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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. 2012; 58(2): 3-15


Reactive nitrogenand oxygen species metabolism in rat heart mitochondria upon administration of no donorin vivo

O.V. Akopova, Yu.P. Korkach, A.V. Kotsuruba, L.I. Kolchinskaya, V.F. Sagach

    O.O. Bogomoletz Institute of Physiology Ukrainian NationalAcademy of Science, Kyiv.


Abstract

Some aspects of reactive nitrogen and oxygen species (RNS and ROS) metabolism in rat heart mitochondria under admin­istration of different doses of nitroglycerine (NG) in vivo are discussed. It is shown that NG administration results in a dose-dependent increase in Ca2+-uptake in mitochondria, due to the dose-dependent inhibition of mitochondrial permeabil­ity transition pore (MPTP) in vivo and the activation of Ca2+-dependent mitochondrial NOS. It was shown that NOS activ­ity increases in accord with the increase of Ca2+-uptake in mitochondria. The dose-dependent activation of nitrat-reductase is observed. However, nitrite production decreases dose-dependently, according to the change of NO2-/NO3- ratio on behalf of NO3-, the end product of NO transformations. The relation between nitrosylation of mitochondrial proteins with the nitrosothiols formation and nitrate production also changes towards NO3-, which shows the activation of oxida­tion reactions in heart mitochondria after NG administration. Accordingly, dose-dependent increase in lipid peroxidation (LP) products is shown, the hallmark of the membrane damage in mitochondria. It is established that the cause of oxidative stress, besides the dose-dependent increase in ROS produc­tion (hydroperoxide, superoxide and hydroxyl-radical), lies in the increase of free iron content, derived from the oxidation of mitochondrial iron-containing proteins. The iron interaction with hydroperoxide following Fenton reaction as well as free-radical decomposition of peroxynitrite, derived from NO3- are the possible cause of manifold increase in ROS as well as LP production, and RNS oxidation to NO3-. Thus, NO-dependent MPTP blockage, due to NO synthesis in mitochondria in vivo, results in the activation of both constituents of NO-cycle: NOS-dependent, due to Ca2+-dependent activation of mito-chondrial NOS, and nitrate-reductase-dependent, due to the increase in NO3- formation. However, increase in ROS pro­duction, augmented by the iron release, leads to the oxidative stress and the shift of RNS metabolism towards NO3- forma­tion, in spite of the activation of nitrate-reductase-dependent pathway of NO-cycle. It is shown that reversible MPTP open­ing in vitro diminishes ROS production, whereas MPTP block­age by cyclosporine A restores the ROS formation to control level. Thus, MPTP-dependent inhibition of ROS overproduc­tion both in vitro and in vivo, shows the importance of MPTP in the regulation of ROS and RNS metabolism in mitochon­dria.

Keywords: reactive nitrogen and oxygen species, nitroglycer-ine, calcium, mitochondrial permeability transition pore, heartmitochondria.

References

  1. Акопова О.В., Сагач В.Ф. Высвобождение кальция из митохондрий печени крыс в условиях коллапса мембранного потенциала // Укр. біохім. журн. - 2005. -77, №3. -С. 68-75.
  2. Акопова О.В., Харламова О.М., Коцюруба А.В., Коркач Ю.П., Сагач В.Ф. Вплив оксиду азоту на Na+,K+-АТФазу в тканині аорти щурів //Фізіол. журн. - 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. Аликулов З.Л., Львов Н.П., Кретович В.Л. Нитрат-и нитритредуктазная активность молока // Биохимия. -1980. - 45, №9. -С. 1714-1718.
  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. Роль негемового заліза у протекторній дії екдистерону на розвиток стрептозотоциніндукованої 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. Реутов В.П., Сорокина Е.Г., Охотин В.Е., Косицын Н.С. Циклические превращения оксида азота в ор­ганизме млекопитающих. -М.: Наука, 1998. - 159 с.
  9. 9. Akerman K.E.O., Wikstrom M.K.F. Safranine as a probe of the mitochondrial membrane potential // FEBS Lett. - 1976. - 68, №2. - P. 191-197.
  10. 10. Akopova O.V., Kolchinskaya L.I., Nosar V.I., Smirnov A.N., Malysheva M.K., Mankovska I.N., Sagach V.F. The effect of mitochondrial permeability transition pore opening on reactive oxygen species production in rat brain mitochondria // Укр. біохім. журн. - 2011. -83, № 6 - P. 46-55.
  11. Brand M.D., Affourtit Ch., Esteves T.C., Green K., Lambert A.J., Miwa S., Pakay J., Parker N. Mitochon­drial superoxide: production, biological effects, and activation of uncoupling proteins // Free Rad. Biol. Med. -2004. - 37, №6. - P. 755-767.
  12. Basaga H.S. Biochemcal aspects of free radicals //Cell Biol. - 1990. - 68, №5. - P. 989-998.
  13. Blaustein M.P. Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness //Amer. J. Physiol. - 1993. - 264. -P. C1367-C1387.
  14. Borutaite V., Brown G.C. S-nitrosothiol inhibition of mitochondrial complex I causes a reversible increase in mitochondrial hydrogen peroxide production // Biochim. and Biophys. Acta. - 2006. - 1757. - P. 562-566.
  15. Boyde T.R., Rahmatullah M. Optimization of conditions for the colorimetric determination of citrul-line using diacetyl monoxime // Anal. Biochem. - 1980. -107, №2. - P. 424-431.
  16. Brookes P.S., Yoon Y., Robotham J.L., Anders M.W., Sheu Sh.-Sh. Calcium, ATP, and ROS: a mitochondrial love-hate triangle // Amer. J. Physiol. - 2004. - 287. -C817-C833.
  17. 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.
  18. McCormak J.G., Denton R.M. Mitochondrial Ca2+ transport and the role of intramitochondrial Ca2+ in the regulation of energy metabolism // Dev. Neurosci. -1993. - 15. - P. 165-173.
  19. 19. Daiber A., Wenzel P., Oelze M. 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.
  20. 20. 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.
  21. Halliwell B. Oxidants and human disease: some new concepts // FASEB J. - 1987. - 1, № 5. - P. 358-364.
  22. Hoppe U.C. Mitochondrial calcium channels // FEBS Lett. - 2010. - 584. - P. 1975-1981.
  23. Huwiler M., Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase/H O /iodide system // Eur. J. Biochem. - 1984. - 141, № 1. - P.2 69-74.
  24. 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.
  25. Kakkar P., Singh B.K. Mitochondria: a hub of redox activities and cellular distress control // Mol. Cell Biochem. - 2007. - 305. - P. 235-253.
  26. Korshunov S.S., Skulachev V.P., Starkov A.A. High protonic potential actuates a mechanism of produc­tion of reactive oxygen species in mitochondia //FEBS Lett. - 1997. - 416 - P. 15-18.
  27. Kroemer G., Petit P., Zamzami N., Vayssiere J.-L., Mignotte B. The biochemistry of programmed cell death //FASEB J. - 1995. - 9. - P. 1277-1287.
  28. Lacerda L., Smith R.M., Opie L., Lecour S. TNF6-induced cytoprotection requires the production of free radicals within mitochondria in C2C12 myotubes // Life Sci. - 2006. - 79. - P. 2194-2201.
  29. 29. Radi R., Beckman J.C., Bush K.M., Freeman B.A. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide // Arch. Biochem. and Biophys. - 1991. - 288. - P. 481-487.
  30. 30. Rizzuto R., Bernardi P., Pozzan T. Mitochondria as all-round players of the calcium game // J. Physiol. -2000. - 529, №1. - P. 37-47.

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