extracellular taurine acts to slow the influx of calcium into the cytosol through both transmembrane ion transporters and intracellular storage pools. Two specific targets of taurine action are discussed: Na+-Ca2+ exchangers, and metabotropic receptors mediating phospholipase-C.

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REFERENCES

  1. Maar, T. E., Lund, T. M., Gegelashvili, G., Hartmann-Petersen, R., Moran, J., Pasantes-Morales, H., Berezin, V., Bock, E., and Schousboe, A. 1998. Effects of taurine depletion on cell migration and NCAM expression in cultures of dissociated mouse cerebellum and N2A cells. Amino Acids. 15(1–2):77–88.

    Google Scholar 

  2. Bruhn, T., Christensen, T., Cobo, M., Damgaard, I., Diemer, N. H., and Schousboe A. 1996. Effects of phenylsuccinate on potassium-stimulated taurine release in cultured neurons and astrocytes and in rat hippocampus in vivo. J. Neurosci. Res. 46(2):198–203.

    Google Scholar 

  3. Jacobsen, J. G. and Smith, L. H. 1968. Biochemistry and physiology of taurine and taurine derivatives. Physiol. Rev. 48:24–511.

    Google Scholar 

  4. Hayes, K. C., Carey, R. E., and Schmidt, S. Y. 1975. Retinal degeneration associated with taurine deficiency in the cat. Science 188:949–951.

    Google Scholar 

  5. Pion, P. D., Kittleson, M. D., Rogers, Q. R., and Morris, J. G. 1987. Myocardial failure in cats associated with low plasma taurine: A reversible cardiomyopathy. Science 237:764–768.

    Google Scholar 

  6. Sturman, J. A. 1993. Taurine in development. Physiol. Rev. 73: 119–147.

    Google Scholar 

  7. Moran, J., Salazar, P., and Pasantes-Morales, H. 1988. Effect of tocopherol and taurine on membrane fluidity of retinal rod outer segments. Experimental Eye Research. 45:769–776.

    Google Scholar 

  8. Lazarewicz, J. W., Noremberg, K., Lehmann, A., and Hamberger, A. 1985. Effects of taurine on calcium binding and accumulation in rabbit hippocampal and cortical synaptosomes. Neurochem. Int. 7:421–428.

    Google Scholar 

  9. Lombardini, J. B. 1985. Effects of taurine on calcium ion uptake and protein phosphorylation in rat retinal membrane preparations. J. Neurochem. 45:268–275.

    Google Scholar 

  10. Solia, J. M., Herranz, A. S., Herreras, O., Lerma, J., and Del Rio, R. M. 1988. Does taurine act as an osmoregulatory substance in the rat brain. Neurosci. Lett. 91:53–58.

    Google Scholar 

  11. Wade, J. V., Olson, J. P., Samson, F. E., Nelson, S. R., and Pazdernik, T. L. 1988. A possible role for taurine in osmoregulation within the brain. J. Neurochem. 51:740–745.

    Google Scholar 

  12. Schaffer, S., Takahashi, K., and Azuma, J. 2000. Role of osmoregulation in the actions of taurine. Amino Acids. 19(3–4):527–546.

    Google Scholar 

  13. Kuriyama, K. 1980. Taurine as a neuromodulator. Fed. Proc. 39:2680–2684.

    Google Scholar 

  14. Okamoto, K., Kimura, H., and Sakai, Y. 1983. Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: Selective antagonism by TAG (6–aminomethyl-3–methyl-4H, 1, 2,4–benzothiadiazine-1,1–dioxide). Brain Res. 265(1):163–168.

    Google Scholar 

  15. Lin, C.-T., Su, Y. Y. T., Song, G.-X., and Wu, J.-Y. 1983. Is taurine a neurotransmitter in rabbit retina? Brain Res. 337:293–298.

    Google Scholar 

  16. Lombardini, J. B., Schaffer, S. W., and Azuma, J. (eds). 1992. Taurine: Nutritional Value and Mechanisms of Action. Adv. Expt. Med. & Biol. 315:1–441.

  17. Taber, T. C., Lin, C.-T., Song, G.-X., Thalman, R. H., and Wu, J.-Y. 1986. Taurine in the rat hippocampus-localization and postsynaptic action. Brain Res. 386:113–121.

    Google Scholar 

  18. Cunningham, R. and Miller, R. F. 1976. Taurine: Its selective action on neuronal pathways in the rabbit retina. Brain Res. 117:341–345.

    Google Scholar 

  19. Mandel, P., Pasantes-Morales, H., and Urban, P. F. 1976. Taurine, a putative transmitter in retina. Pages 89–105, in S. L. Bontig (ed.), Transmitters in the Visual Process, Pergamon, Oxford.

    Google Scholar 

  20. Lin, C.-T., Song, G.-X., and Wu, J.-Y. 1985. Ultrastructural demonstration of L-glutamate decarboxylase and cysteinesulfinic acid decarboxylase in rat retina by immunocytochemistry. Brain Res. 331:71–80.

    Google Scholar 

  21. Lin, C.-T., Li, H.-Z., and Wu, J.-Y. 1983. Immunocytochemical localization of L-glutamate decarboxylase, gamma aminobutyric acid transaminase, cysteine-sulfinic acid decarboxylase, aspartate aminotransferase and somatostatin in rat retina. Brain Res. 270:273–283.

    Google Scholar 

  22. Tang, X. W., Deupree, D. L., Sun, Y., and Wu, J.-Y. 1996. Biphasic effect of taurine on excitatory amino acid-induced neurotoxicity. Pages 499–506, in R. J. Huxtable, J. Azuma, M. Nakagawa, K. Kuriyama, and A. Bala, (eds.), Taurine: Basic and Clinical Aspects, Plenum Publishing Co.

  23. El Edrissi, A. and Trenkner, E. 1999. Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. J. Neurosci. 19:9459–9468.

    Google Scholar 

  24. Saransari, P. and Oja, S. S. 2000. Taurine and neural cell damage. Amino Acids. 19(3–4):509–526.

    Google Scholar 

  25. Chan-Palay, V., Palay, S. L., Li, C., and Wu, J.-Y. 1982. Sagittal cerebellar micro-bands of taurine neurons: Immunocytochemical demonstration by using antibodies against the taurine synthesizing enzyme cysteinesulfinic acid decarboxylase. Proc. Natl. Acad. Sci. USA 79:4221–4225.

    Google Scholar 

  26. Magnusson, K. R., Madl, J. E., Clements, J. R., Wu, J.-Y., Larson, A. A., and Beitz, A. J. 1988. Co-localization of taurine-and cysteine sulfinic acid decarboxylase-like immunoreactivity in the cerebellum of the rat with the use of a novel monoclonal antibody against taurine. J. Neurosci. 8(12):4551–4564.

    Google Scholar 

  27. Magnusson, K. R., Clements, J. R., Wu, J.-Y., and Beitz, A. J. 1989. Co-localization of taurine-and cysteine sulfinic acid decarboxylase-like immunoreactivity in the hippocampus of the rat. Synapse 4:55–69.

    Google Scholar 

  28. Del Arco, A., Segovia, G., Prieto, L., and Mora, F. 2001. Endogenous glutamate-taurine interaction in striatum and nucleus accumbens of the freely moving rat: studies during the normal process of aging. Mech. Ageing Dev. 122(4):401–414.

    Google Scholar 

  29. Okada, M., Okuma, Y., Osumi, Y., Nishihara, M., Yokotani, K., Ueno, H. 2000. Neurotransmitter contents in the retina of RCS rats. Graefes Arch. Clin. Exp. Ophthalmol. 238(12):998–1001.

    Google Scholar 

  30. Hassel, B., Tauboll, E., and Gjerstad, L. 2001. Chronic lamotrigine treatment increases rat hippocampal GABA shunt activity and elevates cerebral taurine levels. Epilepsy Res. 43(2): 153–163.

    Google Scholar 

  31. Peck, E., Jr. and Awapara, J. 1967. Formation of taurine and isethionic acid in rat brain. Biochim. Biophys. Acta. 141: 499–506.

    Google Scholar 

  32. Sumiz, K. 1962. Oxidation of hypotaurine in rat liver. Biochim. Biophys. Acta. 63:210–212.

    Google Scholar 

  33. Davison, A. N. 1956. Amino acid decarboxylases in rat brain and liver. Biochim. Biophys. Acta. 234:107–108.

    Google Scholar 

  34. Wu, J.-Y. 1982. Purification and characterization of cysteic/cysteinesulfinic acids decarboxylase and L-glutamate decarboxylase in bovine brain. Proc. Natl. Acad. Sci. USA 79:4270–4274.

    Google Scholar 

  35. Blinderman, J. M., Maitre, M., Ossola, L., and Mandel, P. 1978. Purification and some properties of L-glutamate decarboxylase from human brain. Eur. J. Biochem. 86:143–152.

    Google Scholar 

  36. Wu, J.-Y., Su, Y. Y. T., Brandon, C., Lam, D. M. K., Chen, M. S., and Huang, W. M. 1979. Purification and immunochemical studies of GABA-, acetylcholine-and taurine-synthesizing enzymes from bovine and fish brains. Seventh International Meeting of the ISN, p. 662.

  37. Oertel, W. H., Schmechel, D. E., Weise, V. K., Ransom, D. H., Tappaz, M. L., Krutzsch, H. C., and Kopin, I. J. 1981. Comparison of cysteine sulfinic acid decarboxylase isoenzymes and glutamic acid decarboxylase in rat liver and brain. Neuroscience. 6:2701–2714.

    Google Scholar 

  38. Tappaz, M., Almarghini, K., Legay, F., and Remy, A. 1992. Taurine biosynthesis enzyme cysteine sulfinate decarboxylase (CSD) from brain: the long and tricky trail to identification. Neurochem. Res. 17:849–859.

    Google Scholar 

  39. Almarghini, K., Remy, A., and Tapaz, M. 1991. Immunocytochemistry of the taurine biosynthesis enzyme, cysteine sulfinate decarboxylase in the cerebellum. Evidence for a glial localization. Neuroscience. 43:111–119.

    Google Scholar 

  40. Reymond, I., Almarghini, K., and Tappaz, M. 1996. Immunocytochemical localization of cysteine sulfinate decarboxylase in astrocytes in the cerebellum and hippocampus: a quantitative double immunofluorescence study with glial fibrillary acidic protein and S-100 protein. Neuroscience. 75:619–633.

    Google Scholar 

  41. Almarghini, K., Barbagli, B., and Tappaz, M. 1994. Production and characterization of a new specific antiserum against the taurine putative biosynthetic enzyme cysteine sulfinate decarboxylase. J. Neurochem. 62:1604–1614.

    Google Scholar 

  42. Pasantes-Morales, H., Chatagner, F., and Mandel, P. 1980. Synthesis of taurine in rat liver and brain in vivo. Neurochem. Res. 5:441–451.

    Google Scholar 

  43. Tappaz, M., Bitoun, M., Reymond, I., and Sergeant, A. 1999. Characterization of the cDNA coding for rat brain cysteine sulfinate decarboxylase: brain and liver enzymes are identical proteins encoded by two distinct mRNAs. J. Neurochem. 73:903–912.

    Google Scholar 

  44. Kaisaki, P. J., Jerkins, A. A., Goodspeed, D. C., Steele, R. D., and Kaisakia, P. J. 1995. Cloning and characterization of rat cysteine sulfunic acid decarboxylase. Biochim. Biophys. Acta. 1262:79–82.

    Google Scholar 

  45. Reymond, L., Sergeant, A., and Tappaz, M. 1996. Molecular cloning and sequence analysis of the cDNA encoding rat liver cysteine sulfinate decarboxylase (CSD). Biochim. Biophys. Acta. 1307:152–156.

    Google Scholar 

  46. Erlander, M. G. and Tobin, A. J. 1991. The structure and functional heterogeneity of glutamic acid decarboxylase: A review. Neurochem. Res. 16:215–226.

    Google Scholar 

  47. Nathan, B., Bao, J., Hsu, C.-C., Aguilar, P., Wu, R., Yarom, M., Kuo, C.-Y., and Wu, J.-Y. 1994. A membrane form of brain L-glutamate decarboxylase: identification, isolation and its relation to insulin-dependent diabetes mellitus. Proc. Natl. Acad. Sci. (USA). 91:242–246.

    Google Scholar 

  48. Nathan, B., Hsu, C.-C., Bao, J., Wu, R., and Wu, J.-Y. 1994. Purification and characterization of a novel form of brain L-glutamate decarboxylase-A Ca2+-dependent peripheral membrane protein. J. Biol. Chem. 269:7249–7254.

    Google Scholar 

  49. Nathan, B., Bao, J., Hsu, C. C., Yarom, M., Deupree, D. L., Lee, Y. H., Tang, X. W., Kuo, C. Y., Burghen, G. A., and Wu, J.-Y. 1994. An integral membrane protein form of brain L-glutamate Taurine: Synthesis and Its Role in Calcium Homeostasis 25 decarboxylase-purification and characterization. Brain Res. 642:297–302.

    Google Scholar 

  50. Tang, X. W., Hsu, C.-C., Sun, Y., Wu, E., Yang, C. Y., and Wu, J.-Y. 1997. Protein phosphorylation and taurine biosynthesis in vivo and in vitro. J. Neurosci. 17:6947–6951.

    Google Scholar 

  51. Foos, T. and Wu, J.-Y. 2000. The cloning and characterization of two soluble forms of brain cysteine sulfinic acid decarboxylase. J. Neurochem. 74: supple. S38C.

    Google Scholar 

  52. Ramamoorthy, S., Del-Monte, M. A., Leibach, F. H., and Ganapathy, V. 1994. Molecular identity and calmodulin-mediated regulation of the taurine transporter in a human retinal pigment epithelial cell line. Curr. Eye Res. 13:523–529.

    Google Scholar 

  53. Uchida, S., Kwon, H. M., Yamauchi, A., Preston, A. S., Marumo, F., and Handler, J. S. 1992. The molecular cloning of the cDNA for an MDCK cell Na(1)-and Cl(2)-dependent taurine transporter that is regulated by hypertonicity. Proc. Natl. Acad. Sci. USA 89:8230–8234.

    Google Scholar 

  54. Jessen, H. 1994. Taurine and beta-alanine transport in an established human kidney cell line derived from the proximal tubule. Biochim. Biophys. Acta. 1194:44–52.

    Google Scholar 

  55. Chung, S. J., Ramanathan, V., Giacomini, K. M., and Brett, C. M. 1994. Characterization of a sodium-dependent taurine transporter in rabbit choroid plexus. Biochim. Biophys. Acta. 1193:10–16.

    Google Scholar 

  56. Ramamoorthy, S., Leibach, F. H., Mahesh, V. B., Han, H., Yang-Feng, T. Blakely, R. D., and Ganapathy, V. 1994. Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem. J. 300:893–900.

    Google Scholar 

  57. Jhiang, S. M., Fithian, L., Smanik, P., McGill, J., Tang, W., and Mazzaferri, E. L. 1993. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett. 318:139–44.

    Google Scholar 

  58. Brandsch, M., Miyamoto, Y., Ganapathy, V., and Leibach, F. H. 1993. Regulation of taurine transport in human colon carcinoma cell lines (HT-29 and Caco-2) by protein kinase C. Am. J. Physiol. 264:G939–G946.

    Google Scholar 

  59. Liu, Q. R., Lopez-Corcuera, B., Nelson, H., Mandiyan, S., and Nelson, N. 1992. Cloning and expression of a cDNA encoding the transporter of taurine and beta-alanine in mouse brain. Proc. Natl. Acad. Sci. USA 89:12145–12149.

    Google Scholar 

  60. Smith, K. E., Borden, L. A., Wang, C. H., Hartig, R. R. Branchek, T. A., and Weinshank, R. L. 1992. Cloning and expressing of a high affinity taurine transporter from rat brain. Mol. Pharmacol. 42:563–569.

    Google Scholar 

  61. Bitoun, M. and Tappaz, M. 2000. Taurine down-regulates basal and osmolarity-induced gene expression of its transporter, but not the gene expression of its biosynthetic enzymes, in astrocyte primary cultures. J. Neurochem. 3:919–924.

    Google Scholar 

  62. Beetsch, J. W. and Olson, J. E. 1998. Taurine synthesis and cysteine metabolism in cultured rat astrocytes: effects of hyperosmotic exposure. Am J. Physiol. 274(4 Pt 1):C866–874.

    Google Scholar 

  63. Bitoun, M. and Tappaz, M. 2000. Gene expression of the transporters and biosynthetic enzymes of the osmolytes in astrocyte primary cultures exposed to hyperosmotic conditions. Glia 32(2):165–176.

    Google Scholar 

  64. Bitoun, M. and Tappaz, M. 2000. Taurine down-regulates basal and osmolarity-induced gene expression of its transporter, but not the gene expression of its biosynthetic enzymes, in astrocyte primary cultures. J. Neurochem. 75(3):919–924.

    Google Scholar 

  65. Bitoun, M. and Tappaz, M. 2000. Gene expression of taurine transporter and taurine biosynthetic enzymes in brain of rats with acute or chronic hyperosmotic plasma: a comparative study with gene expression of myo-inositol transporter, betaine transporter and sorbitol biosynthetic enzyme. Brain Res. Mol. Brain Res. 77(1):10–18.

    Google Scholar 

  66. Jerkins, A. A. and Steele, R. D. 1992. Quantification of cysteine sulfinic acid decarboxylase in male and female rats: effect of adrenalectomy and methionine. Arch. Biochim. Biophys. 294:534–538.

    Google Scholar 

  67. Jerkins, A. A. and Steele, R. D. 1991. Dietary sulfur amino acid modulation of cysteine sulfinic acid decarboxylase. Am. J. Physiol. 261:551–555.

    Google Scholar 

  68. Bella, D. L., Hahn, C., and Stipanuk, M. H. 1999. Effects of nonsulfur and sulfur amino acids on the regulation of hepatic enzymes of cysteine metabolism. Am. J. Physiol. 277(1 Pt 1):E144–153.

    Google Scholar 

  69. Jerkins, A. A. and Steele, R. D. 1991. Cysteine sulfinic acid decarboxylase activity in response to thyroid hormone administration in rats. Arch. Biochem. Biophys. 286:428–432.

    Google Scholar 

  70. Bella, D. L., Hirschberger, L. L., Hosokawa, Y., and Stipanuk, M. H. 1999. Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo. Am. J. Physiol. 276(2 Pt 1):E326:335.

    Google Scholar 

  71. Jerkins, A. A., Jones, D. D., and Kohlhepp, E. A. 1998. Cysteine sulfinic acid decarboxylase mRNA abundance decreases in rats fed a high-protein diet. J. Nutr. 128(11):1890–1895.

    Google Scholar 

  72. Trenkner, E., Gargano, A., Scala, P., and Sturman, J. 1992. Taurine synthesis in cat and mouse in vivo and in vitro. Adv. Expt. Med. Biol. 315:7–14.

    Google Scholar 

  73. Bao, J., Cheung, W. Y., and Wu, J.-Y. 1995. Brain L-glutamate decarboxylase: Inhibition by phosphorylation and activation by dephosphorylation. J. Biol. Chem. 270:6464–6467.

    Google Scholar 

  74. Hsu, C.-C., Thomas, C., Chen, W., Davis, K. M., Foos, T., Chen, J. L., Wu, E., Floor, E., Schloss, J. V., and Wu, J.-Y. 1999. Role of synaptic vesicle proton gradient and protein phosphorylation on ATP-mediated activation of membrane associated brain glutamate decarboxylase. J. Biol. Chem. 274:24366–24371.

    Google Scholar 

  75. Hsu, C.-C., Davis, K. M., Jin, H., Foos, T., Floor, E., Chen, W., Tyburski, J. B., Yang, C.-Y., Schloss, J. V., and Wu, J.-Y. 2000. Association of L-glutamate decarboxylase to the 70–KDA heat shock protein as a potential anchoring mechanism to synaptic vesicles. J. Biol. Chem. 275:20822–20828.

    Google Scholar 

  76. Morales-Mulia, S., Morales-Mulia, S., Cardin V., Torres-Marquez M. E., Crevenna A., and Pasantes-Morales H. 2001. Influence of protein kinases on the osmosensitive release of taurine from cerebellar granule neurons. Neurochem. Int. 38(2):153–161.

    Google Scholar 

  77. Chen, W. Q., Jin, H., Nguyen, M., Carr, J., Lee, Y. J., Hsu, C. C., Faiman, M. D., Schloss, J. V., and Wu, J.-Y. Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons. J. Neurosci. Res. (In Press).

  78. Chen, W. Q., Jin, H., Nguyen, M., Carr, J., Lee, Y. J., Foos, T., Hsu, C. C., Davis, K. M., Schloss, J. V., and Wu, J.-Y. The neuroprotective role of taurine in cultured neurons. Chang-Hua Med. Journal (In Press).

  79. Wu, J.-Y., Chen, W. Q., Tang, X. W., Jin, H., Foos, T., Schloss, J. V., Davis, K. M., Faiman, M. D., and Hsu, C.-C. 2000. Mode of action of taurine and regulation dynamics of its synthesis in the CNS. Pages 35–44, in Della-Corte, L. and Huxtable, R. J. (eds.), Taurine and Excitable Tissues, Vol. 4, Plenum Press.

  80. Takuma, K., Matsuda, T., Hashimoto, H., Asano, S., and Baba, A., 1994. Cultured rat astrocytes possess Na+ - Ca2+ exchanger. Glia 12:336–342.

    Google Scholar 

  81. Hill, D. R., Bowery, N. G., and Hudson, A. L. 1984. Inhibition of GABAB receptor binding by guanyl nucleotides. J. Neurochem. 42:652–657.

    Google Scholar 

  82. Wu, J.-Y., Jin, H., Schloss, J. V., Faiman, M. D., Ningaraj, S. N., Foos, T., and Chen, W. 2001. Neurotoxic effect of acamprosate, n-acetyl-homotaurine, in cultured neurons. J. Biomed. Sci. 8(1):96–103.

    Google Scholar 

  83. Foos, T. and Wu J.-Y. Unpublished data.

  84. Lee, Y.-H., Deupree, D. L., Chen, S. C., Kao, L. S., and Wu, J.-Y. 1994. Role of Ca2+ in AMPA mediated poly phosphoinositides turnover in primary neuronal cultures. J. Neurochem. 62:2325–2332.

    Google Scholar 

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Foos, T.M., Wu, JY. The Role of Taurine in the Central Nervous System and the Modulation of Intracellular Calcium Homeostasis. Neurochem Res 27, 21–26 (2002). https://doi.org/10.1023/A:1014890219513

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