Biochemistry (Moscow)

, Volume 78, Issue 1, pp 75–79 | Cite as

Mechanism of induction of oxidative stress in liver mitochondria by low concentrations of tert-butyl hydroperoxide

  • N. I. FedotchevaEmail author
  • E. N. Mokhova


The mechanism of the effect of tert-butyl hydroperoxide (tBHP) on the kinetics of decrease in liver mitochondrial ΔΨ (transmembrane electric potential) in response to successive additions of tBHP in low concentrations has been studied. FeSO4 was found to increase significantly the damaging effect of tBHP; this effect was shown to increase in the presence of low concentrations of Ca2+ starting from 2 μM CaCl2. Cyclosporin A prevents these effects. The data show that the damaging effect of low concentrations of tBHP in the course of pyruvate oxidation in isolated liver mitochondria is caused by the opening of the nonspecific Ca2+-dependent cyclosporin A-sensitive pore in the inner mitochondrial membrane. Application of a method of studying oxidative stress regulators, developed in this work, is illustrated by an example of the prooxidant action of ascorbate. This method is proposed for studying mitochondria in hemochromatosis, a pathology caused by excessive accumulation of iron.

Key words

oxidative stress liver mitochondria tert-butyl hydroperoxide pyruvate cyclosporin A-sensitive pore hemochromatosis 



tert-butyl hydroperoxide


transmembrane difference of electric potentials on the inner mitochondrial membrane


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  1. 1.
    Boveris, A., and Chance, B. (1973) Biochem. J., 134, 707–716.PubMedGoogle Scholar
  2. 2.
    Chance, B., Sies, H., and Boveris, A. (1979) Physiol. Rev., 59, 527–605.PubMedGoogle Scholar
  3. 3.
    Starke, P. E., and Farber, J. L. (1985) J. Biol. Chem., 260, 10099–10104.PubMedGoogle Scholar
  4. 4.
    Haidara, K., Marion, M., Gascon-Barre, M., Denizeau, F., and Averill-Bates, D. A. (2008) Toxicol. Appl. Pharmacol., 229, 65–76.PubMedCrossRefGoogle Scholar
  5. 5.
    Lemasters, J. J., Nieminen, A. L., Qian, T., Trost, L. C., Elmore, S. P., Nishimura, Y., Crowe, R. A., Cascio, W. E., Bradham, C. A., Brenner, D. A., and Herman, B. (1998) Biochim. Biophys. Acta, 1366, 177–196.PubMedCrossRefGoogle Scholar
  6. 6.
    Beatrice, M. C., Stiers, D. L., and Pfeiffer, D. R. (1982) J. Biol. Chem., 257, 7161–7671.PubMedGoogle Scholar
  7. 7.
    Chen, X., Zhang, J., Fang, Y., Zhao, C., and Zhu, Y. (2008) Gerontol. A Biol. Sci. Med. Sci., 63, 253–264.CrossRefGoogle Scholar
  8. 8.
    Hibaoui, Y., Roulet, E., and Ruegg, U. T. (2009) J. Pineal. Res., 47, 238–252.PubMedCrossRefGoogle Scholar
  9. 9.
    Martin, M., Macias, M., Escames, G., Leon, J., and Acuna-Castroviejo, D. (2000) FASEB J., 14, 1677–1679.PubMedGoogle Scholar
  10. 10.
    Endlicher, R., Krivakova, P., Rauchova, H., Nuskova, H., Cervinkova, Z., and Drahota, Z. (2009) Physiol. Res., 58, 685–692.PubMedGoogle Scholar
  11. 11.
    Cervinkova, Z., Krivakova, P., Labajova, A., Rousar, T., Lotkova, H., Kucera, O., Endlicher, R., Cervinka, M., and Drahota, Z. (2009) Arch. Toxicol., 83, 63–72.Google Scholar
  12. 12.
    Cervinkova, Z., Lotkova, H., Krivakova, P., Rousar, T., Kucera, O., Tichy, L., Cervinka, M., and Drahota, Z. (2007) Altern. Lab. Anim., 35, 353–361.PubMedGoogle Scholar
  13. 13.
    Siegel, S. (1956) Nonparametric Statistics for the Behavioral Sciences (McGraw-Hill Series in Psychology), N.Y.Google Scholar
  14. 14.
    Brailovskaya, I. V., Starkov, A. A., and Mokhova, E. N. (2001) Biochemistry (Moscow), 66, 909–912.CrossRefGoogle Scholar
  15. 15.
    Khailova, L. S., Dedukhova V. I., and Mokhova, E. N. (2008) Biochemistry (Moscow), 73, 1121–1124.CrossRefGoogle Scholar
  16. 16.
    Almeida, A. M., Bertoncini, C. R., Borecky, J., Souza-Pinto, N. C., and Vercesi, A. E. (2006) An. Acad. Bras. Cienc., 78, 505–514.PubMedCrossRefGoogle Scholar
  17. 17.
    Britton, R. S., Leicester, K. L., and Bacon, B. R. (2002) Int. J. Hematol., 76, 219–228.PubMedCrossRefGoogle Scholar
  18. 18.
    Mokhova, E. N. (2011) Biophys. Rev. Lett., 6, 1–13.CrossRefGoogle Scholar
  19. 19.
    Giron-Calle, J., and Schmid, H. H. (1996) Biochemistry, 35, 15440–15446.PubMedCrossRefGoogle Scholar
  20. 20.
    Kowaltowski, A. J., Vercesi, A. E., and Castilho, R. F. (1997) Biochim. Biophys. Acta, 1318, 395–402.PubMedCrossRefGoogle Scholar
  21. 21.
    Fedotcheva, N. I., Sokolov, A. P., and Kondrashova, M. N. (2006) Free Radic. Biol. Med., 41, 56–64.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  1. 1.Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchino, Moscow RegionRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Research Institute of MitoengineeringLomonosov Moscow State UniversityMoscowRussia

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