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Effects Amyloid Beta Peptide on the Inflammatory Response in Neuronal Cells

베타아밀로이드가 신경세포에 미치는 염증 작용 연구

  • Received : 2013.08.06
  • Accepted : 2013.08.23
  • Published : 2013.08.30

Abstract

Amyloid ${\beta}$ peptide (A${\beta}$) still best known as a molecule to cause Alzheimer's disease (AD). AD is characterized by the accumulation and deposition of A${\beta}$ within the brain, leading to neuronal cell loss and perturbation of synaptic function by causing free radical formation, inflammation and apoptosis. We investigated the inflammatory action of A${\beta}$ on two types of brain cells, neuronal cells (SH-SY5Y) and neuroglia cells (C6), and its mechanism. We measured the production of NO-iNOS, TNF-${\alpha}$, and ICAM-1 using RT-PCR and Western blot analysis less than the concentration of cytotoxic effects (> 70% survivability). A${\beta}$ had no effect on the production of NO and TNF-${\alpha}$, but significantly increases of iNOS and ICAM-1. Based on this, we suggest that the inflammatory effect of A${\beta}$ results from the action of ICAM-1 in neuronal cells, rather than the release of inflammatory mediators such as NO and TNF-${\alpha}$ in neuroglia cells. In addition, we confirmed whether p53 was related to the action of A${\beta}$ by using SH-SY5Y ($p53^{-/-}$) dominant cells. Neither the expression of p53 nor the cytotoxicity of SH-SY5Y ($p53^{-/-}$) cells were directly affected by A${\beta}$. However, ICAM-1 was not expressed in SH-SY5Y ($p53^{-/-}$) cells. This means that p53- independent pathway exists in the expression of ICAM-1 by A${\beta}$ while p53 plays a role as an on-and-off switch.

Keywords

References

  1. Pietrzik, C. and C. Behl (2005) Concepts for the treatment of Alzheimer's disease: Molecular mechanisms and clinical application. Int. J. Exp. Pathol. 86: 173-185. https://doi.org/10.1111/j.0959-9673.2005.00435.x
  2. Silverberg, G. D., M. Mayo, T. Saul, J. Carvalho, and D. McGuire (2004) Novel ventriculo-peritoneal shunt in Alzheimer's disease cerebrospinal fluid biomarkers. Expert Rev. Neurother. 4: 97-107. https://doi.org/10.1586/14737175.4.1.97
  3. Barril, X., M. Orozco, and F. J. Luque (2001) Towards improved acetylcholinesterase inhibitors: A structural and computational approach. Mini Rev. Med. Chem. 1: 255-266. https://doi.org/10.2174/1389557013406828
  4. Gong, Y., L. Chang, K. L. Viola, P. N. Lacor, M. P. Lambert, C. E. Finch, G. A. Krafft, and W. L. Klein (2003) Alzheimer's disease-affected brain: Presence of oligomeric A-beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc. Natl. Acad. Sci. USA. 100: 10417-10422. https://doi.org/10.1073/pnas.1834302100
  5. Yankner, B. A., L. K. Duffy, and D. A. Kirschner (1990) Neurotrophic and neurotoxic effects of amyloid beta protein: Reversal by tachykinin neuropeptides. Science 250: 279-282. https://doi.org/10.1126/science.2218531
  6. Mattson, M. P., B. Cheng, D. Davis, K. Bryant, I. Lieberburg, and R. E. Rydel (1992) beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J. Neurosci. 12: 376-389.
  7. Pike, C. J., D. Burdick, A. J. Walencewicz, C. G. Glabe, and D. W. Cotman (1993) Neurodegeneration induced by beta-amyloid peptides in vitro: The role of peptide assembly state. J. Neurosci. 13: 1676-1687.
  8. Takashima, A., K. Noguchi, K. Sato, T. Hoshino, and K. Imahori (1993) Tau protein kinase I is essential for amyloid beta-proteininduced neurotoxicity. Proc. Natl. Acad. Sci. USA. 90: 7789-7793. https://doi.org/10.1073/pnas.90.16.7789
  9. Behl, C., J. B. Davis, R. Lesley, and D. Schubert (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77: 817-827. https://doi.org/10.1016/0092-8674(94)90131-7
  10. Shearman, M. S., C. I. Ragan, and L. L. Iversen (1994) Inhibition of PC12 cell redox activity is a specific, early indicator of the mechanism of beta-amyloid- mediated cell death. Proc. Natl. Acad. Sci. USA. 91: 1470-1474. https://doi.org/10.1073/pnas.91.4.1470
  11. Frautschy, S. A., A. Baird, and G. M. Cole (1991) Effects of injected Alzheimer beta-amyes in rat brain. Proc. Natl. Acad. Sci. USA. 88: 8362-8366. https://doi.org/10.1073/pnas.88.19.8362
  12. Kowall, N. W., M. F. Beal, J. Busciglio, L. K. Duffy, and B. A. Yankner (1991) An in vivo model for the neurodegenerative effects of beta-amyloid and protection by substance P. Proc. Natl. Acad. Sci. USA. 88: 7247-7251. https://doi.org/10.1073/pnas.88.16.7247
  13. Selkoe, D. J. (2001) Alzheimer's disease: Genes, proteins, and therapy. Physiol. Rev. 81: 741-766.
  14. Mattson, M. P. (2004) Pathways towards and away from Alzheimer's disease. Nature 430: 631-639. https://doi.org/10.1038/nature02621
  15. Reddy, P. H. and M. F. Beal (2005) Are mitochondria critical in the pathogenesis of Alzheimer's disease? Brain. Res. Brain. Res. Rev. 49: 618-632. https://doi.org/10.1016/j.brainresrev.2005.03.004
  16. Reddy, P. H. and S. Weeney (2006) Mapping cellular transcriptosomes in autopsied Alzheimer's disease subjects and relevant animal models. Neurobiol. Aging 27: 1060-1077. https://doi.org/10.1016/j.neurobiolaging.2005.04.014
  17. Tanzi, R. E. and L. Bertram (2005) Twenty years of the Alzheimer's disease amyloid hypothesis: A genetic perspective. Cell 120: 545-555. https://doi.org/10.1016/j.cell.2005.02.008
  18. Skaper, S. D. (2012) Alzheimer's disease and amyloid: Culprit or coincidence? Int. Rev. Neurobiol. 102: 277-316. https://doi.org/10.1016/B978-0-12-386986-9.00011-9
  19. Rubio-Perez, J. M. and J. M. Morillas-Ruiz (2012) A review: Inflammatory process in Alzheimer's disease, role of cytokines. Scientific World J. 2012: 756357.
  20. Selkoe, D. J. (2005) Defining molecular targets to prevent Alzheimer disease. Arch Neurol. 62: 192-195. https://doi.org/10.1001/archneur.62.2.192
  21. Selkoe, D. J. (2003) Folding proteins in fatal ways. Nature 426: 900-904. https://doi.org/10.1038/nature02264
  22. Rich, J. B., D. X. Rasmusson, M. F. Folstein, K. A. Carson, C. Kawas, and J. Brandt (1995) Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology 45: 51-55. https://doi.org/10.1212/WNL.45.1.51
  23. Wei, X., Y. Zhang, and J. Zhou (1999) Alzheimer's disease-related gene expression in the brain of senescence accelerated mouse. Neurosci. Lett. 268: 139-142. https://doi.org/10.1016/S0304-3940(99)00396-1
  24. Hu, J., K. T. Akama, G. A. Krafft, B. A. Chromy, and L. J. Van Eldik (1998) Amyloid-beta peptide activates cultured astrocytes: Morphological alterations, cytokine induction and nitric oxide release. Brain. Res. 785: 195-206. https://doi.org/10.1016/S0006-8993(97)01318-8
  25. Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival: Application of proliferation and cytotoxicity assays. J. Immunol. Methods. 65: 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  26. Ding, A. H., C. F. Nathan, and D. J. Stuehr (1988) Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. comparison of activating cytokines and evidence for independent production. J. Immunol. 141: 2407-2414.
  27. Barron, K. D. (1995) The microglial cell. A historical review. J. Neurol. Sci. 134: 57-68.
  28. Boje, K. M. and P. K. Arora (1992) Microglial-produced nitric oxide and reactive nitrogen oxide mediate neuronal cell death. Brain Res. 587: 250-256. https://doi.org/10.1016/0006-8993(92)91004-X
  29. Dawson, T. M., J. Zhang, V. L. Dawson, and S. H. Snyder (1994) Nitric oxide: Cellular regulation and neuronal injury. Prog. Brain Res. 103: 365-369. https://doi.org/10.1016/S0079-6123(08)61150-4
  30. Kleinert, H., P. M. Schwarz, and U. Frstermann (2003) Regulation of the expression of inducible nitric oxide synthase. Biol. Chem. 384: 1343-1364.
  31. Satoh, J., L. F. Kastrukoff, and S. U. Kim (1991) Cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human oligodendrocytesand astrocytes. J. Neuropathol. Exp. Neurol. 50: 215-216. https://doi.org/10.1097/00005072-199105000-00004
  32. Ballestas, M. E. and E. N. Benveniste. (1995) Interlukin 1-beta and tumor necrosis factor-alpha-mediated regulation of ICAM-1 gene expression in astrocytes requires protein kinase C activity. Glia 14: 267-278. https://doi.org/10.1002/glia.440140404
  33. Buizza, L., C. Prandelli, S. A. Bonini, A. Delbarba, G. Cenini, C. Lanni, E. Buoso, M. Racchi, S. Govoni, M. Memo, and D. Uberti (2013) Conformational altered p53 affects neuronal function: Relevance for the response to toxic insult and growth-associated protein 43 expression. Cell Death Dis. 4: e484. https://doi.org/10.1038/cddis.2013.13
  34. Gorgoulis, V. G., P. Zacharatos, A. Kotsinas, D. Kletsas, G. Mariatos, V. Zoumpourlis, K. M. Ryan, C. Kittas, and A. G. Papavassiliou (2003) p53 activates ICAM-1 (CD54) expression in an $NF{\kappa}B$-independent manner. EMBO J. 22:1567-1578. https://doi.org/10.1093/emboj/cdg157
  35. Gorgoulis, V. G., H. Pratsinis, P. Zacharatos, C. Demoliou, F. Sigala, P. J. Asimacopoulos, A. G. Papavassiliou, and D. Kletsas (2005) p53-dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions. Lab. Invest. 85:502-511. https://doi.org/10.1038/labinvest.3700241