The role of mitochondria in NO-dependent regulation of Na+, K+ -ATP activity in the rat aorta
Akopova OV, Kotsiuruba AV, Kharlamova OM, Korkach IuP, Sahach VF
- O.O. Bogomoletz Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv, Ukraine
- A.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz56.04.076
Abstract
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.
Keywords:
Na+, K+ -ATPase, aorta, Ca2+-uptake, heart mitochondria, ROS, RNS, oxidative damage
References
- Akopova OV, Kotsyuruba AV, Tkachenko YP, Sagach VF Nitric oxide inhibits the opening of the mitochondrial pore and increases the calcium capacity of the mitochondria in vivo . Fiziol zh. 2005. 51, N 3. p. 3-11.
- Akopova OV, Kharlamova OM, Kotsyuruba AV, Ko + kach Yu.P., Sagach VF The influence of nitric oxide on Na, K + ATPase in the aortic tissue of rats . Fiziol zh. 2009. 55, N 1. p. 27-35.
- Akopova O.V. Rol' mitohondrial'noi pori v transmembrannom obmene kal'tsiya v mitohondriyah . . Ukr.biohim. zhurn. 2008. 80, N 3. S.40-47.
- Boldirev A.A. Na+, K+-ATRaza kak oligomernii ansambl' .Biohimiya. 2001. 66. S.1013-1025.
- Vanin A.F. Dinitrozil'nie kompleksi zheleza i S-nitrozotioli dve vozmozhnie formi stabilizatsii i transporta oksida azota v biologicheskih sistemah . Biohimiya, 1998. 63, N 7. S.924-938.
- Korkach Yu.P., Dudchenko N.O., Kotsyuruba A.V., Prisyazhna O.D., Sagach V.F.. Rol' negemovogo zaliza u protektornii dii ekdisteronu na rozvitok streptozototsin-indukovanoi gipoglikemii u shchuriv . Ukr.biohim. zhurn. 2008. 80, N 1. S.46-51.
- Kostyuk P.G., Kostyuk O.P., Luk'yanets' O.A. Calcium ions in brain function from physiology to pathology. K.: Nauk. dumka. 2005. 198 p.
- Skulachev V.P. Energetika biologicheskih membran. M.: Nauka, 1989. 564 s.
- 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.
CrossRef
PubMed
- Basaga H.S. Biochemcal aspects of free radicals .Cell Biol. 1990. 68,N 5. P.989-998.
CrossRef
PubMed
- Blaustein M.P. Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness . Amer. J. Physiol. 1993. 264. P. C1367-C1387.
CrossRef
PubMed
- Brown G.C. Nitric oxide and mitochondrial respiration .Biochim. Biophys. Acta. 1999. 1411. P.351-369.
CrossRef
- 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,N 9. P.5125-5130.
CrossRef
PubMed
- 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, N 1-3. P. 40-47.
CrossRef
PubMed
- 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.
CrossRef
PubMed
- Green L.C., David A.W., Glogovski J. Analysis of nitrate, nitrite and [15N]nitrate in biological fluids . Anal. Biochem. 1982. 126, N 1. P.131-138.
CrossRef
- Huwiler M., Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase. HO. iodide system . Eur. J. Biochem., 1984. 141, N 1. P. 69-74.
CrossRef
PubMed
- Ignarro L.J., Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide . Circulat. Res. 2002. 90, N 1. P.21-28.
CrossRef
PubMed
- Lander H.M. An essential role for free radicals and derived species in signal transduction . FASEB J. 1997. 11. P.118-124.
CrossRef
PubMed
- 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, N 22. P.1 1954-11959.
CrossRef
PubMed PubMedCentral
- 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, N 6. P.3465-3470.
CrossRef
PubMed
- Rizzuto R., Bernardi P., Pozzan T. Mitochondria as all-round players of the calcium game . J. Physiol., 2000. 529, N 1. P. 37-47.
CrossRef
PubMed PubMedCentral
- 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.
CrossRef
PubMed
- 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, N 8. P.1919-1921.
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