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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

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. 2010; 56(4): 76-85

The role of mitochondria in theno-dependent regulation of na[sup]+[/sup], k[sup]+[/sup]-atpase activity in rat aorta

O.V. Akopova, A.V. Kotsiuruba,O.N. Kharlamova, Yu.P. Korkach, V.F. Sagach

    O.O. Bogomoletz Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv;A.V. Palladin Institute of Biochemistry, National Academy ofSciences of Ukraine, Kyiv


In experiments in vivo we studied the interaction between two ion-transporting mechanisms of cardiovascular system -Na+,K+-ATPase of rat aorta and Ca2+-uptake system of mito­chondria in short-term response to different doses of NO do­nor, nitroglycerine (NG). The activity of the Na+,K+-ATPase was determined in rat aorta, and mitochondrial uptake of Ca2+ was studied in rat heart mitochondria assuming that metabo­lism induced by NO in cardiac mitochondria is similar to that in rat aortic mitochondria. The data show a coordinated dose-dependent action of NG on Na+,K+-ATPase activity as well as Ca2+-uptake in mitochondria. An activation of Na+,K+-AT-Pase by low dose of NG (0,25 mg/kg body weight) is accom­panied by the activation of Ca2+-uptake in mitochondria as a result of inhibition of permeability transition pore. However, further increase of the dose of the drug leads to reciprocal changes of studied parameters: the decrease in Na+-pump ac­tivity below the control level and the increase of Ca2+-uptake in mitochondria with a peak at 1,0 mg/kg NG, which takes place in parallel with the dramatic rise in the level of ROS and RNS together with their toxic products, nitrosothiols (NT) and free iron (Fe2+) content in mitochondria. Strong correlation between Ca2+-uptake and Fe2+-release, Fe2+-release and .OH-radical formation, the rise in .OH-radical level and the decrease of that of H2O2 and mitochondrial NT together with the inhi­bition of Na+,K+-ATPase favor a hypothesis that oxidative stress in rat aorta is of mitochondrial origin due to an enhanced uptake of Ca2+ into mitochondrial matrix, Fe2+ deliverance and manifold increase in .OH-radical formation from decomposi-tion of hydroperoxide in Haber-Weiss reaction and the decom­position of mitochondrial NT via formation of peroxynitrite, both catalysed by Fe2+, with subsequent release of OH-radi-cal. Effective abolition of Na+,K+-ATPase inhibition by po­tent antioxidant melatonine gives the evidence of the oxidative nature of Na+,K+-ATPase inhibition by nitric oxide in rat aorta.


  1. Акопова О.В., Коцюруба А.В., Ткаченко Ю.П., Сагач В.Ф. Оксид азоту пригнічує відкриття мітохонд-ріальної пори і збільшує кальцієву ємність мітохондрій in vivo //Фізіол.журн. - 2005. - 51, №3. -С. 3-11.
  2. Акопова О.В., Харламова О.М., Коцюруба А.В., Ко+кач Ю.П., Сагач В.Ф. Вплив оксиду азоту на Na , K+-АТФазу в тканині аорти щурів // Там само. - 2009. - 55, №1. -С.27-35.
  3. Акопова О.В. Роль митохондриальной поры в трансмембранном обмене кальция в митохондриях / /Укр.біохім. журн. - 2008. - 80, №3. - С.40-47.
  4. Болдырев А.А. Na+, K+-АТРаза как олигомерный ансамбль //Биохимия. - 2001. - 66. - С.1013-1025.
  5. Ванин А.Ф. Динитрозильные комплексы железа и S-нитрозотиолы - две возможные формы стаби­лизации и транспорта оксида азота в биологических системах // Биохимия, 1998. - 63, №7. - С.924-938.
  6. Коркач Ю.П., Дудченко Н.О., Коцюруба А.В., Присяжна О.Д., Сагач В.Ф.. Роль негемового заліза у протекторній дії екдистерону на розвиток стрептозотоцин-індукованої гіпоглікемії у щурів // Укр.біохім. журн. - 2008. - 80, №1. - С.46-51.
  7. Костюк П.Г., Костюк О.П., Лук’янець О.А. Іони кальцію у функції мозку - від фізіології до патології. - К.: Наук. думка. - 2005. - 198 с
  8. Скулачев В.П. Энергетика биологических мембран. -М.: Наука, 1989. - 564 с
  9. 9. Acuna-Castroviejo D., Martin M., Macias M., Escames G., Leon J., Khaldy H., Reiter R.J. Melatonin, mito­chondria, and cellular bioenergetics //J. Pineal Res. -2001. - 30. - P.65-74.
  10. 10. Basaga H.S. Biochemcal aspects of free radicals //Cell Biol. - 1990. - 68,№5. - P.989-998.
  11. Blaustein M.P. Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness // Amer. J. Physiol. - 1993. - 264. - P. C1367-C1387.
  12. Brown G.C. Nitric oxide and mitochondrial respiration //Biochim. Biophys. Acta. 1999. - 1411. - P.351-369.
  13. Conte D., Narindrasorosa K.S., Sarcar B. In vivo and in vitro iron-replaced zinc finger generated free radicals and caused DNA damage // J. Biol. Chem. - 1996. -271,№9. - P.5125-5130.
  14. Daiber A., Wenzel P., Oelze M., Schuhmacher S., Jansen T., Munzel T. Mitochondrial aldehyde dehydrogenase (ALDH-2) - maker of and marker for nitrate tolerance in response to nitroglycerine treatment // Chem. Biol. Interact. - 2009. - 178, №1-3. - P. 40-47.
  15. Frieden M., James D., Castelbou C. Danckaert A.., Martinon J.-C, Demareux N. Calcium homeostasis during mitochondrial fragmentation and perinuclear clustering induced by hFis1 // J. Biol. Chem. - 2004. -279. - P.22704-22714.
  16. Green L.C., David A.W., Glogovski J. Analysis of ni­trate, nitrite and [15N]nitrate in biological fluids // Anal. Biochem. - 1982. - 126, №1. - P.131-138.
  17. Huwiler M., Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase/HO/iodide system // Eur. J. Biochem., 1984. - 141, №1. - P. 69-74.
  18. Ignarro L.J., Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide // Circulat. Res. - 2002. - 90, №1. - P.21-28.
  19. 19. Lander H.M. An essential role for free radicals and derived species in signal transduction // FASEB J. -1997. - 11. - P.118-124.
  20. 20. Patchornik G., Goldshleger R., Karlish S.J.D. The complex ATP-Fe2+ serves as a specific affinity cleavage reagent in ATP-Mg+ sites of Na, K-ATPase: altered ligation of Fe2+(Mg2+) ions accompanies the E1P^E P conformational change //Proc. Natl. Acad. Sci. USA. -2000. - 97, №22. - P.1 1954-11959.
  21. Pfeiffer S., Gorren A.C.F., Schmidt K., Wermer E.R., Hansert B., Bohle D.S., Mayer B. Metabolic fate of peroxynitrite in aqueous solution. Reaction with nitric oxide and pH-dependent decomposition to nitrite and oxygen in 2:1 stoichiometry// J. Biol. Chem. - 1997. -272, №6. - P.3465-3470.
  22. Rizzuto R., Bernardi P., Pozzan T. Mitochondria as all-round players of the calcium game // J. Physiol., 2000. - 529, №1. - P. 37-47.
  23. Rizzuto R., Pinton P., Carrington W., Fay F.S., Fogarty K.E., Lifshitz L.M., Tuft R.A., Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mi­tochondrial Ca2+ responses // Science. - 1998. - 280. -P.1763-1766.
  24. Rossi C.S., Bielawsky J., Lehninger A.L. Separation of H+ and OH- in the extramitochondrial and mitochon­drial phases during Ca2+-activated electron transport / / J. Biol. Chem. - 1966. - 241, №8. - P.1919-1921.

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