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Neurochemical Research

, Volume 24, Issue 2, pp 199–205 | Cite as

Sphingosylphosphorylcholine in Niemann-Pick Disease Brain: Accumulation in Type A But Not in Type B

  • Claire Rodriguez-Lafrasse
  • Marie T. Vanier
Article

Abstract

A study of brain lipids in patients with the sphingomyelinase-deficient types of Niemann-Pick disease demonstrated that abnormal accumulation of sphingomyelin occurs only in the brain of neuronopathic type A patients but not in the non-neuronopathic type B. Additional lipid abnormalities were present in the type A brain. In contrast, the brain lipid profile was normal in type B patients. Since lysosphingolipids have been implicated in the biochemical pathogenesis of other genetic lysosomal sphingolipidoses, the occurrence of Sphingosylphosphorylcholine (lysosphingomyelin) was specifically investigated in brain and extraneural tissues, using an HPLC method with fluorescent detection of orthophtalaldehyde derivatives. Levels close to or below the limit of detection (10 pmol/mg tissue protein) were observed in normal and pathological controls. A striking accumulation was observed in brain of two Niemann-Pick type A patients (830 and 430 pmol/mg protein in 27-and 16-month-old children with severe and milder neurological course, respectively), which was not present at the fetal stage of the disease. No significant increase was found in brain tissue from a 3.5 year-old type B patient. In liver and spleen, abnormally high Sphingosylphosphorylcholine levels were observed in both types of the disease, with indication of a progressive increase during development. This study establishes the integrity of brain tissue in Niemann-Pick disease type B and suggests that the lysocompound Sphingosylphosphorylcholine could play a role in the pathophysiology of brain dysfunction in the neuronopathic type A.

Niemann-Pick disease sphingomyelinase deficiency sphingosylphosphorylcholine lysosphingomyelin sphingomyelin 

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REFERENCES

  1. 1.
    Schuchman, E., and Desnick, R.J. 1995. Niemann-Pick disease types A and B: acid sphingomyelinase deficiencies. Pages 2601–2624, in C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (ed.) The Metabolic and Molecular Bases of Inherited Disease McGraw Hill: New York.Google Scholar
  2. 2.
    Vanier, M.T., and Suzuki, K. 1996. Niemann-Pick diseases. Pages 133–162, H.W. Moser, ed. Neurodystrophies and Neurolipidoses, Handbook of Clinical Neurology vol. 66, Elsevier Science: Amsterdam.Google Scholar
  3. 3.
    Kamoshita, A.S., Aron, A.M., Suzuki, K., and Suzuki, K. 1969. Infantile Niemann-Pick disease. A chemical study with isolation and characterization of membranous cytoplasmic bodies and myelin. Am. J. Dis. Child. 117: 379–394.PubMedGoogle Scholar
  4. 4.
    Brunngraber, E.G., Berra, B., and Zambotti, V. 1973. Altered levels of tissue glycoproteins, gangliosides, glycosaminoglycans and lipids in Niemann-Pick's disease. Clin. Chim. Acta 48: 173–181.PubMedGoogle Scholar
  5. 5.
    Vanier, M.T., Rousson, R., Zeitouni, R., Pentchev, P., and Louisot, P. 1986. Sphingomyelinase and Niemann-Pick disease. Pages 791–802, L Freysz, H. Dreyfus, R. Massarelli, S. Gatt, ed. Enzymes of Lipid Metabolism II, Plenum Press: New York.Google Scholar
  6. 6.
    Besley, G.T.N., and Elleder, M. 1986. Enzyme activities and phospholipid storage patterns in brain and spleen samples from Niemann-Pick disease variants: a comparison of neuropathic and non-neuropathic forms. J. Inherit. Metab. Dis. 9:59–71.PubMedGoogle Scholar
  7. 7.
    Vanier, M.T. and Svennerholm, L. 1975. Chemical pathology of Krabbe's disease: the occurrence of psychosine and other neutral sphingoglycolipids. Pages 115–126, B.W. Volk, L. Schneck, ed. Current Trends in Sphingolipidoses and Allied Disorders, New York: Plenum Press.Google Scholar
  8. 8.
    Svennerholm, L., Vanier, M.-T., and Månsson, J.-E. 1980. Krabbe disease: A galactosylsphingosine (psychosine) lipidosis. J. Lipid Res. 21:53–64.PubMedGoogle Scholar
  9. 9.
    Igisu, H., and Suzuki, K. 1984. Progressive accumulation of toxic metabolite in a genetic leukodystrophy. Science. 224:753–755.PubMedGoogle Scholar
  10. 10.
    Miyatake, T., and Suzuki, K. 1972. Globoid cell leukodystrophy: Additional deficiency of psychosine galactosidase. Biochem. Biophys. Res. Commun. 48:538–543.Google Scholar
  11. 11.
    Hannun, Y. A., and Bell, R. M. 1987. Lysosphingolipids inhibit protein kinase C: Implications for the sphingolipidoses. Science. 235:670–674.PubMedGoogle Scholar
  12. 12.
    Nilsson, O., and Svennerholm, L. 1982. Accumulation of glucosylceramide and glucosylsphingosine (psychosine) in cerebrum and cerebellum in infantile and juvenile Gaucher disease. J. Neurochem. 39:709–718.PubMedGoogle Scholar
  13. 13.
    Neuenhofer, S., Conzelmann, E., Schwarzmann, G., Egge, H., and Sandhoff, K. 1986. Occurrence of lysoganglioside lyso-GM2 (II3-Neu5Ac-gangliotriosylsphingosine) in GM2 gangliosidosis brain. Biol. Chem. Hoppe-Seyler. 367:241–244.PubMedGoogle Scholar
  14. 14.
    Rosengren, B., Månsson, J.-E., and Svennerholm, L. 1987. Composition of gangliosides and neutral glycosphingolipids of brain in classical Tay-Sachs and Sandhoff disease: More lyso-GM2 in Sandhoff disease? J. Neurochem. 49:834–840.PubMedGoogle Scholar
  15. 15.
    Kobayashi, T., Goto, I., Okada, S., Orii, T., Ohno, K., and Nakano, T. 1992. Accumulation of lysosphingolipids in tissues from patients with GM1 and GM2 gangliosidoses. J Neurochem. 59: 1452–1458.PubMedGoogle Scholar
  16. 16.
    Toda, K.-I., Kobayashi, T., Goto, I., Ohno, K., Eto, Y., Inui, K., and Okada, S. 1990. Lysosulfatide (sulfogalactosylsphingosine) accumulation in tissues from patients with metachromatic leukodystrophy. J Neurochem. 55:1585–1591.PubMedGoogle Scholar
  17. 17.
    Rosengren, B., Fredman, P., Månsson, J.-E., and Svennerholm, L. 1989. Lysosulfatide (galactosylsphingosine-3-O-sulfate) from metachromatic leukodystrophy and normal human brain. J. Neurochem. 1035–1041.Google Scholar
  18. 18.
    Strasberg, P.M., and Callahan, J.W. 1988. Psychosine and sphingosylphosphorylcholine bind to mitochondrial membranes and disrupt their function. Pages 601–606, R. Salvayre, L. Douste-Blazy, S. Gatt, (ed) Lipid Storage Disorders Plenum Press: New York.Google Scholar
  19. 19.
    Rodriguez-Lafrasse, C., and Vanier, M.T. 1993. Sphingosyl-phosphorylcholine in Niemann-Pick disease brain: Accumulation in type A but not in type B. J. Neurochem. 61(Suppl.): S101BGoogle Scholar
  20. 20.
    Landrieu, P., and Saïd, G. 1984. Peripheral neuropathy in type A Niemann-Pick disease. Acta Neuropathol. 63: 66–71PubMedGoogle Scholar
  21. 21.
    Labrune, P., Bedossa, P., Huguet, P., Roset, F., Vanier, M. T., and Odièvre, M. 1991. Fatal liver failure in two children with Niemann-Pick disease type B. J Ped. Gastroenter. Nutr. 13:104–109.Google Scholar
  22. 22.
    Vanier, M.T., Ferlinz, R., Rousson, R., Duthel, S., Louisot, P., Sandhoff, K., and Suzuki, K. 1993. Deletion of arginine (608) in acid sphingomyelinase is the prevalent mutation among Niemann-Pick disease type B patients from northern Africa. Hum. Genet. 92: 325–330.PubMedGoogle Scholar
  23. 23.
    Vanier, M.T., and Svennerholm, L. 1972. The distribution of lipids in the human nervous system. II-Lipid composition of human foetal and infant brain. Brain Res. 47: 457–468.PubMedGoogle Scholar
  24. 24.
    Martin, J.J., Lowenthal, A., Ceuterick, C., and Vanier, M. T. 1984. Juvenile dystonic lipidosis (variant of Niemann-Pick disease type C) J. Neurol. Sci. 66:33–45.PubMedGoogle Scholar
  25. 25.
    Kaller, H. 1961. Preparative isolation of sphingosylphosphorylcholine. Biochem. Z. 334: 451–456.PubMedGoogle Scholar
  26. 26.
    Merrill, A.H., Wang, E., Mullins, R.E., Jamison, W.C., Nimkar, S., and Liotta D.C. 1988. Quantitation of free sphingosine in liver by high-performance liquid chromatography. Anal. Biochem. 171:373–381.PubMedGoogle Scholar
  27. 27.
    Rodriguez-Lafrasse, C., Rousson, R., Pentchev, P.G., Louisot, P., and Vanier, M. T. 1994. Free sphingoid bases in tissues from patients with type C Niemann-Pick disease and other lysosomal storage disorders. Biochim. Biophys. Acta 1226: 138–144.PubMedGoogle Scholar
  28. 28.
    Vanier, M.T., Holm, M., Månsson, J.E., and Svennerholm, L. 1973. The distribution of lipids in the human nervous system-V. Gangliosides and allied neutral glycolipids of infant brain. J. Neurochem. 21: 1375–1384.PubMedGoogle Scholar
  29. 29.
    Pentchev, P.G., Vanier, M.T., Suzuki, K., and Patterson, M. 1995. Niemann-Pick disease type C: a cellular cholesterol lipidosis. Pages 2625–2639. In C. R. Scriver, A. L. Beaudet, W. S. Sly, D. Valle, (ed.) The Metabolic and Molecular Bases of Inherited Disease. McGraw Hill: New York.Google Scholar
  30. 30.
    Vanier, M. T., Rousson, R., Garcia, I., Bailloud, G., Juge, M. C., Revol, A., and Louisot, P. 1985. Biochemical studies in Niemann-Pick disease. III. In vitro and in vivo assays of sphingomyelin degradation in cultured skin fibroblasts and amniotic fluid cells for the diagnosis of the various forms of the disease. Clin. Genet. 27: 20–32.PubMedGoogle Scholar
  31. 31.
    Graber D., Salvayre, R., and Levade, T. 1994. Accurate differentiation of neuronopathic and nonneuronopathic forms of Niemann-Pick disease by evaluation of the effective residual lysosomal sphingomyelinase activity in intact cells. J. Neurochem. 63: 1060–1068.PubMedGoogle Scholar
  32. 32.
    Conzelmann, E., and Sandhoff, K. 1983. Partial enzyme deficiencies: residual activities and the development of neurological disorders. Dev. Neurosci. 6: 58–71.PubMedGoogle Scholar
  33. 33.
    Kobayashi, T., Goto, I., Yamanaka, T., Suzuki, Y., Nakano, T., and Suzuki, K. 1988. Infantile and fetal globoid cell leukodystrophy: analysis of galactosylceramide and galactosylsphingosine. Ann. Neurol. 24: 5217–522.Google Scholar
  34. 34.
    Matsumoto, A., Vanier, M.T., Oya, Y., Kelly, D., Popko, B., Wenger, D.A., Suzuki, K., and Suzuki, K. 1997. Transgenic introduction of human galactosylceramidase into twitcher mouse: significant phenotype improvement with a minimal expression. Dev. Brain Dysfunct., 10: 142–154.Google Scholar
  35. 35.
    Rodriguez-Lafrasse, C., Rousson, R., Valla, S., Antignac, P., Louisot, P., and Vanier, M. T. 1997. Modulation of protein kinase C by endogenous sphingosine: inhibition of phorbol dibutyrate binding in Niemann-Pick C fibroblasts. Biochem. J. 325: 787–791.PubMedGoogle Scholar
  36. 36.
    Horinouchi, K., Ehrlich, S., Perl, D. P., Ferlinz, K., Bisgaier, C. L., Sandhoff, K., Desnick, R. J., Stewart, C. L., and Schuchman, E. H. 1995. Acid sphingomyelinase-deficient mice: a model of types A and B Niemann-Pick disease. Nature Gen. 10: 288–293.Google Scholar
  37. 37.
    Suzuki, K. 1998. Twenty five years of the ≪psychosine hypothesis≫: a personal perspective of its history and present status. Neurochem. Res. 23: 251–259.PubMedGoogle Scholar
  38. 38.
    Fujino, Y., Negishi, T., and Ito, S. 1968. Enzymatic synthesis of sphingosylphosphorylcholine. Biochem. J. 109: 310–311.PubMedGoogle Scholar
  39. 39.
    Stoffel, W., and Melzner, I. 1980. Studies in vitro on the biosynthesis of ceramide and sphingomyelin: a reevaluation of proposed pathways. HoppeSeyler's Z. Physiol. Chem. 361: 755–771.Google Scholar
  40. 40.
    Marggraf, W. and Kanfer, J.N. 1984. The phosphorylcholine acceptor in the phosphatidylcholine: ceramide choline phosphotransferase reaction. Is the enzyme a transferase or a hydrolase. Biochim. Biophys. Acta 793: 346–353.PubMedGoogle Scholar
  41. 41.
    Futerman, A.H., Stieger, B., Hubbard, A.L., and Pagano, R. E. 1990. Sphingomyelin synthesis in rat liver occurs predominantly at the cis and medial cisternae of the Golgi apparatus. J. Biol. Chem. 265: 8650–8657.PubMedGoogle Scholar
  42. 42.
    Pentchev, P.G., Brady, R.O., Gal, A.E., and Hibbert, S. R. 1977. The isolation and characterization of sphingomyelinase from human placental tissue. Biochim. Biophys. Acta. 488: 312–321.PubMedGoogle Scholar
  43. 43.
    Yamanaka, T., and Suzuki, K. 1982. Acid sphingomyelinase of human brain: Purification to homogeneity. J. Neurochem. 38: 1753–1764.PubMedGoogle Scholar
  44. 44.
    Quintern, L.E., Weitz, G., Nehrkorn, H., Tager, J.M., Schram, A.W., and Sandhoff, K. 1987. Acid sphingomyelinase from human urine: purification and characterization. Biochim. Biophys. Acta 922: 323–326.PubMedGoogle Scholar
  45. 45.
    Callahan, J.W., Gerrie, J., Jones, C.S., and Shankaran, P. 1981. Studies on the hydrophobic properties of sphingomyelinase. Biochem. J. 193: 275–283.PubMedGoogle Scholar
  46. 46.
    Strasberg, P.M., and Callahan, J.W. 1988. Lysosphingolipids and mitochondrial function. II. Deleterious effects of sphingosylphosphorylcholine. Biochem. Cell Biol. 66: 1322–1332.PubMedGoogle Scholar
  47. 47.
    Sugiyama, E., Uemura, K.I., Hara, A., Taketomi, T. 1993. Metabolism and neurite promoting effect of exogenous sphingosylphosphorylcholine in cultured murine neuroblastoma cells. J. Biochem. 113: 467–472.PubMedGoogle Scholar
  48. 48.
    Desai, N., and Spiegel, S. 1991. Sphingosylphosphorylcholine is a remarkably potent mitogen for a variety of cell lines. Biochem. Biophys. Res. Commun. 181: 361–366.PubMedGoogle Scholar
  49. 49.
    Desai, N.N., Carlson, R.O., Mattie, M.E., Olivera, A., Buckley, N.E., Seki, T., Brooker, G., and Spiegel, S. 1993. Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts. J. Cell Biol. 121: 1385–1394.PubMedGoogle Scholar
  50. 50.
    Gosh, T.K., Bian, J., and Gill, D.H. 1990. Intracellular calcium release mediated by sphingosine derivatives generated in cells. Science 248: 1653–1656.PubMedGoogle Scholar
  51. 51.
    Berger, A., Rosenthal, D., and Spiegel, S. 1995. Sphingosylphosphorylcholine, a signaling molecule which accumulates in Niemann-Pick disease type A, stimulates DNA-binding activity of the transcription activator protein AP-1. Proc. Natl. Acad. Sci. USA 92: 5885–5889.PubMedGoogle Scholar
  52. 52.
    Berger, A., Cultaro, C.M., Segal, S., and Spiegel, S., 1998. The potent lipid mitogen sphingosylphosphocholine activates the DNA binding activity of upstream stimulating factor (USF), a basic helix-loop-helix-zipper protein. Biochim. Biophys. Acta 1390: 225–236.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Claire Rodriguez-Lafrasse
    • 1
  • Marie T. Vanier
    • 1
    • 2
  1. 1.Department of BiochemistryLyon-Sud School of MedicineOullinsFrance
  2. 2.Laboratoire de Neurochimie Fondation Gillet-MerieuxCentre Hospitalier Lyon-SudPierre BeniteFrance

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