Cellular and Molecular Neurobiology

, Volume 21, Issue 1, pp 1–13 | Cite as

Intracellular Calcium Changes in Neuronal Cells Induced by Alzheimer's ß-Amyloid Protein Are Blocked by Estradiol and Cholesterol

  • Masahiro Kawahara
  • Yoichiro Kuroda
Article

Abstract

1. The elevation of intracellular Ca2+ levels ([Ca2+]i) in immortalized hypothalamic neurons (GT1–7 cells) after exposure to Alzheimer's ß-amyloid protein (AßP[25–35]) was investigated using a multisite fluorometry system.

2. The marked rise in [Ca2+]i appeared afterexposure to 5–20-μM AßP[25–35]. Analysis of the spatiotemporal patterns of [Ca2+]i changes revealed that the magnitude and the latency of the response to AßP in each cell werehighly heterogeneous.

3. The preadministration of 17ß-estradiol, 17α-estradiol, phloretin and cholesterol, which influence the properties of membranes, such as membrane fluidity or membrane potential, significantly decreased the rise in [Ca2+]i.

4. These findings support the idea that disruption of calcium homeostasis by AßP channels may be the molecular basis of the neurotoxicity of AßP and of the pathogenesis of Alzheimer's disease. It is also suggested that membrane properties may play key roles in the expression of neurotoxicity.

amyloid ion channel membrane lipids cholesterol estradiol 

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REFERENCES

  1. Arispe, N., Rojas, E., and Pollard, H. B. (1993a). Alzheimer disease amyloid β protein forms calcium channels in bilayer membranes: Blockade by tromethamine and aluminum. Proc. Natl. Acad. Sci. U.S.A. 90:567-571.Google Scholar
  2. Arispe, N., Rojas, E., and Pollard, H. B. (1993b). Giant multilevel cation channels formed by Alzheimer disease amyloid β protein [AβP-(1–40)] in bilayer membranes. Proc. Natl. Acad. Sci. U.S.A. 90:10573-10577.Google Scholar
  3. Arispe, N., Pollard, H. B., and Rojas, E. (1996). Zn2+ interactions with Alzheimer's amyloid β protein calcium channels. Proc. Natl. Acad. Sci. U.S.A. 93:1710-1715.Google Scholar
  4. Bechinger, B. (1997). Structure and functions of channel-forming peptides: Magainins, cecropins, melittin and alamethicin. J. Membr. Biol. 156:197-211.Google Scholar
  5. Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., and Pericak-Vance, M. A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261:921-923.Google Scholar
  6. Costa, M. M., Reus, V. I., Wolkowitz, O. M., Manfredi, F., and Lieberman, M. (1999). Estrogen replacement therapy and cognitive decline in memory-impaired post-menopausal women. Biol. Psychiatry 46:182-188.Google Scholar
  7. Durell, S. R., Guy, H. R., Arispe, N., Rojas, E., and Pollard, H. B. (1994). Theoretical models of the ion channel structure of amyloid β-protein. Biophys. J. 67:2137-3145.Google Scholar
  8. Fraser, S. P., Suh, Y. H., Chong, Y. H., and Djamgoz, M. B. (1996). Membrane currents induced in Xenopus oocytes by the C-terminal fragment of the β-amyloid precursor protein. J. Neurochem. 66:2034-2040.Google Scholar
  9. Fujii, G., Chang, J. E., Coley, T., and Steere, B. (1997). The formation of amphotericin B ion channels in lipid bilayers. Biochemistry 36:4959-4968.Google Scholar
  10. Furukawa, K., Abe, Y., and Akaike, N. (1994). Amyloid β protein-induced irreversible current in rat cortical neurones. Neuroreport 27:2016-2018.Google Scholar
  11. Green, P. S., Gridley, K. E., and Simpkins, J. W. (1996). Estradiol protects against β-amyloid (25–35)-induced toxicity in SK-N-SH human neuroblastoma cells. Neurosci. Lett. 218:165-168.Google Scholar
  12. Haass, C., and Selkoe, D. J. (1993). Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide. Cell 75:1039-1042.Google Scholar
  13. Hardy, J. A., and Higgins, J. A. (1992). Alzheimer's disease: The amyloid cascade hypothesis. Science 256:780-783.Google Scholar
  14. Hertel, C., Terzi, E., Hauser, N., Jakob-Rotne, R., Seelig, J., and Kemp, J. A. (1997). Inhibition of the electrostatic interaction between β-amyloid peptide and membranes prevents beta-amyloid-induced toxicity. Proc. Natl. Acad. Sci. U.S.A. 94:9412-9416.Google Scholar
  15. Hirakura, Y., Lin, M. C., and Kagan, B. L. (1999). Alzheimer amyloid Aβ1-42 channels: Effects of solvent, pH, and Congo Red. J. Neurosci. Res. 57:458-466.Google Scholar
  16. Kawahara, M., Arispe, N., Kuroda, Y., and Rojas, E. (1997). Alzheimer's disease amyloid β-protein forms Zn2+-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons. Biophys. J. 73:67-75.Google Scholar
  17. Kawahara, M., Arispe, N., Kuroda, Y., and Rojas, E. (2000). Alzheimer's β-amyloid, human islet amylin and prion protein fragment evoke intracellular free-calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell-line. J. Biol. Chem. 275:14077-14083.Google Scholar
  18. Kuiper, G. G., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., van der Burg, B., and Gustafsson, J. A. (1998). Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139:4252-63.Google Scholar
  19. Lin, J. H., and Baumgaertner, A. (2000). Stability of a melittin pore in a lipid bilayer: A molecular dynamics study. Biophys. J. 78:1714-24.Google Scholar
  20. Lundbaek, J. A., Birn, P., Girshman, J., Hansen, A. J., and Anderson, O. S. (1996). Membrane stiffness and channel function. Biochemistry 35: 3825-3830.Google Scholar
  21. Matsuzaki, K., Murase, O., Fujii, N., and Miyajima, K. (1996). An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry 35:11361-11368.Google Scholar
  22. Mellon, P. L., Windle, J. J., Goldsmith, P. C., Padula, J. L., and Weiner, R. I. (1990). Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis Neuron 5:1-10.Google Scholar
  23. Mirzabekov, T. A., Lin, M. C., and Kagan, B. L. (1996). Pore formation by the cytotoxic islet amyloid peptide amylin. J. Biol. Chem. 271:1988-1992.Google Scholar
  24. Mirzabekov, T., Lin, M. C., Yuan, W. L., Marshall, P. J., Carman, M., Tomaselli, K., Lieberburg, I., and Kagan, B. L. (1994). Channel formation in planar lipid bilayers by a neurotoxic fragment of the β-amyloid peptide. Biochem. Biophys. Res. Commun. 202:1142-1148.Google Scholar
  25. Ogura, A., Iijima, T., Amano, T., and Kudo, Y. (1987). Optical monitoring of excitatory synaptic activity between cultured hippocampal neurons by a multi-site Ca2+ fluorometry. Neurosci. Lett. 78:69-74.Google Scholar
  26. Rokitskaya, T. I., Antonenko, Y. N., and Kotova, E. A. (1997). Effect of the dipole potential of a bilayer lipid membrane on gramicidin channel dissociation kinetics. Biophys. J. 73:850-854.Google Scholar
  27. Schwartz, Z., Gates, P. A., Nasatzky, E., Sylvia, V. L., Mendez, J., Dean, D. D., and Boyan, B. D. (1996). Effect of 17 β-estradiol on chondrocyte membrane fluidity and phospholipid metabolism is membrane-specific, sex-specific, and cell maturation-dependent. Biochem. Biophys. Acta 13:1-10.Google Scholar
  28. Seelig, J., Lehrmann, R., and Terzi, E. (1995). Domain formation induced by lipid-ion and lipid-peptide interactions. Mol. Membr. Biol. 12:51-57.Google Scholar
  29. Selkoe, D. J. (1991). The molecular pathology of Alzheimer disease. Neuron 6:487-498.Google Scholar
  30. Simmons, M. A., and Schneider, C. R. (1993). Amyloid β peptides act directly on single neurons. Neurosci. Lett. 150:133-136.Google Scholar
  31. Spergel, D. J., Catt, K. J., and Rojas, E. (1996). Immortalized GnRH neurons express large-conductance calcium-activated potassium channels. Neuroendocrinology 63:101-111.Google Scholar
  32. Yankner, B. A., Duffy, L. K., and Kirschner, D. A. (1990). Neurotropic and neurotoxic effects of amyloid β protein: Reversal by tachykinin neuropeptides Nature 250:279-282.Google Scholar
  33. Zhou, Y., and Richardson, J. S. (1996). Cholesterol protects PC12 cells from β-amyloid induced calcium disordering and cytotoxicity. Neuroreport 7:2487-2490.Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Masahiro Kawahara
    • 1
  • Yoichiro Kuroda
    • 1
  1. 1.Department of Molecular & Cellular NeurobiologyTokyo Metropolitan Institute for NeuroscienceTokyoJapan

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