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Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS- and Age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke)

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Abstract

Effects of 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6′-plastoquinonyl) decylrhod-amine 19 (SkQR1) on rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125–250 nmol/kg per day for 2–3 weeks) was found to decrease the heart infarction region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals in 2–4 days, whereas one injection of SkQ1 or SkQR1 (1 μmol/kg a day before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion, a single intraperitoneal injection of SkQR1 to a rat (1 μmol/kg a day before operation) effectively decreased the damaged brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.

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Abbreviations

AI:

area of infarction

CK:

creatine kinase

DCF:

5-(-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate

ICF:

intensity of the (heart) contractile function

LDH:

lactate dehydrogenase

LV:

the heart left ventricle

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

RA:

risk area

ROS:

reactive oxygen species

SkQs:

cationic derivatives of plastoquinone or methyl plastoquinone

SkQ1:

10-(6′-plastoquinonyl) decyltriphenylphosphonium

SkQR1:

10-(6′-plastoquinonyl) decylrhodamine 19

TMRE:

tetramethylrhodamine ethyl ester

TTC:

2,3,5-triphenyltetrazolium chloride

References

  1. Antonenko, Y. N., Avetisyan, A. V., Bakeeva, L. E., Chernyak, B. V., Chertkov, 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., Pashkovskaya, A. A., Pletjushkina, 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., Sviryaeva, I. V., Tashlitsky, V. N., Vassiliev, J. M., Vyssokikh, M. Yu., Yaguzhinsky, L. S., Zamyatnin, A. A., Jr., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1273–1287.

    Article  CAS  Google Scholar 

  2. Pisarenko, O. I., Studneva, I. M., Serebriakova, L. I., Tskitishvili, O. V., and Timoshin, A. A. (2005) Kardiologiya, 45, 37–44.

    CAS  PubMed  Google Scholar 

  3. Watanabe, S., Hoffman, J. R., Craik, R. L., Hand, P. J., Croul, S. E., Reivich, M., and Greenberg, J. H. (2001) Stroke, 32, 2615–2623.

    Article  CAS  PubMed  Google Scholar 

  4. Kundrotiene, J., Wagner, A., and Liljequist, S. (2002) J. Neurotrauma, 19, 69–84.

    Article  PubMed  Google Scholar 

  5. Andersson, B., Bjelke, B., and Sykova, E. (2006) Physiol. Res., 55, 339–348.

    CAS  PubMed  Google Scholar 

  6. Andersson, D., Wu, X., Bjelke, D., and Sekova, E. (2004) J. Neurosci. Res., 77, 901–912.

    Article  CAS  PubMed  Google Scholar 

  7. Andrews, R., and Muto, R. (1992) Neurol. Res., 14, 12–18.

    CAS  PubMed  Google Scholar 

  8. Skulachev, V. P., Bakeeva, L. E., Chernyak, B. V., Domnina, L. V., Minin, A. A., Pletjushkina, O. Y., Saprunova, V. B., Skulachev, I. V., Tsyplenkova, V. G., Vasiliev, J. M., Yaguzhinsky, L. S., and Zorov, D. B. (2004) Mol. Cell. Biochem., 256/257, 341–358.

    Article  CAS  Google Scholar 

  9. Plotnikov, E. Y., Kazachenko, A. V., Vyssokikh, M. Y., Vasileva, A. K., Tcvirkun, D. V., Isaev, N. K., Kirpatovsky, V. I., and Zorov, D. B. (2007) Kidney Int., 72, 1493–1502.

    Article  CAS  PubMed  Google Scholar 

  10. Serviddio, G., Romano, A. D., Gesualdo, L., Tamborra, R., Di Palma, A. M., Rollo, T., Altomare, E., and Vendemiale, G. (2008) Nephrol. Dial. Transplant., 23, 1504–1512.

    Article  PubMed  Google Scholar 

  11. McCord, J. M. (1985) N. Engl. J. Med., 312, 159–163.

    CAS  PubMed  Google Scholar 

  12. Baud, L., and Ardaillou, R. (1993) Br. Med. Bull., 49, 621–629.

    CAS  PubMed  Google Scholar 

  13. Moro, M. A., Almeida, A., Bolanos, J. P., and Lizasoain, I. (2005) Free Rad. Biol. Med., 39, 1291–1304.

    Article  CAS  PubMed  Google Scholar 

  14. Webster, K. A. (2007) Trends Pharmacol. Sci., 28, 492–499.

    Article  CAS  PubMed  Google Scholar 

  15. Goldhaber, J. I., and Liu, E. (1994) J. Physiol., 477, 135–147.

    CAS  PubMed  Google Scholar 

  16. Okabe, E., Tsujimoto, Y., and Kobayashi, Y. (2000) Antioxid. Redox. Signal, 2, 47–54.

    Article  CAS  PubMed  Google Scholar 

  17. Meissner, A., and Morgan, J. P. (1995) Am. J. Physiol., 268, 100–111.

    Google Scholar 

  18. Kojima, S., Wikman-Coffelt, J., Wu, S. T., and Parmley, W. W. (1994) Am. J. Physiol., 266, 1473–1484.

    Google Scholar 

  19. Camello-Almaraz, M. C., Pozo, M. J., Murphy, M. P., and Camello, P. J. (2006) J. Cell Physiol., 206, 487–494.

    Article  CAS  PubMed  Google Scholar 

  20. Adlam, V. J., Harrison, J. C., Porteous, C. M., James, A. M., Smith, R. A. J., Murphy, M. P., and Sammut, I. A. (2005) FASEB J., 19, 1088–1095.

    Article  CAS  PubMed  Google Scholar 

  21. Taggart, D. P., Jenkins, M., Hooper, J., Hadjinikolas, L., Kemp, M., Hue, D., and Bennett, G. (1996) Ann. Thorac. Surg., 61, 829–833.

    Article  CAS  PubMed  Google Scholar 

  22. Kalenikova, E. I., Gorodetskaya, E. A., Kolokolchikova, E. G., Shashurin, D. A., and Medvedev, O. S. (2007) Biochemistry (Moscow), 72, 332–338.

  23. Verma, D. D., Hartner, W., Levchenko, T., and Torchilin, V. (2007) J. Mol. Cell. Cardiol., 42, 214–215.

    Article  Google Scholar 

  24. Rokitskaya, T. I., Klishin, S. S., Severina, I. I., Fedorov, I. I., Tashlitsky, V. N., Antonenko, Y. N., and Skulachev, V. P. (2008) J. Membr. Biol., 222, 141–149.

    Article  PubMed  Google Scholar 

  25. Neroev, V. V., Archipova, M. M., Bakeeva, L. E., Fursova, A. Zh., Grigorian, E. N., Grishanova, A. Yu., Iomdina, E. N., Ivashchenko, Zh. N., Katargina, L. A., Khoroshilova-Maslova, I. P., Kilina, O. V., Kolosova, N. G., Kopenkin, E. P., Korshunov, S. S., Kovaleva, N. A., Novikova, Yu. P., Philippov, P. P., Pilipenko, D. I., Robustova, O. V., Saprunova, V. B., Senin, I. I., Skulachev, M. V., Sotnikova, L. F., Stefanova, N. A., Tikhomirova, N. K., Tsapenko, I. B., Shchipanova, A. I., Zinovkin, R. A., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1317–1328.

    Article  CAS  Google Scholar 

  26. Anisimov, V. N., Bakeeva, L. E., Egormin, P. A., Filenko, O. F., Isakova, E. F., Manskikh, V. N., Mikhelson, V. M., Panteleeva, A. A., Pasyukova, E. G., Pilipenko, D. I., Piskunova, T. S., Popovich, I. G., Roshchina, N. V., Rybina, O. Yu., Samoylova, T. A., Saprunova, V. B., Semenchenko, A. V., Skulachev, M. V., Spivak, I. M., Tsybul’ko, E. A., Tyndyk, M. L., Vyssokikh, M. Yu., Yurova, M. N., Zabezhinsky, M. A., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1329–1342.

    Article  CAS  Google Scholar 

  27. Skulachev, V. P. (2007) Biochemistry (Moscow), 72, 1385–1396.

  28. Agapova, L. S., Chernyak, B. V., Domnina, L. V., Dugina, V. B., Efimenko, A. Yu., Fetisova, E. K., Ivanova, O. Yu., Kalinina, N. I., Khromova, N. V., Kopnin, B. P., Kopnin, P. B., Korotetskaya, M. V., Lichinitser, M. R., Lukashov, A. L., Pletjushkina, O. Yu., Popova, E. N., Skulachev, M. V., Shagieva, G. S., Stepanova, E. V., Titova, E. V., Tkachuk, V. A., Vasiliev, Y. M., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1300–1316.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    L. E. Bakeeva, N. K. Isaev, E. Y. Plotnikov, V. B. Saprunova, A. K. Vasilyeva, D. B. Zorov & V. P. Skulachev

  2. Department of Brain Research, Institute of Neurology, Russian Academy of Medical Sciences, Pereulok Obukha 5, 105064, Moscow, Russia

    I. V. Barskov, N. K. Isaev, S. B. Levina & E. V. Stelmashook

  3. Center for Mitoengineering, Lomonosov Moscow State University, 119991, Moscow, Russia

    M. V. Egorov, S. V. Kozlovsky, M. V. Skulachev & V. P. Skulachev

  4. Institute of Experimental Cardiology, Cardiology Research Center, 3-ya Cherepkovskaya ul. 15A, 121552, Moscow, Russia

    V. I. Kapelko, V. L. Lakomkin, O. I. Pisarenko, L. I. Serebryakova, I. M. Studneva & O. V. Tskitishvili

  5. Institute of Urology, 3-ya Parkovaya ul. 51, 105425, Moscow, Russia

    A. V. Kazachenko & V. I. Kirpatovsky

  6. Serbsky State Research Center of Social and Forensic Psychiatry, Kropotkinsky Pereulok 23, 119992, Moscow, Russia

    I. V. Victorov

  7. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991, Moscow, Russia

    V. P. Skulachev

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  1. L. E. Bakeeva
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  2. I. V. Barskov
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  6. A. V. Kazachenko
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  7. V. I. Kirpatovsky
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  8. S. V. Kozlovsky
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  11. O. I. Pisarenko
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  12. E. Y. Plotnikov
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  13. V. B. Saprunova
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  14. L. I. Serebryakova
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  15. M. V. Skulachev
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  16. E. V. Stelmashook
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  17. I. M. Studneva
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  18. O. V. Tskitishvili
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  19. A. K. Vasilyeva
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  20. I. V. Victorov
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  21. D. B. Zorov
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  22. V. P. Skulachev
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Corresponding author

Correspondence to V. P. Skulachev.

Additional information

Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1607–1621.

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Bakeeva, L.E., Barskov, I.V., Egorov, M.V. et al. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS- and Age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke). Biochemistry Moscow 73, 1288–1299 (2008). https://doi.org/10.1134/S000629790812002X

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  • DOI: https://doi.org/10.1134/S000629790812002X

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