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Neurochemical Journal

, Volume 13, Issue 2, pp 156–163 | Cite as

The Proapoptotic Effect of Melatonin on the Functioning of the Nonspecific Mitochondrial Pore (mPTP) in Rat Mitochondria

  • Yu. L. BaburinaEmail author
  • I. V. Odinokova
  • O. V. Krestinina
Experimental Articles
  • 2 Downloads

Abstract

Melatonin (MEL) is a hormone produced by the pineal gland. It easily penetrates the cell membrane and may be accumulated in the mitochondria at high concentrations and improve their functional state. However, there are also data that show that the effect of MEL on mitochondria may greatly vary, i.e., it depends on the type of tissue, the conditions of administration, and the composition and structural features of the target molecules. In the present work, we studied the effect of MEL on the functional state of rat brain mitochondria when it is directly added to mitochondria under conditions of opening of the nonspecific mito-chondrial permeability transition pore (mPTP), as well as the effects on the levels of mPTP regulators (VDAC and CNPase) and the main subunits of the electron transport chain (ETC). It was found that the direct addition of MEL at a concentration of 10 nM and 100 nM to mitochondria leads to a change in the protein level of the first and fourth ETC complexes, initiation of mPTP opening, as well as a decrease in the levels of proteins that regulate mPTP function. These data suggest that MEL may act as a pro-apoptotic agent, which may have important biological and pharmacological significance.

Keywords

rat brain mitochondria melatonin non-specific mitochondrial permeability transition pore potential-dependent anion channel (VDAC) 2′,3′-cyclonucleotide-3′-phosphodiesterase (CNPase) 

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Notes

Acknowledgments

The equipment of Common Facilities Center of the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Science was used in the study.

References

  1. 1.
    Roopin, M. and Levy, O., J. Pineal Res., 2012, vol. 53, pp. 259–269.CrossRefGoogle Scholar
  2. 2.
    Migliori, M.L., Romanowski, A., Simonetta, S.H., Valdez, D., Guido, M., and Golombek, D.A., J. Pineal Res., 2012, vol. 53, pp. 38–46.CrossRefGoogle Scholar
  3. 3.
    Byeon, Y., Park, S., Kim, Y.S., Park, D.H., Lee, S., and Back, K., J. Pineal Res., 2012, vol. 53, pp. 107–111.CrossRefGoogle Scholar
  4. 4.
    Gomez, F.J., Raba, J., Cerutti, S., and Silva, M.F., J. Pineal Res., 2012, vol. 52, pp. 349–355.CrossRefGoogle Scholar
  5. 5.
    Stehle, J.H., Saade, A., Rawashdeh, O., Ackermann, K., Jilg, A., Sebesteny, T., and Maronde, E., J. Pineal Res., 2011, vol. 51, pp. 17–43.CrossRefGoogle Scholar
  6. 6.
    Slominski, A., Tobin, D.J., Zmijewski, M.A., Wortsman, J., and Paus, R., Trends Endocrinol. Metab., 2008, vol. 19, pp. 17–24.CrossRefGoogle Scholar
  7. 7.
    Morin, D., Simon, N., Depres-Brummer, P., Levi, F., Tillement, J.P., and Urien, S., Pharmacology, 1997, vol. 54, pp. 271–275.CrossRefGoogle Scholar
  8. 8.
    Pardridge, W.M. and Mietus, L.J., J. Neurochem., 1980, vol. 34, pp. 1761–1763.CrossRefGoogle Scholar
  9. 9.
    Cardinali, D.P., Lynch, H.J., and Wurtman, R.J., Endocrinology, 1972, vol. 91, pp. 1213–1218.CrossRefGoogle Scholar
  10. 10.
    Dubocovich, M.L., Delagrange, P., Krause, D.N., Sugden, D., Cardinali, D.P., and Olcese, J., Pharmacol. Rev., 2010, vol. 62, pp. 343–380.CrossRefGoogle Scholar
  11. 11.
    Dubocovich, M.L. and Markowska, M., Endocrine, 2005, vol. 27, pp. 101–110.CrossRefGoogle Scholar
  12. 12.
    Smirnov, A.N., Biochemistry (Moscow), 2001, vol. 66, pp. 19–26.Google Scholar
  13. 13.
    Becker-Andre, M., Wiesenberg, I., Schaeren-Wiemers, N., Andre, E., Missbach, M., Saurat, J.H., and Carlberg, C., J. Biol. Chem., 1994, vol. 269, pp. 28531–28534.Google Scholar
  14. 14.
    Kilic, U., Yilmaz, B., Ugur, M., Yuksel, A., Reiter, R.J., Hermann, D.M., and Kilic, E., J. Pineal Res., 2012, vol. 52, pp. 228–235.CrossRefGoogle Scholar
  15. 15.
    Reiter, R.J., Mayo, J.C., Tan, D.X., Sainz, R.M., Ala-torre-Jimenez, M., and Qin, L., J. Pineal Res., 2016, vol. 61, pp. 253–278.CrossRefGoogle Scholar
  16. 16.
    Miquel, J., Economos, A.C., Fleming, J., and Johnson, J.E., Jr, Exp. Gerontol., 1980, vol. 15, pp. 575–591.CrossRefGoogle Scholar
  17. 17.
    Papa, S. and Skulachev, V.P., Mol. Cell. Biochem., 1997, vol. 174, pp. 305–319.CrossRefGoogle Scholar
  18. 18.
    Acuna-Castroviejo, D., Escames, G., Leon, J., Carazo, A., and Khaldy, H., Adv. Exp. Med. Biol., 2003, vol. 527, pp. 549–557.CrossRefGoogle Scholar
  19. 19.
    Lopez, A., Garcia, J.A., Escames, G., Venegas, C., Ortiz, F., Lopez, L.C., and Acuna-Castroviejo, D., J. Pineal Res., vol. 46,no. 2. 2009, pp. 188–198.CrossRefGoogle Scholar
  20. 20.
    Cheshchevik, V.T., Dremza, I.K., Lapshina, E.A., Zabrodskaya, S.V., Kujawa, J., and Zavodnik, I.B., Cell Biochem. Funct., 2011, vol. 29, pp. 481–488.CrossRefGoogle Scholar
  21. 21.
    Zavodnik, I.B., Lapshina, E.A., Cheshchevik, V.T., Dremza, I.K., Kujawa, J., Zabrodskaya, S.V., and Reiter, R.J., J. Physiol. Pharmacol., 2011, vol. 62, pp. 421–427.Google Scholar
  22. 22.
    Cheshchevik, V.T., Lapshina, E.A., Dremza, I.K., Zabrodskaya, S.V., Reiter, R.J., Prokopchik, N.I., and Zavodnik, I.B., Toxicol. Appl. Pharmacol., 2012, vol. 261, pp. 271–279.CrossRefGoogle Scholar
  23. 23.
    Petrosillo, G., Casanova, G., Matera, M., Ruggiero, F.M., and Paradies, G., FEBS Lett., 2006, vol. 580, pp. 6311–6316.CrossRefGoogle Scholar
  24. 24.
    Martin, M., Macias, M., Escames, G., Leon, J., and Acuna-Castroviejo, D., FASEB J., 2000, vol. 14, pp. 1677–1679.CrossRefGoogle Scholar
  25. 25.
    Halestrap, A., Nature, 2005, vol. 434, pp. 578–579.CrossRefGoogle Scholar
  26. 26.
    Jou, M.J., J. Pineal Res., 2011, vol. 50, pp. 427–435.CrossRefGoogle Scholar
  27. 27.
    Krestinina, O.V., Baburina, Y.L., and Azarashvili, T.S., Biol. Membrany, 2014, vol. 31, pp. 95–103.CrossRefGoogle Scholar
  28. 28.
    Baburina, Y., Odinokova, I., Azarashvili, T., Akatov, V., Lemasters, J.J., and Krestinina, O., Bba-Biomem-branes, 2017, vol. 1859, pp. 94–103.CrossRefGoogle Scholar
  29. 29.
    Martinis, P., Zago, L., Maritati, M., Battaglia, V., Grancara, S., Rizzoli, V., Agostinelli, E., Bragadin, M., and Toninello, A., Amino Acids, 2012, vol. 42, pp. 1827–1837.CrossRefGoogle Scholar
  30. 30.
    Bejarano, I., Redondo, P.C., Espino, J., Rosado, J.A., Paredes, S.D., Barriga, C., Reiter, R.J., Pariente, J.A., and Rodriguez, A.B., J. Pineal Res., 2009, vol. 46, pp. 392–400.CrossRefGoogle Scholar
  31. 31.
    Osseni, R.A., Rat, P., Bogdan, A., Warnet, J.M., and Touitou, Y., Life Sci., 2000, vol. 68, pp. 387–399.CrossRefGoogle Scholar
  32. 32.
    Sims, N.R., J. Neurochem., 1990, vol. 55, pp. 698–707.CrossRefGoogle Scholar
  33. 33.
    Stricker, R., Lottspeich, F., and Reiser, G., Biol. Chem. Hoppe Seyler, 1994, vol. 375, pp. 205–209.Google Scholar
  34. 34.
    Tan, D.X., Manchester, L.C., Reiter, R.J., Plummer, B.F., Limson, J., Weintraub, S.T., and Qi, W., Free Radic. Biol. Med., 2000, vol. 29, pp. 1177–1185.CrossRefGoogle Scholar
  35. 35.
    Acuna-Castroviejo, D., Martin, M., Macias, M., Escames, G., Leon, J., Khaldy, H., and Reiter, R.J., J. Pineal Res., 2001, vol. 30, pp. 65–74.CrossRefGoogle Scholar
  36. 36.
    Martin, M., Macias, M., Leon, J., Escames, G., Khaldy, H., and Acuna-Castroviejo, D. Int. J. Bio-chem. Cell Biol., 2002, vol. 34, pp. 348–357.CrossRefGoogle Scholar
  37. 37.
    Odinokova, I., Baburina, Yu., Kruglov, A., Fadeeva, I., Zvyagina, A., Sotnikova, L., Akatov, V., and Krestinina, O., Int. J. Mol. Sci., 2018, vol. 19, pp. 1–16.CrossRefGoogle Scholar
  38. 38.
    Buyukavci, M., Ozdemir, O., Buck, S., Stout, M., Ravindranath, Y., and Savasan, S., Fundam. Clin. Pharmacol., 2006, vol. 20, pp. 73–79.CrossRefGoogle Scholar
  39. 39.
    Srinivasan, V., Spence, D.W., Pandi-Perumal, S.R., Trakht, I., and Cardinali, D.P., Integr. Cancer Ther., 2008, vol. 7, pp. 189–203.CrossRefGoogle Scholar
  40. 40.
    Hou, T., Zhang, X., Xu, J., Jian, C., Huang, Z., Ye, T., Hu, K., Zheng, M., Gao, F., Wang, X., and Cheng, H., J. Biol. Chem., 2013, vol. 288, pp. 4602–4612.CrossRefGoogle Scholar
  41. 41.
    Ma, Q., Fang, H., Shang, W., Liu, L., Xu, Z., Ye, T., Wang, X., Zheng, M., Chen, Q., and Cheng, H., J. Biol. Chem., 2011, vol. 286, pp. 27573–27581.CrossRefGoogle Scholar
  42. 42.
    Baburina, Y., Azarashvili, T., Grachev, D., Krestinina, O., Galvita, A., Stricker, R., and Reiser, G., Neurochemis-try International, 2015, vol. 90, pp. 46–55.CrossRefGoogle Scholar
  43. 43.
    Azarashvili, T., Krestinina, O., Galvita, A., Grachev, D., Baburina, Y., Stricker, R., Evtodienko, Y., and Reiser, G., Am. J. Physiol. Cell Physiol., 2009, vol. 296, pp. C1428–C1439.CrossRefGoogle Scholar
  44. 44.
    Krestinina, O., Azarashvili, T., Baburina, Y., Galvita, A., Grachev, D., Stricker, R., and Reiser, G., Neurochem-istry Int., 2015, vol. 80, pp. 41–50.CrossRefGoogle Scholar
  45. 45.
    Baburina, Y., Azarashvili, T., Grachev, D., Krestinina, O., Galvita, A., Stricker, R., and Reiser, G., Neurochem. Int., 2015, vol. 90, pp. 46–55.CrossRefGoogle Scholar
  46. 46.
    Azarashvili, T., Stricker, R., and Reiser, G., Biol. Chem., 2010, vol. 391, pp. 619–629.CrossRefGoogle Scholar
  47. 47.
    Baines, C.P., Kaiser, R.A., Sheiko, T., Craigen, W.J., and Molkentin, J.D., Nat. Cell Biol., 2007, vol. 9, pp. 550–555.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • Yu. L. Baburina
    • 1
    Email author
  • I. V. Odinokova
    • 1
  • O. V. Krestinina
    • 1
  1. 1.Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchino, Moscow oblast’Russia

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