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. 2006; 52(3): 25-33


S.N Pyvovar, V.I. Korzhov., R.B Strutinskii, L.M. Yagupolskii, A.A. Moibenko

S.N Pyvovar, V.I. Korzhov., R.B Strutinskii, L.M. Yagupolskii, A.A. Moibenko

    O. O. Bogomolets Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv


Abstract

The cardioprotective mechanism of KATP channel openers and especially their influence on mitochondrial respiration has not been clarified yet. In this article we investigated the effect of DiazoFm and DiazoFp, the new fluor- containing analogues of diazoxide and the potential mitochondrial KATP channel openers, on the oxidative phosphorylation in the isolated mitochondria. It was shown that the influence of KATP channel openers on ADP- stimulated oxygen consumption (State 3) depended on the substrates we used (succinate or 2-oxoglutarate sodium). We С.М. Пивовар, В.І. Коржов, Р.Б. Струтинський, Л.М. Ягупольський, О.О. Мойбенко 23ISSN 0201-8489 Фізіол. журн., 2006, Т. 52, № 3 have shown that the depression of State 3 was less when we used DiazoFm (30 мM) and DiazoFp (30 мM) in comparison with Diazoxide in experiments where succinate was used. The fluor-containing KATP channels openers did not significantly change the activity of succinate dehydrogenase in comparison with diazoxide (it decreased succinate dehydrogenase activity by 27%). Thus, the fluor-containing analogues of diazoxide did not significant influence on the complex II of the respiratory chain. In the other experiments when we used 2-oxoglutarate sodium as an oxidative substrate, DiazoFp increased ADP- stimulated oxygen consumption by 33%. All the studied KATP openers have an uncoupling effect, regardless the substrates we used. This effect was more significant when we used succinate as a substrate. We have shown that the uncoupling effect of oxidative phosphorylation is a consequence of KATP channels activation. This statement was proved by 5-hydroxydecanoate (200 мM) with depressed influence of Diazoxide and its fluoring-containing analogues. Conclusion. The fluor-containig KATP channels openers had not direct influence on the respiratory chain in mitochondria, but activation mitochondrial KATP channels by them lead to uncoupling phosporylation and respiration

References

  1. Єщенко Н.Д., Вольский Г.Г. Определение количества янтарной кислоты и активности сукцинатдегид- рогеназы. – В кн.: Методы биохимических исследо-ваний – Л.: Изд-во Ленинград. ун-та. – 1982. –С. 207–212.
  2. Кудзина K.Ю., Евтодиенко Ю.В. Реконструкция К+- транспортирующей системы митохондрий на искусственных фосфолипидных мембранах // Биофизика. – 1974. – 19, №5. – С. 765–766.
  3. Лукьянова Л.Д. Роль биоэнергетических нарушений в патогенезе гипоксии // Патол. физиология. и эксперим. терапия. – 2004. – №2. – С. 2–11.
  4. Нагібін В.С., Досенко В.Є., Пивовар С.М. та ін. Фторований аналог діазоксиду попереджає апоптоз неонатальних кардіоміоцитів під час аноксії-реоксигенації // Фізіол. журн. – 2004. – 50, №3. – С. 3–8.
  5. Пивовар С.М., Струтинський Р.Б., Ягупольський Л.М., Мойбенко О.О. Дослідження механізму дії нових торвмісних аналогів діазоксиду на судинний тонус // Там само. – № 2. – С. 27–33.
  6. Практикум по биохимии / Под ред. С.Е. Северина и .А. Соловьевой. – М.: Изд-во Москов. ун-та, 1989. – C. 480–483.
  7. Ткаченко Н.М., Мойбенко О.О., Кургалюк Н.М. Вплив модуляторів АТФ-чутливих калієвих каналів і інтервальної гіпоксії на мітохондріальне дихання при стресі // Укр. біохім. журн. – 2003. – 75, №6. –С. 15–22.
  8. Ткаченко Г.М., Кургалюк Н.М., Кордунська О.Є. оль діазоксиду в процесах мітохондріального енергозабезпечення печінки залежно від індиві- дуальної фізіологічної резистентності у шурів //Клін. та експерим. патологія. – 2004. – 3, № 2. –С. 468–470.
  9. 9. Cancherini D.V., Trabuco L.G., Reboucas N.A., Kowaltowski A.J. ATP-sensitive K+ channels in renal mitochondria // Amer. J. Physiol. Renal. Physiol. – 2003. – 285, №6 – P. 1291–1296.10. Сhance B., Williams G.R. The respiratory chain andoxidative phosphorylation // Adv. Enzymol. – 1956. –17. – P. 65–134.
  10. Crestanello J.A., Doliba N.M., Babsky A.M. et al. Opening of potassium channels protects mitochondrial function from calcium overload // J. Surg. Res. – 2000. – 94. – Р. 116–123
  11. Dzeja P.P., Bast P., Ozcan C. et al. Targeting nucleotide- requiring enzymes: implications for diazoxide-induced cardioprotection // Amer. J. Physiol. Heart Circulat. Physiol. – 2003. – 284. – P. 1048–1056.
  12. Eells J.T., Henry M.M., Gross G.J., Baker J.E. Increased mitochondrial KATP channel activity during chronic myocardial hypoxia is cardioprotection mediated by improved bioenergetics? // Circulat. Res. –2000. – 87. – P. 915–921.
  13. Fernandes M.A, Santos M.S., Moreno A.J. et al. Glibenclamide interferes with mitochondrial bioener- getics by inducing changes on membrane ion permeability // J. Biochem. Mol. Toxicol. – 2004. – 18, №3. – Р. 162–169.
  14. Garlid K.D., Paucek P., Yarov-Yarovoy V. et al. Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels: possible mecanism of cardioprotection // Circulat. Res. – 1997. – 81. – P. 1072–1072.
  15. Grimmsmann T. Rustenbeck I. Direct effects of diazoxide on mitochondria in pancreatic B-cells and on isolated liver mitochondria // Brit. J. Pharmacol. – 1998. – 123. – P. 781–788.
  16. Hanley P.J., Mickel M., Loffler M. et al. KATP channel-independents targets of diazoxide and 5- hydroxydecanoate in the heart //J.Physiol. – 2002. – 542, №.3. – P. 735–741.
  17. Hanley P.J., Drose S., Brandt U. et al. 5-Hydroxy- decanoate is metabolised in mitochondria and creates a rate-limiting bottleneck for {beta}-oxidation of fattyacids // J. Physiol. – 2004. – 562, Pt 2. – Р. 307–318.
  18. 19. Holmuhamedov E.L., Jahangir A. Potassium channel openers are uncoupling protonophores: implication in cardioprotection // FEBS Lett. – 2004. – 568, № 1–3. – Р. 167–170.
  19. 20. Holmuhamedov E.L., Jovanovic S., Dzeja P.P. et al. Mitochondrial ATP-sensirive K+ channels modulate cardiac mitochondrial function // Amer. J. Physiol. Heart Circulat. Physiol. – 1998. – 275. – P. 1567–1576.
  20. Jaburek M., Yarov-Yarovoy V., Paucek P., Garlid K.D. State-dependent inhibition of the mitochondrial KATP Вплив фторвмісних активаторів
  21. ISSN 0201-8489 Фізіол. журн., 2006, Т. 52, № 3 33 channel by glyburide and 5-hydroxydecanoate // J. Biol.Chem. – 1998. – 273, № 22. – P. 13578–13582.
  22. Lowry O.H., Rosenbrough N., Farr A.L., Randall R.I. Protein measurement with the Folin phenol reagent //Ibid. – 1951. – 193, № 1. – P. 265–275.
  23. Lembert N., Idahl L-A., Ammon H.P.T. K-ATP channel independent effects of pinacidil on ATP production in isolated cardiomyocyte or pancreatic ?-cell mitochondria // Biochem. Pharmacol. – 2003. – 65. –P. 1835–1841.
  24. Lim K.H.H., Javadov S.A., Das M. et al. The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration //J. Physiol. – 2002. – 545, №. 3. –P. 961–974.
  25. Mamon S., Roucou X., Rigoulet M., Guerin M. Stimulation of oxidative phosphorylation by electro- phoretic K+ entry associated to electroneutral K+/H+ exchange in yeast mitochondria // Biochim. et Biophys.Acta. – 1995. – 1231. – P. 282–288.
  26. Minners J., McLeod C.J., Sack M.N. Mitochondrial plasticity in classical ischemic preconditioning-moving beyond the mitochondrial KATP channel // Cardiovasc. Res. – 2003. – 59, №1. – Р. 1–6.
  27. O’Rourke B. Evidence for mitochondrial K+ channels and their role in cardioprotection //Circulat. Res. – 2004. – 94. – P.420–432.
  28. Paucek P., Mironovae G., Mahdi F. et al. Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K+ channel from rat liver and beef heart mitochondria // J. Biol. Chem. – 1992 – 267, № 36. –Р. 26062–26069.
  29. 29. Schafer G., Wegener C., Portenhauser R., Bojanovski D. Diazoxide, an inhibitor of succinate oxidation // Biochem. Pharmacol. – 1969. – 18. – P. 2678–2681.
  30. 30. Tritto I., D’Andrea D., Eramo N. et al. Oxygen radicals can induce preconditioning in rabbit hearts // Circulat. Res. – 1997. – 80. – P. 743–748.

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