Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2007; 53(4): 35-42


Inhibition of mitochondrial permeability transition pore is one of the mechanisms ofcardioprotective effect of coenzyme Q10

V.F.Sagach, G.L.Vavilova, O.V.Rudyk, F.V.Dobrovolsky, T.V.Shimanskaya, O.S.Medvedev

    O.O.Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv.


Abstract

Protective properties of coenzyme Q10 (CоQ10) on the: (i) Langendorff isolated guinea pig heart’s function under ischemia and reperfusion (I/R) and on the isolated mitochondria (ii) the mitochondrial permeability transition pore (MPTP) opening under exposure to calcium as natural MPTP inductor and phenylarsine oxide as oxidant - were studied. Physiological characteristic of contractile function, myocardial oxygen consumption and mitochondrial factor release as index of MPTP opening were compared before and after ischemia of isolated heart in control animals and animals with preliminary administration of CоQ10 per os . It have been shown that I/R disturbances of heart function were decreased and oxygen metabolism was normalised in animals treated with CоQ10 in compare to non-treated control. It was accompanied with sub- stantial stabilization of mitochondrial membrane. Decreased I/R disturbances of isolated heart from CоQ10 -treated animals were correlated to amount of mitochondrial factor released to coronary flow. Moreover, preliminary incubation of mitochon- dria, isolated from rat heart, with CоQ10 (10-5 mol/l) substan- tially prevented calcium and phenylarsine–induced, cyclosporine A-sensitive mitochondrial swelling. This protec- tive effect was increased in experiments with deenergizing mitochondria. Results of physiological and biochemical study reveal that one of the mechanisms of CоQ10‘s cardioprotective effect could be direct inhibition of mitochondrial permeability tran- sition pore opening during ischemia and reperfusion of the heart.

References

  1. Костерин С.А., Браткова Н.Ф., Курский М.Д. Роль сарколеммы и митохондрий в обеспечении каль- циевого контроля расслабления миометрия // Биохимия. – 1985. – 50, №8. – С.1350–1361.
  2. Сагач В.Ф., Шиманська Т.В., Надточій С.М. Попередження постреперфузійних порушень функції серця та неефективного використання кисню за допомогою інгібіторів мітохондріальної пори // Фізіол. журн. – 2002. – 48, №6. – С. 3–9.
  3. Сагач В.Ф., Шиманська Т.В., Надточій С.М. Фактор, який вивільнюється під час реперфузії ішемізо- ваного серця, може бути маркером відкриття мітохондріальної пори // Там само. – 2003. – 49, №4. – С. 6–12.
  4. Basso E., Fante L., Fowlkes J. et al. Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D // J. Biol. Chem. – 2005. – 280, №19. – P.8558–1861.
  5. Bonakdar R. A., Guarneri E. Coenzyme Q10 //Amer. Fam. Physic. – 2005. – 72, № 6. – P. 1064–1070.
  6. Brookes P.S., Darley-Usmar V.M. Role of calcium and superoxide dismutase in sensitizing mitochondria to peroxynitrite-induced permeability transition // Amer. J. Physiol. Heart. Circulat. Physiol. – 2004. – 286, №1. – P.H39–H46.
  7. Crompton M., Andreeva L. On the involment of a mi- tochondrial pore in reperfusion injury // Bas. Res. Cardiol. – 1993. – 88. – P. 513–523
  8. Fontaine E., Ichas F., Bernardi P. A ubiquinone-binding site regulates the mitochondrial permeability transition pore // J. Biol. Chem. – 1998. – 273, №40. – P.25734–25740.
  9. 9. Hausenloy D., Wynne A., Duchen M., Yellon D. Tran- sient mitochondrial permeability transition pore open- ing mediates preconditioning-induces protection// Cir- culation. – 2004. – 109. – P.1714–1717.
  10. 10. Huser J., Rechenmacher C., Blatter L. Imaging the per- meability pore transition in isolated mitochondria / / Biophys. J. – 1998. – 74. – P.2129–2137.
  11. Ito H., Nakajima T., Takikawa R. et al. Coenzyme Q10 attenuates cyanideactivation of the ATP-sensitive K+ channel current in single cardiac myocytes of the guinea-pig //Naunyn Schmiedebergs Arch. Pharmacol. – 1991. – 344. – Р.133–136.
  12. Javadov S.A., Clarke S., Das M. et al. Ischemic pre- conditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart // J. Physiol. – 2003. – 1, 549 (Pt 2). – P. 513–524.
  13. Kowaltowski A.J., Castilho R.F. Ca2+ acting at the ex- ternal side of the inner mitochondrial membrane can stimulate mitochondrial permeability transition induced by phenylarsine oxide // Biochim. and Biophys. Acta. – 1997. – 1322, №2–3. – P.221–229.
  14. Kowaltowski A., Castilho R.F., Vercesi A.E. Mito- chondrial permeability transition and oxidative stress // FEBS Lett. – 2001. – 495. – P.12–15.
  15. Kroemer G., Galluzzi L., Brenner C. Mitochondrial membrane permeabilization in cell death// Physiol.Rev. – 2007. – 87. – P.99–163.
  16. Lenartowicz E., Bernardi P., Azzone G.F. Phenylarsine oxide induces the cyclosporin A-sensitive membrane permeability transition in rat liver mitochondria // J. Bioenerg. Biomembr. – 1991. –23, №4. – P.679–688.
  17. Lenaz G. Role of mitochondria in oxidative stress and ageing // Biochim. and Biophys. Acta – 1998. – 1366, №1–2. – P.53–67.
  18. Li G., Zou L.Y., Cao C.M., Yang E.S. Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid tox- icity and oxygen-glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore // Biofactors. – 2005. – 25, № 1–4. – P.97–107.
  19. 19. Nayler WG. The use of coenzyme Q10 to protect is- chemic heart muscle. – In: Biomedical and clinical as- pects of coenzyme Q. – Amsterdam: Elsevier. – 1980 – 2. – Р. 409–425.
  20. 20. Papucci L., Schiavone N., Witort E. et al. Coenzyme Q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scav- enging property // J. Biol. Chem. – 2003. – 278, № 30. – P.28220–28228.
  21. Ohharа H., Kanaide Н., Yoshimura R. et al. A protec- tive effect of coenzyme Q 10 on ischemia and reperfu- sion of the isolated perfused rat heart // J.Mol. Cell.Cardiol. – 1981. – 13, №1. – P.65–74.
  22. Sadek H.A., Nulton-Persson A.C., Szweda P.A., Szweda L.I. Cardiac ischemia/reperfusion, aging,and redox-dependent alterations in mitochondrial function // ABB. – 2003. – 420. – P.201–208.
  23. Sagach V., Scrosati M., Fielding J. et al. The water- soluble vitamin E analogue trolox protects against is- chaemia/reperfusion damage in vitro and ex vivo. A comparison with vitamin E // Pharmacol.Res. – 2002. – 45. – P.435–439.
  24. Shults C.W., Haas R.H., Passov D., Beal M.F. Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects // Ann. Neurol. – 1997. – 42, № 2. – P.261–264.
  25. Skulachev V. P. Programmed death phenomena: from organelle to organism // Ann. N.Y. Acad. Sci. – 2002. – 959. – P.214–237.
  26. Sugiyama S., Kitazawa M., Ozawa T. et al. Anti-oxi- dative effect of coenzyme Q10 // Experientia – 1980. – 36. – Р.1002–1003.
  27. Walter L., Miyoshi H., Leverve X. et al. Regulation of the mitochondrial permeability transition pore by ubiquinone analogs. A progress report // Free Radic. Res. – 2002. – 36, № 4. – P.405–412.
  28. Yamamura T., Otani H., Nakao Y. et al. Dual involve- ment of coenzyme Q10 in redox signaling and inhibition of death signaling in the rat heart mitochondria // Antioxid Redox Signal. – 2001. – 3, №1. – P.103–112.
  29. 29. Young A.J., Johnson S., Steffens D.C., Doraiswamy P.M. Coenzyme Q10: a review of its promise as a neuroprotectant // CNS Spectr. – 2007. – 12, № 1. – P.62–68.
  30. 30. Zorov D.B., Filburn C.R., Klotz L.O et al. Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochon- drial permeability transition in cardiac myocytes // J.Exp. Med. – 2000. – 192, №7. – P.1001–1014.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.