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Release of intracellular calcium stores leads to retraction of membrane sheets and cell death in mature mouse oligodendrocytes

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Abstract

The ability of mature oligodendrocytes (OLs) to recover from insult is important in repair of damage following demyelination. Since regulation of Ca2+ levels within cells plays a critical role in function and survival, this study investigates the effects of changes in cytoplasmic Ca2+ on the viability of cultured mouse OLs and their ability to maintain membrane sheets. Mature OLs in culture respond rapidly to the calcium ionophore A23187 and promptly return to resting Ca2+ levels when the ionophore is removed. Longer exposure to 0.1–1.0 μM A23187 leads to microtubule disruption, membrane sheet retraction and eventual cell death; nuclear lysis occurs in many of the OLs, as reported by Scolding, et al. (1) for rat OLs. In our cultures, mature OLs were more susceptible to nuclear lysis than were immature OLs or astroglia. Release of intracellular Ca2+ stores with thapsigargin at 5–10 μM also leads to retraction of membrane sheets. Following 6 hours of continuous exposure to thapsigargin, the effects on membrane sheets are reversed over the next 12 hours. After 18 hours of continuous exposure to thapsigargin, only occasional nuclear lysis is observed, but a number of the mature OLs show signs of DNA fragmentation, indicating that apoptotic death is occurring. Our results suggest that mature OLs cannot survive a prolonged influx of extracellular calcium as readily as immature OLs and astroglia, but have mechanisms to withstand similar increases in cytoplasmic Ca2+ following sustained release of intracellular stores.

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References

  1. Scolding, N. J., Morgan, B. P., Campbell, A. K., and Compston, D. A. S. 1990. The role of calcium in rat oligodendrocyte injury and repair. Neurosci. Lett. 135:95–98.

    Article  Google Scholar 

  2. Smith, M. E. 1968. The turnover of myelin in the adult rat, Biochim. Biophys. Acta 164:285.

    PubMed  CAS  Google Scholar 

  3. Smith, M. E. 1980. Biosynthesis of peripheral nervous system myelin proteins in vitro. J. Neurochem. 35:1183.

    Article  PubMed  CAS  Google Scholar 

  4. Smith, M. E., and Eng, L. 1965. The turnover of the lipid components of myelin. J. Am. Oil. Chem. Soc. 42:1013.

    PubMed  CAS  Google Scholar 

  5. Benjamins, J. A., and Smith, M. E. 1984. Metabolism of Myelin. Pages 225–258,in P. Morell, (ed.), Myelin (2nd edition). Plenum Press, New York.

    Google Scholar 

  6. Smith, M. E., and Benjamins, J. A. 1984. Model systems for study of perturbations of myelin metabolism. Pages 441–487,in P. Morell, (ed.), Myelin (2nd edition). Plenum Press, New York.

    Google Scholar 

  7. Dyer, C. A., and Benjamins, J. A. 1988. Antibody to galactocerebroside alters organization of oligodendroglial membrane sheets in culture. J. Neurosci. 8:4307–4318.

    PubMed  CAS  Google Scholar 

  8. Knapp, P. E., Bartlett, W. P., and Skoff, R. P. 1987. Cultured oligodendrocytes mimic in vivo phenotypic characteristics: cell shape, expression of myelin-specific antigens, and membrane production. Developmental Biology 120:356–365.

    Article  PubMed  CAS  Google Scholar 

  9. Wilson, R., and Brophy, P. J. 1989. Role for the oligodendrocyte cytoskeleton in myelination. J. Neurosci. Res. 22:439–448.

    Article  PubMed  CAS  Google Scholar 

  10. Dyer, C. A., and Benjamins, J. A. 1990. Glycolipids and transmembrane signaling: Antibodies to galactocerebroside cause an influx of calcium in oligodendrocytes. J. Cell Biol. 111:625–633.

    Article  PubMed  CAS  Google Scholar 

  11. Benjamins, J. A., and Nedelkoska, L. 1994. Maintenance of membrane sheets by cultured oligodendrocytes requires continuous microtubule turnover and golgi transport. Neurochem. Res. 19:631–639.

    Article  PubMed  CAS  Google Scholar 

  12. Scolding, N. J., Houston, W. A. J., Morgan, B. P., Campbell, A. K., and Compston, D. A. S. 1989. Reversible injury of cultured rat oligodendrocytes by complement. Immunology 67:441–446.

    PubMed  CAS  Google Scholar 

  13. Jones, J., Frith, S., Piddlesden, S., Morgan, B. P., Compston, D. A. S., Campbell, A. K., Hallett, M. B. 1991. Imaging Ca2+ changes in individual oligodendrocytes attacked by T-cell perforin. Immunology 74:572–577.

    PubMed  CAS  Google Scholar 

  14. Shirazi, Y., Rus, H. G., Macklin, W. B., and Shin, M. L. 1993. Enhanced degradation of messenger RNA encoding myelin proteins by terminal complement complexes in oligodendrocytes. J. Immunol. 150:4581–4590.

    PubMed  CAS  Google Scholar 

  15. McCarthy, K. D., and Devellis, J. 1980. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 85:890–902.

    Article  PubMed  CAS  Google Scholar 

  16. Bottenstein, J. E. 1986. Growth requirements in vitro of oligodendrocyte cell lines and neonatal rat brain oligodendrocytes. Proc. Natl. Acad. Sci. USA 83:1955–1959.

    Article  PubMed  CAS  Google Scholar 

  17. Deber, C. M., et al. 1985. Bromo-A23187: a nonfluorescent calcium ionophore for use with fluorescent probes. Anal. Biochem. 146:349–352.

    Article  PubMed  CAS  Google Scholar 

  18. Thastrup, O., Cullen, P. J., Drobak, B. K., Hanley, M. R., and Dawson, A. P. 1990. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc. Natl. Acad. Sci. USA 87:2466–2470.

    Article  PubMed  CAS  Google Scholar 

  19. Thastrup, O., Dawson, A. P., Scharff, O., Foder, B., Cullen, P. J., Drobak, B. K., Bjerrum, P. J., Christensen, S. B., and Hanley, M. R. 1989. Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage. Agents and Actions 27: 17–23.

    Article  PubMed  CAS  Google Scholar 

  20. Schachner, M, Kim, S. K., and Zehnle, R. 1981. Developmental expression in central and peripheral nervous system of oligodendrocyte cell surface antigens (O antigens) recognized by monoclonal antibodies. Developmental Biology 83:328–338.

    Article  PubMed  CAS  Google Scholar 

  21. Sommer, I., and Schachner, M. 1981. Monoclonal antibodies (O1−O4) to oligodendrocyte cell surfaces: An immunocytological study in the central nervous system. Dev. Biol. 83:311–327.

    Article  PubMed  CAS  Google Scholar 

  22. Sommer, I., and Schachner, M. 1982. Cells that are O4 antigen positive and O1-antigen negative differentiate into O1 antigenpositive oligodendrocytes. Neurosci. Lett. 29:183–188.

    Article  PubMed  CAS  Google Scholar 

  23. Bansal, R., Stefansson, K., and Pfeiffer, S. E. 1992. Proligodendroblast antigen (POA), a developmental antigen expressed by A007/O4-positive oligodendrocyte progenitors prior to the appearance of sulfatide and glactocerebroside. J. Neurochem. 58: 2221–2229.

    Article  PubMed  CAS  Google Scholar 

  24. Bansal, R., Warrington, A. E., Gard, A. L., Ranscht, B., and Pfeiffer, S. E. 1989. Multiple and novel specificities of monoclonal antibodies O1, O4 and R-mAb used in the analysis of oligodendrocyte development. J. Neurosci. Res. 24:548–557.

    Article  PubMed  CAS  Google Scholar 

  25. Virtanen, I., Ekblom, P., and Laurila, P. 1980. Subcellular compartmentalization of saccharide moieties in cultured normal and malignant cells. J. Cell Biol. 85:429–434.

    Article  PubMed  CAS  Google Scholar 

  26. Tartakoff, A. M., and Vassalli, P. 1983. Lectin-binding sites as markers of Golgi sub compartment: Proximal-to-distal maturation of oligosaccharides. J. Cell Biol. 97:1243–1248.

    Article  PubMed  CAS  Google Scholar 

  27. Dyer, C. A., and Benjamins, J. A. 1991. Galactocerebroside and sulfatide independently mediate Ca2+ responses in oligodendrocytes. J. Neurosci. Res. 30:699–711.

    Article  PubMed  CAS  Google Scholar 

  28. Wing, M. G., Zajicek, J., Seilly, D. J., Compston, D. A. S., and Lachmann, P. J. 1992. Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59. Immunology 76: 140–145.

    PubMed  CAS  Google Scholar 

  29. Blankenfeld, G. V., Verkhratsky, A. N., and Kettenmann, H. 1992. Ca2+ channel expression in the oligodendrocyte lineage. Eur. J. Neurosci. 4:1035–1048.

    Article  Google Scholar 

  30. Sontheimer, H., Trotter, M., Schachner, M., and Kettenmann, H. 1989. Channel expression correlates with differentiation stage during the development of oligodendrocytes from their precursor cells in culture. Neuron 2:1135–1145.

    Article  PubMed  CAS  Google Scholar 

  31. Wood, A., Wing, M. G., Benham, C. D., and Compston, D. A. S. 1993. Specific induction of intracellular calcium oscillations by complement membrane attack on oligodendroglia. J. Neurosci. 13: 3319–3332.

    PubMed  CAS  Google Scholar 

  32. Smith, K. J., and Hall, S. M. 1994. Central demyelination induced in vivo by the calcium ionophore ionomycin. Brain 117:1351–1356.

    PubMed  Google Scholar 

  33. Takeda, M., Nelson, D. J., and Soliven, B. 1995. Calcium signaling in cultured rat oligodendrocytes. Glia 14:225–236.

    Article  PubMed  CAS  Google Scholar 

  34. Berger, T., Schnitzer, J., Orkand, P. M., and Kettenmann, H. 1992. Sodium and calcium currents in glial cells of the mouse corpus callosum slices. Eur. J. Neurosci. 4:1277–1284.

    Article  Google Scholar 

  35. Levick, V., Coffey, H., and D’Mello, S. R. 1995. Opposing effects of thapsigargin on the survival of developing cerebellar granule neurons in culture. Brain Res. 676:325–335.

    Article  PubMed  CAS  Google Scholar 

  36. Kirischuk, S., Scherer, J., Kettenmann, H., and Verkhratsky, A. 1995. Activation of P2-purinoreceptors triggered Ca2+ release from InsP3-sensitive internal stores in mammalian oligodendrocytes. J. Physiol. 483:41–57.

    PubMed  CAS  Google Scholar 

  37. Pende, M., Holtzclaw, L. A., Curtis, J. L., Russell, J. T., Gallo, V. 1994. Glutamate regulates intracellular calcium and gene expression in oligodendrocyte progenitors through the activation of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Proc. Natl. Acad. Sci. USA 91:3215–3219.

    Article  PubMed  CAS  Google Scholar 

  38. Engle, J., Althaus, H. H., and Kristjansson, G. I. 1994. NGF increases [Ca2+]i in regenerating mature oligodendroglial cells. Neurochemistry 5:397–400.

    Google Scholar 

  39. Sanders, S. L., Whitfield, K. M., Vogel, J. P., Rose, M. D., and Schekman, R. W. 1992. Sec61p and BiP directly facilitate polypeptide translocation into the ER. Cell 69:353–365.

    Article  PubMed  CAS  Google Scholar 

  40. Hendershot, L. M. 1990. Immunoglobulin heavy chain and binding protein complexes are dissociated in vivo by light chain addition. J. Cell Biol. 111:829–837.

    Article  PubMed  CAS  Google Scholar 

  41. Resendez Jr., E., Ting, J., Kim, K. S., Wooden, S. K., and Lee, A. S. 1986. Calcium ionophore A23187 as a regulator of gene expression in mammalian cells. J. Cell Biol. 103:2145–2152.

    Article  PubMed  CAS  Google Scholar 

  42. Drummond, I. A. S., Lee, A. S., Resendez Jr., E., and Steubgardt, R. A. 1987. Depletion of intracellular calcium stores by calcium ionophore A23187 induces the genes for glucose-regulated proteins in hamster fibroblasts. J. Biol. Chem. 262:12801–12805.

    PubMed  CAS  Google Scholar 

  43. Li, W. W., Alexandre, S., Cao, X., and Lee, A. S. 1993. Transactivation of the grp78 promoter by Ca2+ depletion. J. Biol. Chem. 268:12003–12009.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Wayne State University School of Medicine, 421 E. Canfield Avenue, Detroit, MI, 48201

    Joyce A. Benjamins & Liljana Nedelkoska

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  1. Joyce A. Benjamins
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  2. Liljana Nedelkoska
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Special issue dedicated to Dr. Marion E. Smith.

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Benjamins, J.A., Nedelkoska, L. Release of intracellular calcium stores leads to retraction of membrane sheets and cell death in mature mouse oligodendrocytes. Neurochem Res 21, 471–479 (1996). https://doi.org/10.1007/BF02527712

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