Advertisement

Biochemistry (Moscow)

, Volume 75, Issue 5, pp 598–605 | Cite as

Acetoacetate as regulator of palmitic acid-induced uncoupling involving liver mitochondrial ADP/ATP antiporter and aspartate/glutamate antiporter

  • V. N. SamartsevEmail author
  • O. V. Kozhina
Article

Abstract

The effect of acetoacetate on palmitate-induced uncoupling with the involvement of ADP/ATP antiporter and aspartate/glutamate antiporter has been studied in liver mitochondria. The incubation of mitochondria with acetoacetate during succinate oxidation in the presence of rotenone, oligomycin, and EGTA suppresses the accumulation of conjugated dienes. This is considered as a display of antioxidant effect of acetoacetate. Under these conditions, acetoacetate does not influence the respiration of mitochondria in the absence or presence of palmitate but eliminates the ability of carboxyatractylate or aspartate separately to suppress the uncoupling effect of this fatty acid. The action of acetoacetate is eliminated by β-hydroxybutyrate or thiourea, but not by the antioxidant Trolox. In the absence of acetoacetate, the palmitate-induced uncoupling is limited by a stage sensitive to carboxyatractylate (ADP/ATP antiporter) or aspartate (aspartate/glutamate antiporter); in its presence, it is limited by a stage insensitive to the effect of these agents. In the presence of Trolox, ADP suppresses the uncoupling action of palmitate to the same degree as carboxyatractylate. Under these conditions, acetoacetate eliminates the recoupling effects of ADP and aspartate, including their joint action. This effect of acetoacetate is eliminated by β-hydroxybutyrate or thiourea. It is supposed that the stimulating effect of acetoacetate is caused both by increase in the rate of transfer of fatty acid anion from the inner monolayer of the membrane to the outer one, which involves the ADP/ATP antiporter and aspartate/glutamate antiporter, and by elimination of the ability of ADP to inhibit this transport. Under conditions of excessive production of reactive oxygen species in mitochondria at a high membrane potential and in the presence of small amounts of fatty acids, such effect of acetoacetate can be considered as one of the mechanisms of antioxidant protection.

Key words

liver mitochondria acetoacetate fatty acids uncoupling ADP/ATP antiporter aspartate/glutamate antiporter 

Abbreviations

ROS

reactive oxygen species

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bra, M., Quinan, B., and Suzin, S. A. (2005) Biochemistry (Moscow), 70, 231–239.CrossRefGoogle Scholar
  2. 2.
    Zorov, D. B., Isayev, N. K., Plotnikov, E. Yu., Zorova, L. D., Stel’mashchuk, E. V., Vasilyeva, A. K., Arkhangel’skaya, A. A., and Khryapenkova, T. G. (2007) Biochemistry (Moscow), 72, 1115–1126.CrossRefGoogle Scholar
  3. 3.
    Rasola, A., and Bernardi, P. (2007) Apoptosis, 12, 815–833.CrossRefPubMedGoogle Scholar
  4. 4.
    Skulachev, V. P. (2006) Apoptosis, 11, 473–485.CrossRefPubMedGoogle Scholar
  5. 5.
    Brand, M. D., Affourtit, C., Esteves, T. C., Green, K., Lambert, A. J., Miwa, S., Pakay, J. L., and Parker, N. (2004) Free Rad. Biol. Med., 37, 755–767.CrossRefPubMedGoogle Scholar
  6. 6.
    Andreev, A. Yu., Kushnareva, Yu. E., and Starkov, A. A. (2005) Biochemistry (Moscow), 70, 200–214.CrossRefGoogle Scholar
  7. 7.
    Echtay, K. S. (2007) Free Rad. Biol. Med., 43, 1351–1371.CrossRefPubMedGoogle Scholar
  8. 8.
    Echtay, K. S., Esteves, T. C., Pakay, J. L., Jekabsons, M. B., Lambert, A. J., Portero-Otin, M., Pamplona, R., Vidal-Puig, A. J., Wang, S., Roebuck, S. J., and Brand, M. D. (2003) EMBO J., 22, 4103–4110.CrossRefPubMedGoogle Scholar
  9. 9.
    Skulachev, V. P. (1998) Biochim. Biophys. Acta, 1363, 100–124.CrossRefPubMedGoogle Scholar
  10. 10.
    Lenaz, G. (1998) Biochim. Biophys. Acta, 1366, 53–67.CrossRefPubMedGoogle Scholar
  11. 11.
    Korshunov, S. S., Korkina, O. V., Ruuge, E. K., Skulachev, V. P., and Starkov, A. A. (1998) FEBS Lett., 435, 215–218.CrossRefPubMedGoogle Scholar
  12. 12.
    Samartsev, V. N., Smirnov, A. V., Zeldi, I. P., Markova, O. V., Mokhova, E. N., and Skulachev, V. P. (1997) Biochim. Biophys. Acta, 1339, 251–257.Google Scholar
  13. 13.
    Mokhova, E. N., and Khaylova, L. S. (2005) Biochemistry (Moscow), 70, 159–163.CrossRefGoogle Scholar
  14. 14.
    Samartsev, V. N., and Kozhina, O. V. (2008) Biochemistry (Moscow), 73, 783–790.CrossRefGoogle Scholar
  15. 15.
    Kozhina, O. V., Karatetskova, M. P., and Samartsev, V. N. (2006) Biol. Membr. (Moscow), 23, 213–218.Google Scholar
  16. 16.
    Samartsev, V. N., Kozhina, O. V., and Polishchuk, L. S. (2008) Abstr. IV Congr. Russ. Soc. of Biochemists and Molecular Biologists, May 11–15, 2008, Novosibirsk, p. 336.Google Scholar
  17. 17.
    Azzu, V., Parker, N., and Brand, M. (2008) Biochem. J., 413, 323–332.CrossRefPubMedGoogle Scholar
  18. 18.
    Esterbauer, H. (1993) Am. J. Clin. Nutr., 57, 779S–785S.PubMedGoogle Scholar
  19. 19.
    Yang, Y., Sharma, R., Sharma, A., Awasthi, S., and Awasthi, Y. C. (2003) Acta Biochim. Pol., 50, 319–336.PubMedGoogle Scholar
  20. 20.
    Raza, H., John, A., Brown, E. M., Benedict, S., and Kambai, A. (2008) Toxicol. Appl. Pharmacol., 226, 161–168.CrossRefPubMedGoogle Scholar
  21. 21.
    Chen, J., Schenker, S., Frosto, T. A., and Henderson, G. I. (1998) Biochim. Biophys. Acta, 1380, 336–344.PubMedGoogle Scholar
  22. 22.
    Patel, V. B., Spencer, C. H., Young, T. A., Lively, M. O., and Cunningham, C. C. (2007) Free Rad. Biol. Med., 43, 1499–1507.CrossRefPubMedGoogle Scholar
  23. 23.
    McGarry, J. D., and Foster, D. W. (1980) Annu. Rev. Biochem., 49, 395–420.CrossRefPubMedGoogle Scholar
  24. 24.
    Hegardt, F. G. (1999) Biochem. J., 338, 569–582.CrossRefPubMedGoogle Scholar
  25. 25.
    Pires, J., Curi, R., and Otton, R. (2007) Clin. Sci., 112, 59–67.CrossRefPubMedGoogle Scholar
  26. 26.
    Massieu, L., Haces, M. L., Montiel, T., and Hernandez-Fonseca, K. (2003) Neuroscience, 120, 365–378.CrossRefPubMedGoogle Scholar
  27. 27.
    Squires, J. E., Sun, J., Caffrey, J. L., Yoshishige, D., and Mallet, R. T. (2003) Am. J. Physiol. Heart Circ. Physiol., 284, H1340–H1347.PubMedGoogle Scholar
  28. 28.
    Maalouf, M., Sullivan, P. G., Davis, L., Kim, D. Y., and Rho, J. M. (2007) Neuroscience, 145, 256–264.CrossRefPubMedGoogle Scholar
  29. 29.
    Bindoli, A., Callegaro, M. T., Barzon, E., Benetti, M., and Rigobello, M. P. (1997) Arch. Biochem. Biophys., 342, 22–28.CrossRefPubMedGoogle Scholar
  30. 30.
    Costantini, P., Chernyak, B. V., Petronilli, V., and Bernardi, P. (1996) J. Biol. Chem., 271, 6746–6751.CrossRefPubMedGoogle Scholar
  31. 31.
    Le-Quoc, E. D., and Le-Quoc, K. (1989) Arch. Biochem. Biophys., 273, 466–478.CrossRefPubMedGoogle Scholar
  32. 32.
    Hinkle, P. C., and Yu, M. L. (1979) J. Biol. Chem., 254, 2450–2455.PubMedGoogle Scholar
  33. 33.
    Kozhina, O. V., Stepanova, L. A., and Samartsev, V. N. (2007) Biol. Membr. (Moscow), 24, 421–429.Google Scholar
  34. 34.
    Ambrosio, G., Flaherty, J. T., Duilio, C., Tritto, I., Santoro, G., Elia, P. P., Condorelli, M., and Chiariello, M. (1991) J. Clin. Invest., 87, 2056–2066.CrossRefPubMedGoogle Scholar
  35. 35.
    Slater, T. F. (1984) Biochem. J., 222, 1–15.PubMedGoogle Scholar
  36. 36.
    Kushnareva, Y., Murphy, A. N., and Andreyev, A. (2002) Biochem. J., 368, 545–553.CrossRefPubMedGoogle Scholar
  37. 37.
    Wojtczak, L., and Schonfeld, P. (1993) Biochim. Biophys. Acta, 1183, 41–57.CrossRefPubMedGoogle Scholar
  38. 38.
    Samartsev, V. N., Markova, O. V., Zeldi, I. P., and Smirnov, A. V. (1999) Biochemistry (Moscow), 64, 901–911.Google Scholar
  39. 39.
    Samartsev, V. N., Mokhova, E. N., and Skulachev, V. P. (1997) FEBS Lett., 412, 179–182.CrossRefPubMedGoogle Scholar
  40. 40.
    Doson, R., Elliot, D., Elliot, U., and Jones, K. (1991) Biochemist’s Handbook [Russian translation], Mir, Moscow.Google Scholar
  41. 41.
    Davies, M. J., Forni, L. G., and Willson, R. L. (1988) Biochem. J., 255, 513–522.PubMedGoogle Scholar
  42. 42.
    Majima, E., Koike, H., Hong, Y.-M., Shinohara, Y., and Terada, H. (1993) J. Biol. Chem., 268, 22181–22187.PubMedGoogle Scholar
  43. 43.
    Dierks, T., Salentin, A., Heberger, C., and Kramer, R. (1990) Biochim. Biophys. Acta, 1028, 268–280.CrossRefPubMedGoogle Scholar
  44. 44.
    Bohnensack, R., Kuster, U., and Letko, G. (1982) Biochim. Biophys. Acta, 680, 271–280.CrossRefPubMedGoogle Scholar
  45. 45.
    Groen, A. K., Wanders, R. J., Westerhoff, H. V., van der Meer, R., and Tager, J. M. (1982) J. Biol. Chem., 257, 2754–2757.PubMedGoogle Scholar
  46. 46.
    Veech, R. L., Lawson, J. W. R., Cornell, N. W., and Krebs, H. A. (1979) J. Biol. Chem., 254, 6538–6547.PubMedGoogle Scholar
  47. 47.
    Schwenke, W. D., Soboll, S., Seitz, H. J., and Sies, H. (1981) Biochem., J., 200, 405–408.Google Scholar
  48. 48.
    Andreyev, A. Yu., Bondareva, T. O., Dedukhova, V. I., Mokhova, E. N., Skulachev, V. P., Tsofina, L. M., Volkov, N. I., and Vygodina, T. V. (1989) Eur. J. Biochem., 182, 585–592.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  1. 1.Mari State UniversityYoshkar-OlaRussia

Personalised recommendations