Abstract
Previous studies have demonstrated that in glia and astrocytes Mn(II) is distributed with ca. 30–40% in the cytoplasm, 60–70% in mitochondria. Ca(II) ions were observed to alter both the flux rates and distribution of Mn(II) ions in primary cultues of chick glia and rat astrocytes. External (influxing) Ca(II) ions had the greatest effect on Mn(II) uptake and efflux, compared to internal (effluxing) or internal-external equilibrated Ca(II) ions. External (influxing) Ca(II) ions inhibited the net rate and extent of Mn(II) uptake but enhanced Mn(II) efflux from mitochondria. These observations differ from Ca(II)−Mn(II) effects previously reported with “brain” (neuronal) mitochondria. Overall, increased cytoplasmic Ca(II) acts to block Mn(II) uptake and enhance Mn(II) release by mitochondria, which serve to increase the cytoplasmic concentration of free Mn(II). A hypothesis is presented involving external L-glutamate acting through membrane receptors to mobilize cell Ca(II), which in turn causes mitochondrial Mn(II) to be released. Because the concentration of free cytoplasmic Mn(II) is poised near the Kd for Mn(II) with glutamine synthetase, a slight increase in cytoplasmic Mn(II) will directly enhance the activity of glutamine synthetase, which catalyzes removal of neurotoxic glutamate and ammonia.
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References
Metal Ions in Neurology and Psychiatry, Gabay, S., Harris, J., and Ho, B. T. (eds.) pp. 3–34, 49–68, 121–128, Liss, New York, 1985.
Underwood, E. J. 1977. Trace Elements in Human and Animal Nutrition. 4th Edn. pp. 171–195, Academic Press, New York.
Manganese in Metabolism and Enzyme Function, Schramm, V. L., and Wedler, F. C. (eds.) Academic Press, New York, 1986.
Gianutsos, G., Seltzer, M. D., Saymeh, R., Wu, M. W., and Michel, R. G. 1985. Brain manganese accumulation following systemic administration of different forms. Arch. Toxicol. 57:272–275.
Wedler, F. C., Ley, B. W., and Grippo, A. A. 1989. Manganese(II) dynamics and distribution in glial cells cultured from chick cerebral cortex. Neurochem. Res. 14:1129–1135.
Aschner, M., Gannon, M., and Kimelberg, H. K. 1992. Manganese uptake and efflux in cultured rat astrocytes. J. Neurochem. 58:730–735.
Tholey, G., Ledig, M., Kopp, P., Sargentini-Maier, L., Leroy, M., Grippo, A. A., and Wedler, F. C. 1988. Levels and subcellular distribution of physiologically important metal ions in neuronal cells cultured from chick embryo cerebral cortex. Neurochem. Res. 13:1163–1167.
Tholey, G., Ledig, M., Mandel, P., Sargentini, L., Frivold, A. H., Leroy, M., Grippo, A. A., and Wedler, F. C. 1988. Concentrations of physiologically important metal ions in glial cells cultured from chick cerebral cortex. Neurochem. Res. 13:45–50.
Schramm, V. L. 1986. Evaluation of Mn(II) in metabolic regulation: analysis of proposed sites for regulation,in ref., pp. 109–132.
Scrutton, M. C. 1986. Manganese and pyruvate carboxylase,in ref., pp. 147–163.
Nowak, T. 1986. Manganese and phosphoenolpyruvate carboxykinase,in ref., pp. 165–191.
Beyer, W. F., Jr., and Fridovich, I. 1986. Manganese-catalase and manganese superoxide dismutase: spectroscopic similarity with functional diversity.in ref., pp. 193–219.
Wedler, F. C., and Toms, R. 1986. Interactions of Mn(II) with mammalian glutamine synthetase.in ref., pp. 221–238.
Maurizi, M. R., Pinkofsky, H. B., and Ginsberg, A. 1987. ADP, chloride ion, and metal ion binding to bovine brain glutamine synthetase. Biochemistry 26:5023–5031.
Wedler, F. C., and Ley, B. W. 1994. Kinetic, ESR, and trapping evidence for in vivo binding of Mn(II) to glutamine synthetase in brain cells. Neurochem. Res. 19:139–144 (accompanying paper).
Meister, A. 1980. Catalytic mechanisms of glutamine synthetase: overview of glutamine metabolism.in Glutamine: Metabolism, Enzymology, and Regulation, Mora, J., and Palacios, R. (eds.), pp. 1–40, Academic Press, New York.
Sensenbrenner, M. 1977. Dissociated brain cells in primary culture, pp. 191–213,in Federoff, S., and Hertz, L. (eds.), Cell, Tissue, and Organ Culture in Neurobiology, Academic Press, New York.
Bottenstein, J. E., and Sato, G. H. 1979. Growth of a neuroblastoma cell line in serum-free supplemented medium. Proc. Nat. Acad. Sci, USA 76:514–517.
Frangakis, M. V., and Kimelberg, H. K. 1984. Dissociation of neonatal rat brain by Dispase for preparation of primary astrocyte cultures. Neurochem. Res. 9:1689–1698.
Goldschmidt, R. C., and Kimelberg, H. K. 1989. Protein analysis of mammalian cells in monolayer culture using the bicinchononic assay. Anal. Biochem. 176:41–45.
Tholey, G., Megias-Megias, L., Wedler, F. C., and Ledig, M. 1990. Modulation of Mn2+ accumulation in cultured rat neuronal and astroglial cells. Neurochem. Res. 7:751–754.
Blankenfeld, G. V., and Kettenmann, H. 1992. Glutamate and GABA receptors in vertebrate glial cells. Molec. Neurobiol. 5:31–43.
Ahmed, Z., Lewis, C. A., and Faber, D. S. 1990. Glutamate stimulates release of Ca2+ from internal stores in astroglia. Brain Res. 516:165–169.
Konji, V., Montag, A., Sandri, G., Nordenbrand, K., and Ernster, L. 1985. Transport of Ca2+ and Mn2+ by mitochondria from rat liver, heart, and brain. Biochimie 67:1241–1250.
Gavin, C. E., Gunter, K. K., and Gunter, T. E. 1990. Manganese and calcium efflux kinetics in brain mitochondria: relevance to manganese toxicity. Biochem. J. 266:329–334.
Allshire, A., Bernardi, P., and Saris, N-E. L. 1985. Manganese stimulates calcium flux through the mitochondrial uniporter. Biochim. Biophys. Acta 807:202–209.
Shamoo, A. E. 1986. Mn(II) and Ca(II) transport in mitochondria,in ref., pp. 51–64.
Li, X., Song, L., and Jope, R. 1990. Modulation of phosphoinositide metabolism in rat brain slices by excitory amino acids, arachidonic acid, and GABA. Neurochem. Res. 15:725–738.
Goldman, R. S., Chavez-Noriega, L. E., and Stevens, C. F. 1990. Failure to reverse long-term potentiation by coupling sustained presynaptic activity and N-methyl-D-aspartate receptor blockade. Proc. Nat. Acad. Sci., US 87:7165–7169.
Rosenberg, P. A. 1991. Accumulation of extracellular glutamate and neuronal death in astrocyte-poor cortical cultures exposed to glutamine. Glia 4:91–100.
Walker, J. E. 1983. Glutamate, GABA, and CNS disease: a review. Neurochem. Res. 8:521–548.
Shank, R. P., and Campbell, G. LeM. 1983. Glutamate.in Handbook of Neurochemistry (Lajtha, A., ed.) vol. 3 (2nd Edn.) Plenum, New York, pp. 381–404.
Greenmayre, J. T. 1986. The role of glutamate in neurotransmission and in neurologic disease. Neurol. Rev. 43:1058–1063.
Sahai, S. 1990. Glutamate in the mammalian CNS. Eur. Arch. Psych. Clin. Neurosci. 240:121–133.
Baudry, M., and Lynch, G. 1979. Regulation of glutamate receptors by cations. Nature 282:748–750.
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Wedler, F.C., Vichnin, M.C., Ley, B.W. et al. Effects of Ca(II) ions on Mn(II) dynamics in chick glia and rat astrocytes: Potential regulation of glutamine synthetase. Neurochem Res 19, 145–151 (1994). https://doi.org/10.1007/BF00966809
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DOI: https://doi.org/10.1007/BF00966809