Skip to main content
SpringerLink
Log in

Inhibition of Ca-induced calcium release from mitochondria by antiischemic phenol-based antioxidants

  • Published:
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Effects of different inhibitors of lipid peroxidation (LP), such as sulphur-containing oligoquinone hypoxen, natural flavonoid dihydroquercetin (DHQ), and β-ionol, on Ca2+-induced calcium release from rat liver mitochondria (RLM) were investigated during oxidation of various substrates. The hypothesis about interrelation between antioxidant properties and influence of selected substances on spontaneous calcium release from mitochondria was verified. Degree of antioxidant activity of the selected substances was estimated by the inhibition of LP induced by Fe2+/ATP complex in phospholipid emulsion or in rat liver mitochondria (RLM). According to the inhibition efficacy the investigated substances were ordered as follows: β-ionol ≫ hypoxen > DHQ. 50% inhibition of oxygen consumption during LP of phospholipid emulsion was reached in presence of 3.2 ± 0.6 μM of β-ionol, 15.0 ± 1.1 μM of hypoxen, or 19.8 ± 1.7 μM of DHQ. Among the investigated antioxidants hypoxen only decreased spontaneous release of calcium from RLM after calcium accumulation by RLM. The impact of the antioxidants onto calcium current depended on the oxidized substrate. Hypoxen effect was most expressed during the oxidation of NAD-dependent substrate. The direct relationship between the antioxidant activity of the selected antioxidants and their influence on calcium transport in RLM was not revealed. The results indicate that the choice of antiischemic preparations should not only rely on their antioxidant activities.

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

Abbreviations

Mt:

mitochondria

MPTP:

mitochondrial permeability transition pore

RLM:

rat liver mitochondria

LP:

lipid peroxidation

DHQ:

dihydroquercetin

mCICR:

Ca2+-induced calcium release from mitochondria

Suc:

succinate

Glu:

glutamate

HB:

3-hydroxybutirate

OG:

2-oxoglutarate

Mal:

malate

References

  1. Crompton, M., The Mitochondrial Permeability Transition Pore and Its Role in Cell Death, Biochem. J., 1999, vol. 341, pp. 233–249.

    Article  PubMed  CAS  Google Scholar 

  2. Bernardi, P., Mitochondrial Transport of Cations: Channels, Exchangers, and Permeability Transition, Physiol. Rev., 1999, vol. 79, pp. 1127–1155.

    PubMed  CAS  Google Scholar 

  3. Zoratti, M. and Szabo, I., The Mitochondrial Permeability Transition, Biochim. Biophys. Acta, 1995, vol. 1241, no. 2, pp. 139–176.

    PubMed  Google Scholar 

  4. Green, D.R. and Kroemer, G., The Pathophysiology of Mitochondrial Cell Death, Science, 2004, vol. 305, pp. 626–629.

    Article  PubMed  CAS  Google Scholar 

  5. Weiss, J.N., Korge, P., Honda, H.M., and Ping, P., Role of the Mitochondrial Permeability Transition in Myocar dial Disease, Circulation Research, 2003, vol. 93, pp. 292–301.

    Article  PubMed  CAS  Google Scholar 

  6. Di Lisa, F. and Bernardi, P., Mitochondrial Function and Myocardial Aging. A Critical Analysis of the Role of Permeability Transition, Cardiovasc. Res., 2005, vol. 66, pp. 222–232.

    Article  PubMed  CAS  Google Scholar 

  7. Greene, E.L. and Paller, M.S., Calcium and Free Radicals in Hypoxia/Reoxygenation Injury of Renal Epithelial Cells, Am. J. Physiol. Renal Physiol., 1994, vol. 266, pp. F13–F20.

    CAS  Google Scholar 

  8. Richter, C. and Kass, G.E.N., Oxidative Stress in Mitochondria: Its Relationship to Cellular Ca2+ Homeostasis, Cell Death, Proliferation, and Differentiation, Chem. Biol. Interaction, 1991, vol. 77, pp. 1–23.

    Article  CAS  Google Scholar 

  9. Ganitkevich, V.Y., The Role of Mitochondria in Cytoplasmic Ca2+ Cycling, Exp. Physiol., 2003, vol. 88, pp. 91–97.

    Article  PubMed  CAS  Google Scholar 

  10. Chien, K.R., Han, A., Sen, A., Buja, L.M., and Willerson, J.T., Accumulation of Unesterified Arachidonic Acid in Ichemic Canine Myocardium. Relationship to a Phosphatidylcholine Deacylation-Reacylation Cycle and the Depletion of Membrane Phospholipids, Circ. Res., 1984, vol. 54, pp. 313–322.

    PubMed  CAS  Google Scholar 

  11. Portilla, D., Mandel, L.J., Bar-Sagi, D., and Millington, D.S., Anoxia Induces Phospholipase A2 Activation in Rabbit Renal Proximal Tubules, Am. J. Physiol., 1992, vol. 262, pp. F354–F360.

    PubMed  CAS  Google Scholar 

  12. Das, D.K., Engelman, R.M., Rousou, J.A., et al., Role of Membrane Phospholipids in Myocardial Injury Induced by Ischemia and Reperfusion, Am. J. Physiol., 1986, vol. 251, no. 20, pp. H71–H79.

    PubMed  CAS  Google Scholar 

  13. Kowaltowski, A.J., Castilho, R.F., and Vercesi, A.E., Mitochondrial Permeability Transition and Oxidative Stress, FEBS Lett., 2001, vol. 495, nos. 1–2, pp. 12–15.

    Article  PubMed  CAS  Google Scholar 

  14. Vercesi, A.E., Kowaltowski, A.J., Oliveira, H.C., and Castilho, R.F., Mitochondrial Ca2+ Transport, Permeability Transition and Oxidative Stress in Cell Death: Implications in Cardiotoxicity, Neurodegeneration and Dyslipidemias, Front Biosci., 2006, vol. 11, pp. 2554–2564.

    Article  PubMed  CAS  Google Scholar 

  15. Richter, C. and Kass, G.E.N., Oxidative Stress In Mitochondria: Its Relationship to Cellular Ca2+ Homeostasis, Cell Death, Proliferation, and Differentiation, Chem. Biol. Interaction, 1991, vol. 77, pp. 1–23.

    Article  CAS  Google Scholar 

  16. Fontaine, E. and Bernardi, P., Progress on the Mitochondrial Permeability Transition Pore: Regulation by Complex I and Ubiquinone Analogs, J. Bioenerg. Biomembr., 1999, vol. 31, pp. 335–345.

    Article  PubMed  CAS  Google Scholar 

  17. Steenbergen, C., Murphy, E., Watts, J.A., and London, R.E., Correlation between Cytosolic Free Cacium, Contracture ATP and Irreversible Ischemic Injury in Perfused Rat Heart, Circ. Res., 1990, vol. 66, pp. 135–146.

    PubMed  CAS  Google Scholar 

  18. Papa, S. and Skulachev, V.P., Reactive Oxygen Species, Mitochondria, Apoptosis and Aging, Mol. Cell Biochem., 1997, vol. 174, pp. 305–319.

    Article  PubMed  CAS  Google Scholar 

  19. Turrens, J.F., Mitochondrial Formation of Reactive Oxygen Species, J. Physiol., 2003, vol. 552, pp. 335–344.

    Article  PubMed  CAS  Google Scholar 

  20. Richter, C. and Frei, B., Ca2+ Release from Mitochondria Induced by Prooxidants, Free Radic. Biol. Med., 1988, vol. 4, pp. 365–375.

    Article  PubMed  CAS  Google Scholar 

  21. James, A.M., Smith, R.A.J., and Murphy, M.P., Antioxidant and Prooxidant Properties of Mitochondrial Coenzyme Q, Arch. Biochem. Biophys., 2004, vol. 423, pp. 47–56.

    Article  PubMed  CAS  Google Scholar 

  22. Fontaine, E., Ichas, F., and Bernardi, P., A Ubiquinone-Binding Site Regulates the Mitochondrial Permeability Transition Pore, J. Biol. Chem., 1998, vol. 273, no. 40, pp. 25734–25740.

    Article  PubMed  CAS  Google Scholar 

  23. Walter, L., Nogueira, V., Leverve, X., Heitz, M.-P., Bernardi, P., and Fontaine, E., Three Classes of Ubiquinone Analogs Regulate the Mitochondrial Permeability Transition Pore Through a Common Site J. Biol. Chem., 2000, vol. 275, pp. 29521–29527.

    Article  PubMed  CAS  Google Scholar 

  24. Abreu, R., Santos, D., and Moreno, A., Effects of Carvedilol and Its Analog BM-910228 on Mitochondrial Function and Oxidative Stress, J. Pharm. Exp. Therap., 2000, vol. 295, no. 3, pp. 1022–1030.

    CAS  Google Scholar 

  25. Okovity, S.V. and Smirnov, A.V., Antihypoxants, Eksperim. Klinich. Farmakol. (Rus.), 2001, vol. 64, no. 3, pp. 76–80.

    Google Scholar 

  26. Smirnov, V.S. and Kuz’mich, M.K., Hypoksen (Hypoxen), St. Petersburg—Moscow, FARMindex, 2001.

    Google Scholar 

  27. Uminky, A.A., Havsteen, B.H., and Bakaneva, V.F., Biokhimia flavonoidov i ikh znachenie v meditsine (Biochemistry and Medical Significance of Flavonoids), Pushchino, Photon-vek Company, 2007.

    Google Scholar 

  28. Vladimirov, Yu.A. and Archakov, A.I., Perekisnoe okislenie lipidov v biologicheskikh membranakh (Lipid Peroxidation in Biological Membranes), Moscow, Nauka, 1972.

    Google Scholar 

  29. Sassa, H., Takaisi, Y., and Terada, H., The Triterpene Celastrol as a Very Potent Inhibitor of Lipid Peroxidation in Mitochondria, Biochem. Biophys. Res. Commun., 1990, vol. 172, pp. 890–897.

    Article  PubMed  CAS  Google Scholar 

  30. Eaton, J.W. and Qian, M., Molecular Bases of Cellular Iron Toxicity, Free Rad. Biol. Med., 2002, vol. 32, no. 9, pp. 833–840.

    Article  PubMed  CAS  Google Scholar 

  31. Bodrova, M.E., Dedukhova, V.I., and Mokhova, E.N., Generation of Transmembrane Electrical Potential during NADH Oxidation via the External Pathway and the Fatty Acid Uncoupling Effect after Transient Opening of the Ca2+-Dependent Cyclosporin A-Sensitive Pore in Liver Mitochondria, Biokhimia, (Rus.), 2000, vol. 65, no. 4, pp. 562–569 [Transl. version in Biochemistry (Moscow), 2000, vol. 65, no. 4, pp 477–484].

    Google Scholar 

  32. Praktikum po biokhimii (Handbook on Biochemistry), Meschkova, N.P. and Severin, S.E., Eds., Moscow, Moscow University Publishing House, 1979, pp. 90–91.

    Google Scholar 

  33. Kuznetsova, I.N. and Maevsky, E.I., Emulsion of Perfluorocompound for Medical Use and Method for Its Production, Russian Patent no. 2259819, Bull. 25 (10.09.2005).

  34. Budnikov, E.Iu., Postnov, A.Iu., Afanas’eva, G.V., Doroshchuk, A.D., Bus’ko, E.V., and Postnov, Iu.V., Calcium Induced Calcium Release from Liver Mitochondria of Spontaneously Hypertensive Rats, Kardiologiia (Rus.), 2005, vol. 45, no. 7, pp. 49–53.

    Google Scholar 

  35. Zaitsev, V.G., Ostrovskii, O.V., and Zakrevskii, V.I., Correlation between Chemical Structure and a Target as Basis for Classification of Direct-Acting Antioxidants, Eksp. Klin. Farmakol., (Rus.), 2003, vol. 66, no. 4, pp. 66–70.

    CAS  Google Scholar 

  36. Huang, X., Zhai, D., and Huang, Y., Study on the Relationship between Calcium-Induced Calcium Release from Mitochondria and PTP Opening, Mol. Cell Biochem., 2000, vol. 213, pp. 29–35.

    Article  PubMed  CAS  Google Scholar 

  37. Grishina, E.V., Katuzan, Y.V., Popov, V.G., Kuz’mich, M.K., and Maevskii, E.I., About the Possible Mechanism of Antihypoxic Action of Hypoxen, Horizons of Biophysics, Ivanitskii, G.R., Ed., Pushchino, 2003, pp. 120–123.

  38. Grishina, E.V., Khaustova, Y.V., Pogorelova, V.G., Pogorelov, A.G., Kuz’mich, M.K., and Maevskii, E.I., Accelerated Utilization of Lactate under the Effect of Hypoxen after Intensive Exercise, Bull. Exp. Biol. Med. (Rus.), 2008, vol. 145, pp. 158–161 [Transl. version in Bull. Exp. Biol. Med., 2008, vol. 145, no. 2, pp. 198–201.]

    Article  CAS  Google Scholar 

  39. Radi, R., Turrens, J.F., and Freeman, B.A., Cytochrome C-Catalyzed Membrane Lipid Peroxidation by Hydrogen Peroxide, Arch. Biochem. Biophys., 1991, vol. 288, no. 1, pp. 118–125.

    Article  PubMed  CAS  Google Scholar 

  40. Rhee, S.G., Kim, K.H., Chae, H.Z., Yim, M.B., Uchida, K., Netto, L.E., and Stadtman, E.R., Antioxidant Defense Mechanisms, a New Thiol-Specific Antioxidant Enzyme, Ann. NY Acad. Sci., 1994, vol. 738, pp. 86–92.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290, Russia

    E. V. Grishina, Y. V. Khaustova & E. I. Maevsky

Authors
  1. E. V. Grishina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. V. Khaustova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. I. Maevsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. V. Grishina.

Additional information

Original Russian Text © E.V. Grishina, Y.V. Khaustova, E.I. Maevsky, 2009, published in Biologicheskie Membrany, 2009, Vol. 26, No. 6, pp. 505–513.

The article was translated by the authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grishina, E.V., Khaustova, Y.V. & Maevsky, E.I. Inhibition of Ca-induced calcium release from mitochondria by antiischemic phenol-based antioxidants. Biochem. Moscow Suppl. Ser. A 3, 459–466 (2009). https://doi.org/10.1134/S199074780904014X

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S199074780904014X

Key words

Search

Navigation