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A Correlative Study on Amyloid β-Induced Cell Death Independent of Caspase Activation

  • Tuyet, Pham Thi Dieu (Department of Biotechnology, Hanoi University of Science and Technology, University of Hanoi)
  • Received : 2014.06.02
  • Accepted : 2014.06.25
  • Published : 2014.06.30

Abstract

Amyloid beta ($A{\beta}$) peptide has been implicated in the pathogenesis of Alzheimer's disease and has been reported to induce apoptotic death in cell culture. Cysteine Proteases, a family of enzymes known as caspases, mediate cell death in many models of apoptosis. In the present study, we examined the caspase activity and cell death in $A{\beta}$-treated SHSY5Y cells, as an attempt to elucidate the relationship between the type of caspase and $A{\beta}$-induced cell death. $A{\beta}$ at 20 ${\mu}M$ induce activation of caspase-3, 8 and 9 activity, but not the caspase-1. Caspase-3, 8 and 9 were processed by Ab treatment, consistent with the activity assay. Inhibition of the caspase activities by the selective inhibitors, however, marginally affected the cell death induced by $A{\beta}$. Taken together, the results indicate that $A{\beta}$-induced cell death may be independent of caspase activity and rather, the enzymes might be activated as a result of the cell death.

Keywords

References

  1. J. Hardy and D. J. Selkoe, "The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics", Science, Vol. 297, pp. 353-356, 2002. https://doi.org/10.1126/science.1072994
  2. D. T. Loo, A. Copani, C. J. Pike, E. R. Whittemore, A. J. Walencewicz, and C. W. Cotman, "Apoptosis is induced by $\beta$-amyloid in cultured central nervous system neurons", Proc. Natl. Acad. Sci. USA, Vol. 90, pp. 7951-7955, 1993. https://doi.org/10.1073/pnas.90.17.7951
  3. A. Copani, V. Bruno, G. Battaglia, G. Leanza, R. Pellitteri, A. Russo, S. Stanzani, and F. Nicoletti, "Activation of metabotropic glutamate receptors protects cultured neurons against apoptosis induced by $\beta$-amyloid peptide", Mol. Pharmacol., Vol. 47, pp. 890-897, 1995.
  4. K. J. Ivins, E. T. N. Bui, and C. W. Cotman, "$\beta$-Amyloid induces local neurite degeneration in cultured hippocampal neurons: evidence for neuritic apoptosis", Neurobiol. Dis., Vol. 5, pp. 365-378, 1998. https://doi.org/10.1006/nbdi.1998.0228
  5. J. Yuan and H. R. Horvitz, "A first insight into the molecular mechanisms of apoptosis", Cell, Vol. 116, pp. 53-56, 2004. https://doi.org/10.1016/S0092-8674(04)00028-5
  6. E. Masliah, M. Mallory, M. Alford, S. Tanaka, and L. A. Hansen, "Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer disease", J. Neuropathol. Exp. Neurol., Vol. 57, pp. 1041-1052, 1998. https://doi.org/10.1097/00005072-199811000-00007
  7. J. W. Allen, B. A. Eldadah, X. Huang, S. M. Knoblach, and A. I. Faden, "Multiple caspases are involved in $\beta$-amyloid induced neuronal apoptosis", J. Neurosci. Res., Vol. 65, pp. 45-53, 2001. https://doi.org/10.1002/jnr.1126
  8. C. Stadelmann, W. Bruck, C. Bancher, K. Jellinger, and H. Lassmann, "Alzheimer disease: DNA fragmentation indicates increased neuronal vulnerability, but not apoptosis", J. Neuropathol. Exp. Neurol., Vol. 57, pp. 456-464, 1998. https://doi.org/10.1097/00005072-199805000-00009
  9. J. Xiang, D. T. Chao, and S. J. Korsmeyer, "Baxinduced cell death may not require interleukin 1$\beta$-converting enzyme-like proteases", Proc. Natl. Acad. Sci. USA, Vol. 93, pp. 14559-14563, 1996. https://doi.org/10.1073/pnas.93.25.14559
  10. M. Deshmukh, J. Vasilakos, T. L. Deckwerth, P. A. Lampe, B. D. Shivers, and E. M. Johnson, Jr, "Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases", J. Cell Biol., Vol. 135, pp. 1341-1354, 1996. https://doi.org/10.1083/jcb.135.5.1341
  11. M. D. Johnson, H. Xiang, S. London, Y. Kinoshita, M. Knudson, M. Mayberg, S. J. Korsmeyer, and R. S. Morrison, "Evidence for involvement of Bax and p53, but not caspases, in radiation-induced cell death of cultured postnatal hippocampal neurons", J. Neurosci. Res., Vol. 54, pp. 721-733, 1998. https://doi.org/10.1002/(SICI)1097-4547(19981215)54:6<721::AID-JNR1>3.0.CO;2-1
  12. L. Stefanis, D. S. Park, W. J. Friedman, and L. A. Greene, "Caspase-dependent and -independent death of camptothecin-treated embryonic cortical neurons", J. Neurosci., Vol. 19, pp. 6235-6247, 1999.
  13. L. A. Selznick, T. S. Zheng, R. A. Flavell, and P. Rakie, "Amyloid beta-induced neuronal death is bax-dependent but caspase independent", J. Neuropathol. Exp. Neurol., Vol. 59, pp. 271-279, 2000. https://doi.org/10.1093/jnen/59.4.271
  14. M. Shanawaz, A. Thapa, and I. S. Park, "Stable activity of a deubiquitylating enzyme (Usp2-cc) in the presence of high concentrations of urea and its application to purify aggregation-prone peptides", Biochem. Biophys. Res. Commun., Vol. 359, pp. 801-805, 2007. https://doi.org/10.1016/j.bbrc.2007.05.186
  15. J. A. Watt, C. J. Pike, A. J. Walencewicz-Wasserman, and C. W. Cotman, "Ultrastructural analysis of $\beta$-amyloid induced apoptosis in cultured hippocampal neurons", Brain Res., Vol. 661, pp. 147-156, 1994. https://doi.org/10.1016/0006-8993(94)91191-6
  16. Y. Shi, "Mechanisms of caspase activation and inhibition during apoptosis", Mol. Cell, Vol. 9, pp. 459-470, 2002. https://doi.org/10.1016/S1097-2765(02)00482-3
  17. J. Harada and M. Sugimoto, "Activation of caspase-3 in $\beta$-amyloid induced apoptosis of cultured rat cortical neurons", Brain Res., Vol. 842, pp. 311-323, 1999. https://doi.org/10.1016/S0006-8993(99)01808-9
  18. C. M. Troy, S. A. Rabacchi, W. J. Friedman, T. F. Frappier, K. Brown, and M.L. Shelanski, "Caspase-2 mediates neuronal cell death induced by $\beta$-amyloid", J. Neurosci., Vol. 20, pp. 1386-1392, 2000.
  19. J. Saez-Valero, N. Angeretti, and G. Forloni, "Caspase-3 activation by beta-amyloid and prion protein peptides is independent from their neurotoxic effect", Neurosci. Lett., Vol. 293, pp. 207-210, 2000. https://doi.org/10.1016/S0304-3940(00)01532-9
  20. I. Budihardjo, H. Oliver, M. Lutter, X. Luo, and X. Wang, "Biochemical pathways of caspase activation during apoptosis. Annual Review of Cell and Developmental", Biology, Vol. 15, pp. 269-290, 1999.
  21. P. Picone, R. Carrotta, G. Montana, M. R. Nobile, P. L. S. Biagio, and M. Di Carlo, "$A{\beta}$ oligomers and fibrillar aggregates induce different apoptotic pathways in LAN5 neuroblastoma cell cultures", Biophys. J., Vol. 96, pp. 4200-4211, 2008.