Archives of Pharmacal Research

  • 제28권9호
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  • Pages.1073-1078
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  • 2005
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Mutant Presenilin 2 Increases Acetylcholinesterase Activity in Neuronal Cells

  • Nguyen Hong Nga (College of Pharmacy, Chungbuk National University) ;
  • Hwang Dae Youn (National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Kim Young Kyu (National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Yoon Do Young (Lab of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim Jae Hwa (Lab of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee Moon Soon (National Institute of Environmental Research) ;
  • Lee Myung Koo (College of Pharmacy, Chungbuk National University) ;
  • Yun Yeo Pyo (College of Pharmacy, Chungbuk National University) ;
  • Oh Ki Wan (College of Pharmacy, Chungbuk National University) ;
  • Hong Jin Tae (College of Pharmacy, Chungbuk National University)
  • 발행 : 2005.09.01
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초록

A presenilin 2 mutation is believed to be involved in the development of Alzheimer's disease. In addition, transgenic mice with a presenilin 2 mutation have been reported to have learning and memory impairments. In this study, exposing PC12 cells expressing mutant presenilin 2 to $50{\mu}M\;A{\beta}_{25-35},\;30mM$ L-glutamate and $50{\mu}M\;H_2O_2$ caused a significant increase in acetylcholine esterase activity. An in vivo study revealed high levels of this enzyme activity in the mutant presenilin 2 transgenic brains compared with the wild type presenilin 2 transgenic and non-transgenic samples. These results suggest that a mutant presenilin 2-induced neurodegeneration in Alzheimer's disease might be involved in the increase in acetylcholinesterase activity. These findings might help in the development of an appropriate therapeutic intervention targeting mutant presenilin 2-induced Alzheimer's disease.

키워드

참고문헌

  1. Alvarez, A., Alarcon, R., Opazo, C., Campos, E. O., Munoz, F.J., Calderon, F.H., Dajas, F., Gentry, M. K., Doctor, B. P., De Mello, F. G., and Inestrosa, N. C., Stable complexes involving acetylcholinesterase and amyloid beta peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils. J. Neurosci., 18, 3213-3223(1999)
  2. Alves da Costa, C., Paitel, E., Mattson, M. P., Amson, R., Telerman, A., Ancolio, K., and Checler, F., Wild-type and mutated presenilins 2 trigger p53-dependent apoptosis and down-regulate presenilin 1 expression in HEK293 human cells and in murine neurons. Proc. Natl. Acad. Sci. U.S.A., 99, 4043-4048 (2002) https://doi.org/10.1073/pnas.062059899
  3. Araki, W., Yuasa, K., Takeda, S., Takeda, K., Shirotani, K., Takahashi, K., and Tabira, T., Pro apoptotic effect of presenilin 2 (PS2) overexpression is associated with down regulation of Bcl2 in cultured neurons. J. Neurochem., 79,1161-1168 (2001) https://doi.org/10.1046/j.1471-4159.2001.00638.x
  4. Deng, G., Pike, C. J., and Cotman, C. W., Alzheimer's associated presenilin2 confers increased sensitivity to apoptosis in PC12 cells. FEBS Lett., 397, 50-54 (1996) https://doi.org/10.1016/S0014-5793(96)01142-8
  5. Ellman, G. L., Courtney, K. D., Andres, V. Jr., and Featherstone, R. M., A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 7, 88-95 (1961) https://doi.org/10.1016/0006-2952(61)90145-9
  6. Fodero, L. R., Mok, S. S., Losic, D., Martin, L. L., Aguilar, M. I., Barrow, C. J., Livett, B. G., and Small, D. H., Alpha7-nicotinic acetylcholine receptors mediate an Abeta (1-42)-induced increase in the level of acetylcholinesterase in primary cortical neurones. J. Neurochem., 88, 1186-1193 (2004) https://doi.org/10.1046/j.1471-4159.2003.02296.x
  7. Hu, W., Gray, N. W., and Brimijoin, S., Amyloid-beta increases acetylcholinesterase expression in neuroblastoma cells by reducing enzyme degradation. J. Neurochem., 86, 470-478 (2003) https://doi.org/10.1046/j.1471-4159.2003.01855.x
  8. Hwang, D. Y, Chae, K. R., Kang, T. S., Hwang, J. H., Lim, C. H., Kang, H. K., Goo, J. S., Lee, M. R., Lim, H. J., Min, S. H., Cho, J. Y, Hong, J. T., Song, C. W, Paik, S. G, Cho, J. S., and Kim, Y. K., Alterations in behavior, amyloid beta-42, caspase-3, and Cox-2 in mutant PS2 transgenic mouse model of Alzheimer's disease. FASEB J, 16, 805-813 (2002) https://doi.org/10.1096/fj.01-0732com
  9. Inestrosa, N. C., Alvarez, A, Perez, C. A., Moreno, R. D., Vicente, M., Linker, C., Casaneuva, O. I., Soto, C., and Garrido, J., Acetylcholinesterase accelerates assembly of amyloid beta peptides into Alzheimer's fibrils: Possible role of the periferal site of the enzyme. Neuron, 16, 881-891 (1996) https://doi.org/10.1016/S0896-6273(00)80108-7
  10. Janicki, S. M. and Monterio, M. J., Presenilin overexpression arrests cells in the G1 phase of cell cycle. Arrest potentiated by the Alzheimer's disease PS2 (N141I) mutant. Am. J. Pathol.,155, 135-144 (1999) https://doi.org/10.1016/S0002-9440(10)65108-5
  11. Janicki, S. and Montaeiro, M. J., Increase apoptosis arising from increased expression of the Alzheimer's diseaseassociated presenilin 2 mutation (N141I). J. Cell Biol., 139, 485-495 (1997) https://doi.org/10.1083/jcb.139.2.485
  12. Kuhl, D. E., Koeppe, R. A., Minoshima, S., Snyder, S. E., Ficaro, E. P., Foster, N. L., Frey, K. A., and Kilbourn, M. R., In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology, 52, 691-699 (1999) https://doi.org/10.1212/WNL.52.4.691
  13. Lee, S. Y., Hwang D. Y., Kim, Y. K., Lee, J. W., Shin, I. C., Oh, K. W., Lee, M. K., Lim, J. S., Yoon, D. Y., Hwang, S. J., and Hong, J. T., PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release. FASEB J., in press (2005)
  14. Lei, Y., Heng, Y. H., and Xue, J. Z., Increase expression of intranuclear AChE involved in apoptosls of SK-N-SH cells. Neurosci. Res., 42, 261-268 (2002) https://doi.org/10.1016/S0168-0102(02)00005-6
  15. Li, Y., Liu, L., Kang, J., Sheng, J. G., Barger, S. W., Mrak, R. E., and Griffin, W. S., Neuronal-glial interactions mediated by interleukin-1 enhance neuronal acetylcholinesterase activity and mRNA expression. J. Neurosci., 20, 149-155 (2000)
  16. Melo, J. B., Agostinho, P., and Oliveira, C. R., Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide. Neurosci. Res., 45, 117-127 (2003) https://doi.org/10.1016/S0168-0102(02)00201-8
  17. Mori, M., Nakagami, H., Morishita, R., Mitsuda, N., Yamamoto, K., Yoshimura, S., Ohkubo, N., Sato, N., Ogihara, T, and Kaneda, Y, N141l mutant presenilin 2 gene enhances neuronal cell' death and decrease bcl2 expression. Life Sci., 70, 2567-2580 (2002) https://doi.org/10.1016/S0024-3205(02)01514-X
  18. Nguyen, H. N., Lee, S. Y., Hwang, D. Y., Kim, Y. K., Yuk, D. Y., Lee, J. S., and Hong, J. T., Decrease in NF-kappaB, AP-1 and SP-1 activities in neuronal cells expressing presenilin 2. Neuroreport, 16; 731-735 (2005) https://doi.org/10.1097/00001756-200505120-00015
  19. Rees, T, Hammond, P. I., Soreq, H., Younkin, S., and Brimijoin, S., Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex. Neurobiol. Aging, 24, 777-787 (2003) https://doi.org/10.1016/S0197-4580(02)00230-0
  20. Rocchi, A., Pellegrini, S., Siciliano, G, and Murri, L., Causative and susceptibility genes for Alzheimer's disease. A review. Brain Res. Bull., 61, 1-24 (2003) https://doi.org/10.1016/S0361-9230(03)00067-4
  21. Saez-Valero, J., Fodero, L. R., White, A. R., Barrow, C. J., Small, D. H., Acetylcholinesterase is increased in mouse neuronal and astrocyte cultures after treatment with betaamyloid peptides. Brain Res., 965, 283-286 (2003) https://doi.org/10.1016/S0006-8993(02)04159-8
  22. Sberna, G., Saez-Valero, J., Beyreuther, K., Masters, C. L., and Small, D. H., The amyloid beta-protein of Alzheimer's disease increases acetylcholinesterase expression by increasing intracellular calcium in embryonal carcinoma P19 cells. J. Neurochem., 69, 1177-1184 (1997) https://doi.org/10.1046/j.1471-4159.1997.69031177.x
  23. Shen, Z. X., Brain cholinesterase: The molecular and cellular basis of Alzheimer's disease. Med. Hypotheses, 63, 308-321 (2004) https://doi.org/10.1016/j.mehy.2004.02.031
  24. Song, Y. S., Park, H. J., Kim, S. Y., Lee, S. H., Yoo, H. S., Lee, H. S., Lee, M. K., Oh, K. W., Kang, S. K., Lee, S. E., and Hong, J. T., Protective role of Bcl-2 on beta-amyloid-induced cell death of differentiated PC12 cells: Reduction of NF-kappaB and p38 MAP kinase activation. Neurosci. Res., 49, 69-80 (2004) https://doi.org/10.1016/j.neures.2004.01.010
  25. Tamotsu, H. G, Atsushi, T, Yoshihisa, W., Naoyuki, I., Takashi, M., and Takeshi, T, A unifying model for functional difference and redundancy of presenilin-1 and -2 in cell apoptosis and differentiation. Gene, 34257, 1-9 (2003)
  26. Vito, P., Lacana, E., and D'Adamio, L., Interfering with apoptosis: Ca-binding protein ALG-2 and Alzheimer's disease gene ALG-3. Science, 271, 521-525 (1996) https://doi.org/10.1126/science.271.5248.521
  27. Vito, P., Wolozin, B., Ganjei, J. K., Iwasaki, K., Lacana, E., and D'Adamio, L., Requirement of the familial Alzheimer's disease gene PS2 for apoptosis. Opposing effect of ALG-3. J. Biol. Chem., 271, 31025-31028 (1996) https://doi.org/10.1074/jbc.271.49.31025
  28. Yang, L., He, H. Y., Zhang, X. J., Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells. Neurosci. Res., 42, 261-268 (2002) https://doi.org/10.1016/S0168-0102(02)00005-6
  29. Zhang, H. Y., Brimijoin, S., and Tang, X. C., Apoptosis induced by beta-amyloid 25-35 in acetylcholinesterase-overexpressing neuroblastoma cells. Acta Pharmacol. Sin., 24, 853-858 (2003)