Skip to main content
Log in

The Effect of Alpha-Tocopherol on the Activity of Acetylcholinesterases from Different Sources

  • Experimental Articles
  • Published:
Neurochemical Journal Aims and scope Submit manuscript

Abstract

We found a significant inhibitory effect of alpha-tocopherol (TPh) on soluble commercial preparations of acetylcholinesterase (AChE), that is, human recombinant AChE (hAChE) and AChE from the electric eel. The inhibition occurs via the interaction of the phytol chain with the peripheral anionic site of AChE. However, TPh fails to inhibit the molecular forms of the enzyme that are important for the development of Alzheimer’s disease, in particular, AChE in erythrocytes and cholinergic membrane-bound AChE in the mouse brain, while the latter is even activated with the administration of TPh in vivo. When selecting a model for screening the substances with anticholinesterase properties for the development of new anti-AD therapies, it should be noted that the inhibition of commercial preparations of enzymes may not necessarily be indicative of an anticholinesterase effect in the body.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

ACh:

acetylcholine

ATCh:

acetylthiocholine

AChE:

acetylcholinesterase

hAChE:

human recombinant AChE

AD:

Alzheimer’s disease

BTCh:

butyrylthiocholine

BChE:

butyrylcholinesterase

DTNB:

5;5’-dithiobis(2-nitrobenzoic acid)

OS:

oxidative stress

PAS:

peripheral anionic site

LPO:

lipid peroxidation

TPh:

alpha-tocopherol

GPI:

glycosylphosphatidylinositol

PRiMA:

proline-rich membrane anchor

References

  1. Kim, G.N., Kim, J.E., Rhie, S.J., and Yoon, S., Exp. Neurobiol, 2015, vol. 24, no. 4, pp. 325–340.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Aliev, G., Obrenovich, M.E., Reddy, V.P., Shenk, J.C., Moreira, P.I., Nunomura, A., Zhu, X., Smith, M.A., and Perry, G., Mini. Rev. Med. Chem, 2008, vol. 8, no. 13, pp. 1395–1406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bittner, D.M., Journal of Clinical Psychopharmacology, 2009, vol. 29, no. 5, pp. 511–512.

    Article  PubMed  Google Scholar 

  4. Grimm, M.O.W., Mett, J., and Hartmann, T., Int. J. Mol. Sci, 2016, vol. 17, no. 11.

    Google Scholar 

  5. Farina, L., Llewellyn, D., Isaac, M.G.E.K.N., and Taber N., Cochrane Database of Systematic Reviews, 2017, no. 4, CD002854.

    PubMed  Google Scholar 

  6. La Fata, G., Weber, P., and Mohajer, M.H., Nutrients, 2014, vol. 6, pp. 5453–5472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lloret, A., Badia, M.C., Mora, N.J., Pallardo, F.V., Alonso, M.D., and Vina, J., J. Alzheimer D., vol. 17, no. 1, pp. 143–149.

  8. Massolie, J., Neurosignals, 2002, pp. 130–143.

  9. Perrier, A.L., Massoulie, J., and Krejci, E., Neuron, 2002, vol. 33, pp. 275–285.

    Article  CAS  PubMed  Google Scholar 

  10. Campanary, M.-L., Navarette, F., Ginsberg, D., Manzanares, J., Saez-Valero, J., and Garcia-Ayllon, M.-S., J. Alzheimer’s D., 2016, vol. 53, pp. 831–841.

    Article  CAS  Google Scholar 

  11. Ferrari, G.V., Canales, M.A., Shin, I., Weiner, L.M., Silman, I., and Inestrosa, N.C., Biochemistry, 2001, vol. 40, pp. 10447–10457.

    Article  CAS  PubMed  Google Scholar 

  12. Inestrosa, N.C., Sagal, J.P., and Colombres, M., Sub-cell. Biochem., 2005, vol. 38, pp. 299–317.

    Article  CAS  Google Scholar 

  13. Inestrosa, N.C., Dinamarca, M.C., and Alvarez, A., FEBS J., 2008, vol. 275, no. 4, pp. 625–632.

    Article  CAS  PubMed  Google Scholar 

  14. Renn, B.N., Asghar-Ali, A.A., Thielke, S., Catic, A., Martini, S.R., Mitchell, B.G., and Kunik, M.E., Am. J. Geriatr. Psychiatry, 2018, vol. 26, no. 2, pp. 134–147.

    Article  PubMed  Google Scholar 

  15. Wang, Yu., Wang, H., and Chen, H.-Zh., Current Neuropharmacology, 2016, vol. 14, pp. 346–375.

    Google Scholar 

  16. Darvesh, S. and Reid, G.A., Chem. Biol. Ineract., 2016, vol. 259, pp. 307–312.

    Article  CAS  Google Scholar 

  17. Diamant, S., Podoly, E., Friedler, A., Ligumsky, H., Livnah, O., and Soreq, H., PNAS, vol. 3, no. 23, pp. 8628–8633.

  18. Stasiuk, M., Janiszewska, A., and Kozubek, A., Nutrients, 2014, vol. 6, pp. 1823–1831.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Takahashi, K., Takisawa S., Shimokado K., Kono N., Arai H., and Ishigami A., Eur. J. Nutr., 2017, vol. 56, pp. 1317–1327.

    Article  CAS  PubMed  Google Scholar 

  20. Vatassery, G.T., Lipids, 1978, vol. 13, no. 11, pp. 828–831.

    Article  CAS  PubMed  Google Scholar 

  21. Vatassery, G.T., Angerhofer, C.K., Knox, C.A., and Deshmukh, D.S., Biochim. Biophys. Acta, 1984, vol. 792, no. 2, pp. 118–122.

    Article  CAS  PubMed  Google Scholar 

  22. Shadnia, S., Dasgar, M., Taghikhani, S., Mohammadirad, A., Khorasani, R., and Abdollahi, M., Toxicol. Mech. Methods, 2007, vol. 17, no. 2, pp. 109–115.

    Article  CAS  PubMed  Google Scholar 

  23. Hajos, F., Brain Res., 1975, vol. 93, no. 3, pp. 485–489.

    Article  CAS  PubMed  Google Scholar 

  24. Lowry, O.H., Rosebrough, N.J., Fare, A.L., and Randall, R., J, J. Biol. Chem., 1951, vol. 193, no. 1, pp. 265–275.

    CAS  PubMed  Google Scholar 

  25. Ellman, G.L., Courtney, K.D., Andres, V., Jr., and Featherstone, R.M., Biochem. Pharmacol., 1961, no. 7, pp. 88–96.

    Article  CAS  Google Scholar 

  26. Worek, F., Mast, U., Kiderlen, D., Diepold, C., and Eyer, P., Clin. Chim. Acta, 1999, vol. 88, nos. 1–2, pp. 73–90.

    Article  Google Scholar 

  27. Steinberg, N., Roth, E., and Silman, I., Biochemistry International, 1990, vol. 21, no. 6, pp. 1043–1050.

    CAS  PubMed  Google Scholar 

  28. Chelliah, J., Smith, J.D., and Fariss, M.W., Biochim. Biophys. Acta, 1994, vol. 1206, pp. 17–26.

    Article  CAS  PubMed  Google Scholar 

  29. Johnson, G. and Moore, S.W., Current Pharmaceutical Design, 2006, vol. 12, pp. 217–225.

    Article  CAS  PubMed  Google Scholar 

  30. Kosenko, E.A., Aliev, G., Tikhonova, L.A., Li, Y., Poghosyan, A.C., and Kaminsky, Y.G., CNS Neurol. Disord. Drug Targets, 2012, vol. 7, pp. 926–932.

    Article  Google Scholar 

  31. Carelli-Alinovi, C. and Misiti, F., Frontiers in Aging Neuroscience, 2017, vol. 9.

  32. Gilca, M., Lixandru, D., Gaman, L., Virgolici, B., Atanasiu, V., and Stoian, I., Alzheimer. Dis. Assoc. Disord., 2014, vol. 28, pp. 358–363.

    Article  CAS  PubMed  Google Scholar 

  33. Fatkullina, L.D., Molochkina, E.M., Zorina, O.M., Podchufarova, D.E., Gavrilova, S.I., Fedorova, Ya. B., Klyushnik, T.P., and Burlakova, E.B., Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova, 2013, vol. 113, no. 6, pp. 62–67.

    CAS  Google Scholar 

  34. Lan, J., Liu, J., Zhao, P., Xue, R., Zhang, N., Zhang, P., Zhao, P., Zheng, F., and Sun, X., Age and Ageing, 2015, vol. 44, no. 3, pp. 458–464.

    Article  PubMed  Google Scholar 

  35. Pratico, D., Biofactors, 2012, vol. 38, no. 2, pp. 90–97.

    Article  CAS  PubMed  Google Scholar 

  36. Belov, V.V., Maltseva, E.L., and Palmina, N.P., in Chemical Reactions in Gas, Solid and Liquid Phases. Synthesis, Properties and Application., Zaikov, G.E., Ed., N.Y.: Nova Publisher Inc., 2001, pp. 29–43.

  37. Azzi, A., Free Radic. Biol. Med., 2007, vol. 43, pp. 16–21.

    Article  CAS  PubMed  Google Scholar 

  38. Brigelius-Flohe, R., Free Rad. Biol. Med., 2009, vol. 46, pp. 545–554.

    Article  CAS  Google Scholar 

  39. Azzi, A., Gysin, L., Kempna, P., Munteanu, A., Villacorta, L., Visarius, T., and Zingg, J.H., Biol. Chem., 2004, vol. 385, no. 7, pp. 585–591.

    Article  CAS  PubMed  Google Scholar 

  40. Hicks, D., John, D., Makova, N.Z., Henderson, Z., Nalivaeva, N.N., and Turner, A.J., J. Neurochem., 2011, vol. 116, no. 5, pp. 742–746.

    Article  CAS  PubMed  Google Scholar 

  41. Atkinson, J., Epand, R.-F., and Epand, R.-M., Free Radic. Biol. Med., 2008, vol. 44, pp. 739–764.

    Article  CAS  PubMed  Google Scholar 

  42. Xie, H.Q., Leung, K.W., Chen, V.P., Chan, G.K., Xu, S.L., Guo, A.J., Zhu, K.Y., Zheng, K.Y., Bi, C.W., Zhan, J.Y., Chan, W.K., Choi, R.C., and Tsim K.W., Chem. Biol. Interact, 2010, vol. 187, nos. 1–3, pp. 78–83.

    Article  CAS  PubMed  Google Scholar 

  43. Atkinson, J., Harroun, Th., Wassall, R., Stillwell, W., and Katsaras, J., Mol. Nutr. Food Res., 2010, vol. 54, pp. 641–651.

    Article  CAS  PubMed  Google Scholar 

  44. Stocker, A. and Azzi, A., Antioxidants and Redox Signaling, 2000, vol. 2, no. 3, pp. 397–404.

    Article  CAS  PubMed  Google Scholar 

  45. Nava, Ph., Ceccini, M., Chirico, S., Gordon, H., Morley, S., Manor, D., and Atkinson, J., Bioorganic and Medicinal Chemistry, 2006, vol. 14, pp. 3721–3736.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. M. Molochkina.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Molochkina, E.M., Treshchenkova, Y.A. The Effect of Alpha-Tocopherol on the Activity of Acetylcholinesterases from Different Sources. Neurochem. J. 13, 36–42 (2019). https://doi.org/10.1134/S1819712419010161

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1819712419010161

Keywords

Navigation