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Biochemistry (Moscow)

, Volume 80, Issue 12, pp 1614–1621 | Cite as

Effect of SkQ1 on activity of the glutathione system and NADPH-generating enzymes in an experimental model of hyperglycemia

  • Ya. G. VoronkovaEmail author
  • T. N. Popova
  • A. A. Agarkov
  • R. A. Zinovkin
Article

Abstract

We studied the effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on the antioxidant activity of the glutathione system and NADPH-generating enzymes in liver and blood serum of rats with hyperglycemia induced by protamine sulfate. It was found that intraperitoneal injection of SkQ1 prevented both decrease in reduced glutathione level and increase in activity of glutathione system enzymes–glutathione peroxidase, glutathione reductase, and glutathione transferase. Activity of NADPH-generating enzymes–glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase–was also attenuated by SkQ1. Probably, in this model of hyperglycemia, decreased level of reactive oxygen species in mitochondria led to the decreased burden on the glutathione antioxidant system and NADPH-generating enzymes. Thus, SkQ1 appears to be a promising compound for the treatment and/or prevention of the adverse effects of hyperglycemia.

Keywords

hyperglycemia SkQ1 glutathione glutathione peroxidase glutathione reductase glutathione transferase 

Abbreviations

DM

diabetes mellitus

DM2

type 2 diabetes mellitus

G6PDH

glucose-6-phosphate dehydrogenase

GP

glutathione peroxidase

GR

glutathione reductase

GSH

reduced glutathione

GT

glutathione transferase

NADP-IDH

NADP-isocitrate dehydrogenase

SkQ1

10-(6'-plasto-quinonyl)decyltriphenylphosphonium

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References

  1. 1.
    Stumvoll, M., Goldstein, B. J., and Van Haeften, T. W. (2005. Type 2 diabetes: principles of pathogenesis and therapy, Lancet, 365, 1333–1346.CrossRefPubMedGoogle Scholar
  2. 2.
    Roglic, G., Unwin, N., Bennett, P. H., Mathers, C., Tuomilehto, J., Nag, S., Connolly, V., and King, H. (2005. The burden of mortality attributable to diabetes realistic estimates for the year 2000, Diabetes Care, 28, 2130–2135.CrossRefPubMedGoogle Scholar
  3. 3.
    Dedov, I. I., Balabolkin, M. I., and Klebanova, Ye. M. (2004. Current aspects of transplantation of pancreatic islets in diabetes, Sakhar. Diabet, 2, 34–41.Google Scholar
  4. 4.
    Osipov, A., Azizova, O., and Vladimirov, Yu. (1990. Reactive oxygen species and their role in the organism, Usp. Biol. Khim., 31, 180–208.Google Scholar
  5. 5.
    Vincent, A. M., Russell, J. W., Low, P., and Feldman, E. L. (2004. Oxidative stress in the pathogenesis of diabetic neuropathy, Endocrin. Rev., 25, 612–628.CrossRefGoogle Scholar
  6. 6.
    Popova, T. N., Pashkov, A. N., Semehikhina, A. V., Popov, S. S., and Pakhmanova, T. I. (2008) Free-Radical Processes in Biosystems: a Textbook [in Russian], Kirillitsa, Stary Oskol.Google Scholar
  7. 7.
    Balabolkin, M. I. (2002. The role of protein glycation, oxidative stress in pathogenesis of vascular complications in diabetes, Sakhar. Diabet, 4, 4–16.Google Scholar
  8. 8.
    Lu, S. C. (1999. Regulation of hepatic glutathione synthesis: current concepts and controversies, FASEB J., 13, 1169–1183.PubMedGoogle Scholar
  9. 9.
    Upton, J., Edens, F., and Ferket, P. (2009. The effects of dietary oxidized fat and selenium source on performance, glutathione peroxidase, and glutathione reductase activity in broiler chickens, J. Appl. Poultry Res., 18, 193–202.CrossRefGoogle Scholar
  10. 10.
    Mannervik, B. (1980) Thioltransferases, in Enzymatic Basis of Detoxication (Jacoby, W., ed.) Academic Press, New York, Vol. 2, pp. 229–244.Google Scholar
  11. 11.
    Habig, W. H., Pabst, M. J., and Jakoby, W. B. (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation, J. Biol. Chem., 249, 71307139.Google Scholar
  12. 12.
    Schrauwen, P., and Hesselink, M. K. (2004. Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes, Diabetes, 53, 1412–1417.CrossRefPubMedGoogle Scholar
  13. 13.
    Kelley, D. E., He, J., Menshikova, E. V., and Ritov, V. B. (2002. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes, Diabetes, 51, 2944–2950.CrossRefPubMedGoogle Scholar
  14. 14.
    Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., and Shulman, G. I. (2004. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes, N. Engl. J. Med., 350, 664–671.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Green, K., Brand, M. D., and Murphy, M. P. (2004. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes, Diabetes, 53, 110–118.CrossRefGoogle Scholar
  16. 16.
    Antonenko, Y. N., Roginsky, V., Pashkovskaya, A., Rokitskaya, T., Kotova, E., Zaspa, A., Chernyak, B., and Skulachev, V. (2008. Protective effects of mitochondriatargeted antioxidant SkQ in aqueous and lipid membrane environments, J. Membr. Biol., 222, 141–149.CrossRefPubMedGoogle Scholar
  17. 17.
    Antonenko, Y. N., Avetisyan, A. V., Bakeeva, L. E., Chernyak, B. V., Vhertkov, V. A., Domnina, L. V., Ivanova, O. Yu., Izyumov, D. S., Khailova, L. S., Klishin, S. S., Korshunova, G. A., Lyamzaev, K. G., Muntyan, M. S., Nepryakhina, O. K., Pushkovskaya, A. A., Pletyushkina, O. Yu., Pustovidko, A. V., Roginsky, V. A., Rokitskaya, T. I., Ruuge, E. K., Saprunova, V. B., Severina, I. I., Simonyan, R. A., Skulachev, I. V., Skulachev, M. V., Sumbatyan, N. V., Sviryaaaeva, I. V., Tashlitsky, V. N., Vassiliev, I. M., Wyssololh, M. Yu., Yaguzhinsky, L. S., Zamyatnin, A. A., Jr., and Skulachev, V. P. (2008. Mitochondria-targeted plastoquinone derivative as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies, Biochemistry (Moscow), 73, 1273–1287.CrossRefGoogle Scholar
  18. 18.
    Galkin, I. I., Pletjushkina, O. Y., Zinovkin, R. A., Zakharova, V. V., Birjukov, I. S., Chernyak, B. V., and Popova, E. N. (2014. Mitochondria-targeted antioxidants prevent TNFa-induced endothelial cell damage, Biochemistry (Moscow) 79, 124–130.Google Scholar
  19. 19.
    Plotnikov, E. Y., Morosanova, M. A., Pevzner, I. B., Zorova, L. D., Manskikh, V. N., Pulkova, N. V., Galkina, S. I., Skulachev, V. P., and Zorov, D. B. (2013. Protective effect of mitochondria-targeted antioxidants in an acute bacterial infection, Proc. Natl. Acad. Sci. USA, 110, 31003108.CrossRefGoogle Scholar
  20. 20.
    Skulachev, V. P. (2013. Cationic antioxidants as a powerful tool against mitochondrial oxidative stress, Biochem. Biophys. Res. Commun., 441, 275–279.CrossRefPubMedGoogle Scholar
  21. 21.
    Paglialunga, S., Van Bree, B., Bosma, M., Valdecantos, M. P., Amengual-Cladera, E., Jorgensen, J. A., Van Beurden, D., Den Hartog, G. J., Ouwens, D. M., Briede, J. J., Schrauwen, P., and Hoeks, J. (2012. Targeting of mitochondrial reactive oxygen species production does not avert lipid-induced insulin resistance in muscle tissue from mice, Diabetologia, 55, 2759–2768.CrossRefPubMedGoogle Scholar
  22. 22.
    Ulyanov, A. M., and Tarasov, Yu. A. (2000. Insular system in animals with chronic heparin shortage, Vopr. Med. Khim., 46, 149–154.Google Scholar
  23. 23.
    Buzlama, V. S. (1997) Manual to Study the Processes of Lipid Peroxidation and Systems of Antioxidant Protection in Animals [in Russian], VNIVIPFiT, Voronezh, p. 35.Google Scholar
  24. 24.
    Voronkova, Ya. G., Popova, T. N., Agarkov, A. A., and Skulachev, M. V. (2015. Effect of 10-(6'-plasto-quinonyl)decyltriphenylphosphonium (SkQ1) on oxidative status in rats with hyperglycemia induced by administration of protamine sulfate, Biochemistry (Moscow), 80, 16061613.Google Scholar
  25. 25.
    McLennan, S. V., Heffernan, S., Wright, L., Rae, C., Fisher, E., Yue, D. K., and Turtle, J. R. (1991. Changes in hepatic glutathione metabolism in diabetes, Diabetes, 40, 344–348.CrossRefPubMedGoogle Scholar
  26. 26.
    Menshikova, E. B., Lankin, V. Z., Zenkov, N. K., Bondar, I. A., Krugovykh, N. F., and Trufakin, V. A. (2006) Oxidative Stress. Prooxidants and Antioxidants [in Russian], Slovo, Moscow.Google Scholar
  27. 27.
    Fetisova, E. K., Avetisyan, A. V., Izyumov, D. S., Korotetskaya, M. V., Tashlitsky, V. N., Skulachev, V. P., and Chernyak, B. V. (2011. P-glycoprotein providing multidrug resistance, prevents the expression of anti-apoptotic effect of mitochondria-targeted antioxidant SkQR1, Tsitologiya, 53, 488–497.Google Scholar
  28. 28.
    Baynes, J. W., and Thorpe, S. R. (1999. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm, Diabetes, 48, 1–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Zhang, Z., Apse, K., Pang, J., and Stanton, R. C. (2000. High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells, J. Biol. Chem., 275, 40042–40047.CrossRefPubMedGoogle Scholar
  30. 30.
    Bulteau, A.-L., Verbeke, P., Petropoulos, I., Chaffotte, A.F., and Friguet, B. (2001. Proteasome inhibition in glyoxal-treated fibroblasts and resistance of glycated glucose-6phosphate dehydrogenase to 20S proteasome degradation in vitro, J. Biol. Chem., 276, 45662–45668.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  • Ya. G. Voronkova
    • 1
    Email author
  • T. N. Popova
    • 1
  • A. A. Agarkov
    • 1
  • R. A. Zinovkin
    • 2
  1. 1.Voronezh State UniversityVoronezhRussia
  2. 2.Lomonosov Moscow State UniversityBelozersky Institute of Physico-Chemical BiologyMoscowRussia

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