Neurochemical Journal

, Volume 12, Issue 1, pp 111–116 | Cite as

The Dependence of the Protective Effect of Insulin on Its Concentration and Modulation of ERK1/2 Activity under the Conditions of Oxidative Stress in Cortical Neurons

  • I. I. Zorina
  • L. V. Bayunova
  • I. O. Zakharova
  • N. F. AvrovaEmail author
Short Communications


It has been recently shown that insulin has a neuroprotective effect. Experimental studies and clinical trials have demonstrated that insulin is a promising drug for treatment of neurodegenerative and other diseases associated with brain damage. However, the mechanism of the neuroprotective effect of insulin is far from being elucidated. The aim of this study was to examine the dependence of the protective effect of insulin in cortical neurons on its concentration and the involvement of the modulation of the activity of extracellular signal-regulated kinase (ERK1/2) by insulin in neuronal survival. Using the MTT method, we found that the protective effect of insulin in neurons treated with hydrogen peroxide varied in the concentration range of 1–100 nm (1 nM < 10 nM < 100 nM). There were no significant differences between the effects of 100 nM or 1 nM insulin. The literature data on the effects of insulin on the activity of ERK1/2 in neurons are controversial. We studied the modulatory effect of insulin on the activity of ERK1/2 in cortical neurons during development of oxidative stress using the immunoblotting method at eight time points after prooxidant application. We found that insulin increased the basal activity of ERK1/2 and the activity of the enzyme at the early stage of action of hydrogen peroxide, that is, 5–30 min after its addition. This may improve the protective effect of insulin.


cortical neurons oxidative stress insulin protective effect ERK1/2 activation 


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  1. 1.
    Miller, E.R., Pastor-Barriuso, R., Dalal, D., Riemersma, R., Appel, L.J., and Guallar, E., Ann. Intern. Med., 2005, vol. 142, pp. 37–46.CrossRefPubMedGoogle Scholar
  2. 2.
    Bjelakovic, G., Nikolova, D., Gluud, L.L., Simonetti, R.G., and Gluud, C., J. Amer. Med. Association, 2007, vol. 297, pp. 842–857.CrossRefGoogle Scholar
  3. 3.
    Bjelakovic, G., Nikolova, D., and Gluud, C., PLoS One, 2013, vol. 8, no. 9: e74558.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Duarte, A.I., Santos, P., Oliveira, C.R., Santos, M.S., and Rego, A.C., Biochim. Biophys. Acta, 2008, vol. 1783, pp. 994–1002.CrossRefPubMedGoogle Scholar
  5. 5.
    Ramalingam, M. and Kim, S.J., J. Recept. Signal Transduct., Res., 2015, vol. 35, pp. 1–7.CrossRefGoogle Scholar
  6. 6.
    Sukhov, I.B., Shipilov, V.N., Chistyakova, O.V., Trost, A.M., and Shpakov, A.O., Dokl. Akad. Nauk, 2013, vol. 453, no. 5, pp. 577–580.Google Scholar
  7. 7.
    Shpakov, A.O., Derkach, K.V., and Berstein, L.M., Future Science OA (FSO), 2015, vol. 1, no. 3: FSO25. doi 10.4155/fso.15.23Google Scholar
  8. 8.
    Claxton, A., Baker, L.D., Hanson, A., Trittschuh, E.H., Cholerton, B., Morgan, A., Callaghan, M., Arbuckle, M., Behl, C., and Craft, S., J. Alzheimer’s Dis., vol. 44, no. 3, pp. 897–906.Google Scholar
  9. 9.
    Shah, A.K., Gupta, A., and Dey, C.S., AICAR Arch. Biochem. Biophys., 2011, vol. 509, pp. 142–146.CrossRefPubMedGoogle Scholar
  10. 10.
    Dichter, M.A., Brain Res., 1978, vol. 149, pp. 279–293.CrossRefPubMedGoogle Scholar
  11. 11.
    Mironova, E.V., Evstratova, A.A., and Antonov, S.M., J. Neurosci. Methods, 2007, vol. 163, pp. 1–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Hansen, M.B., Nielsen, S.E., and Berg, K.J., Immunol. Methods, 1989, vol. 119, pp. 203–210.CrossRefGoogle Scholar
  13. 13.
    Zakharova, I.O., Sokolova, T.V., Bayunova, L.V., Vlasova, Y.A., Rychkova, M.P., and Avrova, N.F., Int. J. Mol. Sci., 2012, vol. 13, pp. 11543–11668.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Duarte, A.I., Santos, M.S., Oliveira, C.R., and Rego, A.C., Free Rad. Biol. Med., 2005, vol. 39, pp. 876–889.CrossRefPubMedGoogle Scholar
  15. 15.
    Ryu, B.R., Ko, H.W., Jou, I., Noh, J.S., and Gwag, B.J., J. Neurobiol., 1999, vol. 39, pp. 536–546.CrossRefPubMedGoogle Scholar
  16. 16.
    Hui, L., Pei, D.-S., Zhang, Q.-G., Guan, Q.-H., and Zhang, G.-Y., Brain Res., 2005, vol. 1052, pp. 1–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Kim, L., Pei, D.-S., Zhang, Q-G., Guan, Q.-H., and Zhang, G.-Y., Antioxid. Redox Sign., 2011, vol. 14, pp. 1829–1839.CrossRefGoogle Scholar
  18. 18.
    Sui, Z., Kovacs, A.D., and Maggirwar, S.B., Biochem. Biophys. Res. Commun., 2006, vol. 345, pp. 1643–1648.CrossRefPubMedGoogle Scholar
  19. 19.
    Filippi, B.M., Yang, C.S., Tang, C., and Lam, T.K., Cell Metab., 2012, vol. 16, pp. 500–510.CrossRefPubMedGoogle Scholar
  20. 20.
    Kong, D., Gong, L., Arnold, E., Shanmugam, S., Fort, P.E., Gardner, T.W., and Abcouwer, S.F., Exp. Eye Res., 2015, vol. 151, pp. 83–95.Google Scholar
  21. 21.
    Ziegler, C.G., Sicard, F., Sperber, S., Ehrhart-Bornstein, M., Bornstein, S.R., and Krug, A.W., Ann. NY Acad. Sci., 2006, vol. 1073, pp. 306–311.CrossRefPubMedGoogle Scholar
  22. 22.
    Vauzour, D., Vafeiadou K., Rice-Evans, C., Williams, R.J., and Spencer, J.P, J. Neurochem., 2007, vol. 103, pp. 1355–1367.CrossRefPubMedGoogle Scholar
  23. 23.
    Zakharova, I.O., Sokolova, T.V., Vlasova, Y.A., Furaev, V.V., Rychkova, M.P., and Avrova, N.F., Neurochem. Res., 2014, vol. 39, pp. 2262–2275.CrossRefPubMedGoogle Scholar
  24. 24.
    Namura, S., Iihara, K., Takami, S., Nagata, I., Kikuchi, H., Matsushita, K., Moskowitz, M.A., Bonventre, J.V., and Alessandrini, A., Proc. Natl. Acad. Sci. U.S.A., 2001, vol. 98, pp. 11569–11574.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lu, K., Liang, C.L., Liliang, P.C., Yang, S.-H., Cho, C.L., Weng, H.C., Tsai, Y.-D., Wang, K.W., and Chen, H.J., J. Neurochem., 2010, vol. 114, pp. 237–246.PubMedGoogle Scholar
  26. 26.
    Zakharova, I.O., Sokolova, T.V., Vlasova, Y.A., Bayunova, L.V., Rychkova, M.P., and Avrova, N.F, Int. J. Mol. Sci., 2017, vol. 18, no. 1:216.CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Kulebyakin, K., Karpova, L., Lakonsteva, E., Krasavin, M., and Boldyrev, A., Amino Acids, 2012, vol. 43, pp. 91–96.CrossRefPubMedGoogle Scholar
  28. 28.
    Luo, Y. and DeFranco, D.B., J. Biol. Chem., 2006, vol. 281, pp. 16436–16442.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • I. I. Zorina
    • 1
  • L. V. Bayunova
    • 1
  • I. O. Zakharova
    • 1
  • N. F. Avrova
    • 1
    • 2
    Email author
  1. 1.Sechenov Institute of Evolutionary Physiology and BiochemistrySt. PetersburgRussia
  2. 2.St. PetersburgRussia

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