Effect of Mycelial Extract of Clavicorona pyxidata on the Production of Amyloid $\beta$-Peptide and the Inhibition of Endogenous $\beta$-Secretase Activity in vitro

  • Lee, Tae-Hee (Department of Life Science, College of Natural Science, Dongguk University) ;
  • Park, Young-Il (Department of Biology, Graduate School, Dongguk University) ;
  • Han, Yeong-Hwan (Department of Life Science, College of Natural Science, Dongguk University)
  • 발행 : 2006.12.31

초록

Amyloid $\beta$-peptide (A$\beta$), which is a product of the proteolytic effect of $\beta$-secretase (BACE) on an amyloid precursor protein, is closely associated with Alzheimer's disease (AD) pathogenesis. There is sufficient evidence to suggest that a BACE inhibitor may reduce A$\beta$ levels, thus decreasing the risk of AD. In a previous study, an extract of Clavicorona pyxidata DGUM 29005 mycelia was found to inhibit the production of a soluble $\beta$-amyloid precursor protein (s$\beta$APP), A$\beta$, and BACE in neuronal cell lines. We sought to determine whether this mycelial extract exerts the same effect in human rhabdomyosarcoma A-204 and rat pheochromocytoma PC-12 cells. We found that the production of A$\beta$ decreased in a dose-dependent manner in the presence of the mycelial extract and that the concentration of A$\beta$ never exceeded $50{\mu}g/ml$. The presence of sAPP was detected in every culture medium to which the mycelial extract had been added and its concentration remained the same, regardless of the concentration of the extract used. Endogenous $\beta$-secretase activity in A-204 and PC-12 cellular homogenates also decreased in the presence of this extract. These cells, in culture, were not susceptible to the cytotoxic activity of the mycelial extract.

키워드

참고문헌

  1. Acquati, F., M. Accarino, C. Nucci, P. Fumagalli, L. Jovine, S. Ottolenghi, and R. Taramelli. 2000. The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region. FEBS Lett. 468, 59-64 https://doi.org/10.1016/S0014-5793(00)01192-3
  2. Bennett, B.D., S. Babu-Khan, R. Loeloff, J.C. Louis, E. Curran, M. Citron, and R. Vassar. 2000. Expression analysis of BACE2 in brain and peripheral tissues. J. Biol. Chem. 275, 20647-20651 https://doi.org/10.1074/jbc.M002688200
  3. Cai, H., Y. Wang, D. McCarthy, H. Wen, D.R. Borchelt, D.L. Price, and P.C. Wong. 2001. BACE1 is the major beta-secretase for generation of beta peptides by neurons. Nat. Neurosci. 4, 233-234 https://doi.org/10.1038/85064
  4. Capell, A., H. Steiner, M. Willem, H. Kaiser, C. Meyer, J. Walter, S. Lammich, G. Multhaup, and C. Haass. 2000. Maturation and pro-peptide cleavage of beta-secretase. J. Biol. Chem. 275, 30849-30854 https://doi.org/10.1074/jbc.M003202200
  5. Citron, M., T. Oltersdorf, C. Haass, L. McConlogue, A.Y. Hung, P. Seubert, C. Vigo-Palfrey, I. Lieberburg, and D.J. Selkoe. 1992. Mutation of the $\beta$-amyloid precursor protein in familial Alzheimer's disease increases $\beta$-protein production. Nature 360, 672-674 https://doi.org/10.1038/360672a0
  6. DeMattos, R.B., K.R. Bales, D.J. Cummins, J.C. Dodart, S.M. Paul, and D.M. Holtzman. 2001. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decrease brain A beta burden in a mouse model of Alzheimer's disease. Proc. Natl. Sci. USA. 98, 8850-8855
  7. Estus, S. 1997. Aggregated $\beta$-amyloid protein induces cortical neuronal apoptosis and concomitant 'apoptotic' pattern of gene induction. J. Neurosci. 17, 7736-7745 https://doi.org/10.1523/JNEUROSCI.17-20-07736.1997
  8. Felsenstein, K.M., L.W. Hunihan, and S.B. Roberts. 1994. Altered cleavage and secretion of a recombinant $\beta$-APP bearing the Swedish familial Alzheimer's disease mutation. Nat. Genet. 6, 251 https://doi.org/10.1038/ng0394-251
  9. Hass, C., C.A. Lemere, A. Capell, M. Citron, P. Seubert, D. Schenk, L. Lannfelt, and D.J. Selkoe. 1995. The Swedish mutation causes early-onset Alzheimer's disease by $\beta$-secretase cleavage within the secretase pathway. Nat. Med. 1, 1291-1296 https://doi.org/10.1038/nm1295-1291
  10. Haniu, M., P. Denis, Y. Young, E.A. Mendiaz, J. Fuller, J.O. Hui, B.D. Bennett, S. Kahn, S. Ross, T. Burgess, V. Katta, G. Rogers, R. Vassar, and M. Citron. 2000. Characterization of Alzheimer's beta-secretase protein BACE. A pepsin family member with unusual properties. J. Biol. Chem. 275, 21099-21106 https://doi.org/10.1074/jbc.M002095200
  11. Hiroshi, T. and T. Takeshi. 2001. Three novel alternatively spliced isoforms of the human beta-site amyloid precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-peptide production. Neurosci. Lett. 307, 9-12 https://doi.org/10.1016/S0304-3940(01)01912-7
  12. Huse, J.T., D.S. Pijak, G.J. Leslie, V.M. Lee, and R.W. Doms. 2000. Maturation and endosomal targeting of beta site amyloid precursor protein-cleaving enzyme. J. Biol. Chem. 275, 33729-33737 https://doi.org/10.1074/jbc.M004175200
  13. Hussain, I., D.J. Powell, D.R. Howlett, G.A. Chapman, L. Gilmour, P.R. Murdock, D.G. Tew, T.D. Meek, C. Chapman, K. Schneider, S.J. Ratcliffe, D. Tattersall, T.T. Testa, C. Southan, D.M. Ryan, D.L. Simmons, F.S. Walsh, C. Dingwall, and G. Christie. 2000. ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site. Mol. Cell Neurosci. 16, 609-619 https://doi.org/10.1006/mcne.2000.0884
  14. Koldamova, R.P., I.M. Lefterov, M. Staufenbiel, D. Wolfe, S. Huang, J.C. Glorioso, M. Walter, M.G. Roth, and J.S. Lazo. 2005. The liver X receptor ligand T0901217 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J. Biol. Chem. 280, 4079-4088 https://doi.org/10.1074/jbc.M411420200
  15. Lee, H.J., G.Y. Heo, K.B. Lee, I.K. Rhee, and K.S. Song. 1999. Inhibitory activities of basidiomycetes on prolyl endopeptidase, acetylcholinesterase, and coagulation. J. Kor. Soc. Agric. Chem. Biotechnol. 42, 336-343
  16. Lee, T.H., J.M. Kim, and Y.H. Han. 2006a. Optimized cultured condition and enzyme activity of the mycelia of Clavicorona pyxidata. Kor. J. Microbiol. 42, 98-102
  17. Lee, T.H., Y.I. Park, and Y.H. Han. 2006b. Effect of mycelial extract of Clavicorona pyxidata on acetylcholinesterase and $\beta$-secretase activity in vitro. J. Microbiol. 44, 502-507
  18. Luo, Y., B. Bolon, S. Kahn, B.D. Bennett, S. Babu-Khan, P. Denis, W. Fan, H. Kha, J. Zhang, and Y. Gong. 2001. Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat. Neurosci. 4, 231-232 https://doi.org/10.1038/85059
  19. Potempska, A., K. Mack, P. Mehta, K.S. Kim, and D.L. Miller. 1999. Quantification of sub-femtomole amounts of Alzheimer's amyloid $\beta$ peptides. J. Exp. Clin. 6, 14-21
  20. Selkoe, D.J. 1989. Biochemistry of altered brain proteins in Alzheimer's disease. Annu. Rev. Neurosci. 12, 463-469 https://doi.org/10.1146/annurev.ne.12.030189.002335
  21. Selkoe, D.J. 1991. The molecular pathology of Alzheimer's disease. Neuron 6, 487-498 https://doi.org/10.1016/0896-6273(91)90052-2
  22. Sinha, S., J.P. Anderson, R. Barbour, G.S. Basi, R. Caccavello, D. Davis, M. Doan, H.F. Dovey, N. Frigon, and J. Hong. 1999. Purification and cloning of amyloid precursor protein beta-secretase form human brain. Nature 402, 537-540 https://doi.org/10.1038/990114
  23. Vassar, R. 1999. $\beta$-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741 https://doi.org/10.1126/science.286.5440.735
  24. Walsh, D.M., M. Townsend, M.B. Podlisny, G.M. Shanker, J.V. Fadeeva, O.E. Agnaf, D.M. Hartley, and D.J. Selkoe. 2005. Certain inhibitors of synthetic amyloid $\beta$-peptide ($A{\beta}$) fibrillogensis block oligomerization of natural $A{\beta}$) and thereby rescue long-term potentiation. J. Neurosci. 25, 2455-2462 https://doi.org/10.1523/JNEUROSCI.4391-04.2005
  25. Yan, R., M.J. Bienkowski, M.E. Shuck, H. Miao, M.C. Troy, A.M. Pauley, J.R. Brashier, N.C. Stratman, W.R. Mathews, and A.E. Buhl. 1999. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature 402, 533-537 https://doi.org/10.1038/990107