Skip to main content
SpringerLink
Log in

PC12 cells transfected with human mutant gene causing one of Alzheimer’s disease forms have a high sensitivity to oxidative stress

  • Comparative and Ontogenic Biochemistry
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

Used in this work are PC12 cells transfected with human gene expressing amyloid-precursor protein of β-peptide and carrying the so-called “Swedish mutation” leading to the appearance of one of Alzheimer’s disease family forms. It has been shown that the PC12 cells transfected with this mutant gene, at action of various hydrogen peroxide concentrations, die to the significant greater degree than the used for comparison PC12 cells transfected with analogous human gene of the wild type or than vector-transfected cells. It has been found that ganglioside GM1 at micro-or nanomolar concentrations is able to increase viability of the PC12 cells transfected with the mutant gene causing a significant accumulation of endogenous amyloid β-peptide. The obtained data confirm an important role of oxidative stress in injury and death of brain nerve cells in Alzheimer’s disease.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Martin, B.L., Schrader-Fisher, G., Husciglin, J., Duke, M., Paganetti, P., and Yankner, B.A., Intracellular Accumulation of β-Amyloid in Cells Expressing the Swedish Mutant Amyloid Precursor Protein. J. Biol. Chem., 1995, vol. 270, pp. 26 727–26 730.

    CAS  Google Scholar 

  2. Perez, R.G., Squazzo, S.L., and Koo, E.H., Enhanced Release of Amyloid β-Protein from Codon 670/671 “Swedish” Mutant β-Amyloid Precursor Protein Occurs in Both Secretary and Endocytic Pathways. J. Biol. Chem., 1995, vol. 271, pp. 9100–9107.

    Google Scholar 

  3. Brouwers, S., Sleegers, K., Engelborghs, S., Bogaerts, Y., Serneels, S., Kamali, K., Corsmit, E., de Leemheir, E., Martin, J.J., de Dein, P.P., Broeckhoven, C., and van’ Theuns, J., Genetic Risk and Transcriptional Variability of Amyloid Precursor Protein in Alzheimer’s Disease, Brain, 2006, vol. 129, pp. 2984–2991.

    Article  PubMed  Google Scholar 

  4. Vetrivel, K.S., Zhang, Y.W., Xu, H., and Thinakaran, G., Pathological and Physiological Functions of Presenilins, Molec. Neurodegener., 2006, vol. 1, p. 4.

    Article  Google Scholar 

  5. Carter, D.B., Dunn, E., McKinley, D.D., Stratman, N.C., Boyle, T.P., Kulper, S.L., Oostveen, J.A., Weaver, R.J., Bolter, J.A., and Gurney, M.E., Human Apolipoprotein E4 Accelerates Beta-Amyloid Deposition in APP SW Transgenic Mouse Brain, Ann. Neurol., 2001, vol. 50, pp. 468–475.

    Article  CAS  PubMed  Google Scholar 

  6. Gau, J.T., Steinhilb, M.L., Kao, T.C., D’Amato, C.J., Gaut, J.R., Frey, K.A., and Turner, R.S., Stable Beta-Secretase Activity and Presynaptic Cholinergic Markers during Progressive Central Nervous System Amyloidogenesis in Tg2576 Mice, Am. J. Pathol., 2002, vol. 160, pp. 731–738.

    CAS  PubMed  Google Scholar 

  7. Marques, C., Keil, U., Bonert, A., Steiner, B., Haass, C., Muller, W.E., and Eckert, A., Neurotoxic Mechanisms Caused by Alzheimer’s Disease-Linked Swedish Amyloid Precursor Protein Mutation, J. Biol. Chem., 2003, vol. 278, pp. 28 294–28 302.

    CAS  Google Scholar 

  8. Matsuoki, Y., Saito, M., LaFrancois, J., Saito, M., Gaynor, K., Olm, V., Wang, L., Casey, E., Lu, Y., Shiratori, C., Lemere, C., and Duff, K., Novel Therapeutic Approach for the Treatment of Alzheimer’s Disease by Peripheral Administration of Agents with Affinity to Beta Amyloid, J. Neurosci., 2003, vol. 23, pp. 29–33.

    Google Scholar 

  9. Eckert, A., Steiner, B., Marques, C., Leutz, S., Roming, H., Haass, C., and Muller, W.E., Elevated Vulnerability to Oxidative Stress-Induced Cell Death and Activation of Caspase-3 by the Swedish Amyloid Precursor Protein Mutation, J. Neurochem. Res., 2001, vol. 64, pp. 183–192.

    CAS  Google Scholar 

  10. Fighera, M.R., Bonini, J.S., de Oliveira, T.G., Frussa-Filho, R., Rocha, J.B., Dutra-Filho, C.S., Rubin, M.A., and Mello, C.F., GM 1 Ganglioside Attenuates Convulsions and Thiobarbituric Acid Reactive Substances Production Induced by Intrastriatal Injection of Methylmalonic Acid, Int. J. Biochem. Cell Biol., 2003, vol. 35, pp. 465–473.

    Article  CAS  PubMed  Google Scholar 

  11. Choi, J.S., Kim, J.A., and Joo, C.K., Activation of MAPK and CREB by GM1 Induces Survival of RGCs in the Retina with Axotomized Nerve, Invest. Ophthalmol. Vis. Sci., 2003, vol. 44, pp. 1747–1752.

    Article  PubMed  Google Scholar 

  12. Bachis, A. and Mocchetti, I., Semisynthetic Sphingoglycolipid LIGA20 Is Neuroprotective Against Human Immunodeficiency Virus-gp120-Mediated Apoptosis, J. Neurosci. Res., 2006, vol. 83, pp. 890–896.

    Article  CAS  PubMed  Google Scholar 

  13. Hadjiconstantinou, M. and Neff, N.H., GM1 Ganglioside: in vivo and in vitro Trophic Actions on Central Neurotransmitter Systems, J. Neurochem., 1998, vol. 70, pp. 1335–1345.

    Article  CAS  PubMed  Google Scholar 

  14. Avrova, N.F., Victorov, I.V., Tyurin, V.A., Zakharova, I.O., Sokolova, T.V., Andreeva, N.A., Stelmaschuk, E.V., Tyurina, Y.Y., and Gonchar, V.S., Inhibition of Glutamate-Induced Intensification of Free Radical Reactions by Gangliosides: Possible Role in Their Protective Effect in Rat Cerebellar Granule Cells and Brain Synaptosomes, Neurochem. Res., 1998, vol. 23, pp. 945–952.

    Article  CAS  PubMed  Google Scholar 

  15. Mahadik, S.P., Bharucha, V.A., Stadlin, A., Ortiz, A., and Karpiak, S.E., Loss and Recovery of Activities of α+ and α Isozymes of Na+, K+-AT-Pase in Cortical Focal Ischemia: GM1 Ganglioside Protects Plasma Membrane Structure and Functions, J. Neurosci. Res., 1992, vol. 32, pp. 209–220.

    Article  CAS  PubMed  Google Scholar 

  16. Sautter, J., Hoglinger, G.U., Oertel, W.H., and Earl, C.D., Systemic Treatment with GM1 Ganglioside Improve Survival and Function of Cryopreserved Embryonic Midbrain Grafted to the 6-Hydroxydopamine-Lesioned Striatum, Exp. Neurol., 2000, vol. 164, pp. 121–129.

    Article  CAS  PubMed  Google Scholar 

  17. Augustinsson, L.E., Blennow, K., Blomstrand, C., and Brane, G., Intracerebroventricular Administration of GM1 Ganglioside in Presenile Alzheimer’s Disease, Dement. Geriatr. Gogn. Disord., 1997, vol. 8, pp. 26–33.

    Article  CAS  Google Scholar 

  18. Schneider, J.S., Roeltgen, D.P., Mancall, E.L. Chapas-Crilly, J., Rothblat, D.S., and Tatarian, G.T., Parkinson’s Disease: Improved Function with GM1 Ganglioside Treatment in a Randomized Placebo-Controlled Study, Neurology, 1998, vol. 50, pp. 1630–1636.

    CAS  PubMed  Google Scholar 

  19. Svennerholm, L., Brane, G., Karlsson, I., Lekman, A., Ramstrom, I., and Wikkelso, C., Alzheimer’s Disease-Effect of Continuous Intracerebroventricular Treatment with GM1 Ganglioside and a Systematic Activation Programme, Dement. Geriatr. Cogn. Disord., 2002, vol. 14, pp. 128–136.

    Article  CAS  PubMed  Google Scholar 

  20. Pope-Coleman, A. and Schneider, J.S., Effect of Chronic GM1 Ganglioside Treatment on Cognitive and Motor Deficits in a Slowly Progressing Model of Parkinsonism in Non-Human Primates, Restor. Neurol. Neirosci., 1998, vol. 12, pp. 255–266.

    CAS  Google Scholar 

  21. Vassault, A., Lactate Dehydrogenase: UV-Method with Pyruvate and NADH, Methods of Enzymatic Analysis, Bergmeyer, H.U., Ed., Weinheim: Verlag Chemie, 1983, vol. 3, pp. 118–126.

    Google Scholar 

  22. Folch, J., Lees, M., and Sloan-Stanley, G.H., A Simple Method for Isolation and Purification of Total Lipids from Animal Tissue, J. Biol. Chem., 1957, vol. 226, pp. 497–509.

    CAS  PubMed  Google Scholar 

  23. Tyurin, V.A., Tyurina, Yu.Yu., and Avrova, N.F., Ganglioside-Dependent Factor, Inhibiting Lipid Peroxidation in Rat Brain Synaptosomes, Neurochem. Int., 1992, vol. 20, pp. 401–407.

    Article  CAS  PubMed  Google Scholar 

  24. Eckert, A., Marques, C., Keil, U., Schussel, K., and Muller, W.E., Increased Apoptotic Cell Death in Sporadic and Genetic Alzheimer’s Disease, Ann. N. Y. Acad. Sci., 2003, vol. 1010, pp. 604–609.

    Article  CAS  PubMed  Google Scholar 

  25. Sokolova, T.V., Furaev, V.V., Yurlova, L.A., and Avrova, N.F., Effect of GM1 Ganglioside on Intracellular Concentration of Free Calcium and Viability of PC12 Cells at Induction of Oxidative Stress, Neurokhimiya, 2005, vol. 22, no. 4, pp. 266–272.

    CAS  Google Scholar 

  26. Avrova, N.F., Zakharova, I.O., Tyurin, V.A., Tyurina, Y.Y., Gamaley, I.A., and Schepetkin, I.A., Different Metabolic Effects of Ganglioside GM1 in Brain Synaptosomes and Phagocytic Cells, Neurochem. Res., 2002, vol. 27, pp. 751–759.

    Article  CAS  PubMed  Google Scholar 

  27. Fighera, M.R., Bonini, J.S., Frussa-Filho, R., Dutra-Filho, C.S., Hagen, M.F., Rubin, M.A., and Mello, C.F., Monosialoganglioside Increases Catalase Activity in Cerebral Cortex of Rats, Free Radic. Res., 2004, vol. 38, pp. 495–500.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    T. V. Sokolova, I. O. Zakharova, V. V. Furaev, M. P. Rychkova & N. F. Avrova

Authors
  1. T. V. Sokolova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. O. Zakharova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. V. Furaev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. P. Rychkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. F. Avrova
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Original Russian Text © T. V. Sokolova, I. O. Zakharova, V. V. Furaev, M. P. Rychkova, N. F. Avrova, 2008, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2008, Vol. 44, No. 1, pp. 26–31.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sokolova, T.V., Zakharova, I.O., Furaev, V.V. et al. PC12 cells transfected with human mutant gene causing one of Alzheimer’s disease forms have a high sensitivity to oxidative stress. J Evol Biochem Phys 44, 29–35 (2008). https://doi.org/10.1134/S0022093008010040

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093008010040

Key words

Search

Navigation