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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. 2005; 51(3): 18-24

The investigation of mithochondrialpermeability transition pore (mptp) inthe development of myocardial andvascular contractility disfunctions

A.V. Dmitrieva, V.F. Sagach, A. Yu. Boguslavsky

    A.A. Bogomoletz Institute of Physiology National Academy ofSciences of Ukraine, Kiev



Abstract

In experiments on the isolated myocardial and vascular preparations the role of the mithochondrial permiability tran- sition pore (mPTP) in the development of reperfusion injury was investigated. Co-perfusion of the previously activated myocardial trabecula (МТ) and arterial rings (AR) by solution collected during the first 5 min of isolated heart reperfusion, caused a sharp and significant decrease of tonic tension of both isolated preparations. Besides the significant inhibition of the МТ and АR reactions after electrical stimulation, modulation of AR reaction by the influence of MT is also registered. The solution collected at first minutes of heart reperfusion, pre- serve a dilation property within 24 hours of storage at room temperature. Preliminary perfusion of МТ and АR with methylen blue (МB, 10-4 М/l) or the addition to the solution dithiothreitol (DTT, 2.10-5 М/l) and diethyl maleate (DEM, 2.10-5 М/l) resulted in an almost complete inhibition of this dilatation influence on the isolated preparations. The data received testify that the solution comprise a NO-containing substance, possible nitrosoglutation. Pre-incubation (2 min) МТ in a solution with mPTP activator phenylarsine oxide (PAO, 10-5 М/l) and subsequent reperfusion with a control solution resulted in deep and irreversible decrease of tonic tension and inhibition of contractility of both isolated prepa- rations. The received data are qualitatively similar to results described above. Our data and results received in additional experiments on isolated mitochondria allow us to assert that solution flowing from the ischemized heart contains the stable mitochondrial factor (SMF) with a significant dilatation prop- erty. An addition of МB and DEM in the reperfusion solution abrogated its dilation influence. Co-perfusion (10 min) of the injured МТ and АR by the solution with nitrosoglutation (10- 5 М/l) restored normal contractility of the isolated prepara- tions and modulation of the AR reaction by the influence of MT. It once again confirms the presence of an NO-containing substance in the SMF content. Thus, the mPTP activation plays the key role in the development of myocardial reperfusion injury and results in release of SMF, which can be the basic agent of paracrine regulation of myocardial contractility, coronary and peripheral vessels tone.

Full text: (PDF, in Ukrainian)

References

  1. Жукова А. В. Модулюючий вплив ендотеліальногорелаксуючого фактора на реактивність міокарда таартеріальних судинних смужок // Фізіол. журн. –1999. – 45, № 1–2. – С. 64–72.
  2. Сагач В.Ф., Вавілова Г.Л., Струтинська Н.А., Ако-пова О.В. Вплив індукторів та інгібіторів мітохонд-ріальної пори на її утворення та на вивільненнянеіндентифікованого мітохондріального фактора //Там само. – 2003. – 49, №1. – С. 3–12.
  3. Сагач В.Ф., Дмитрієва А.В., Шиманська Т.В.,Надточій С.М. Фактор, який вивільнюється під часреперфузії ішемізованого серця, дослідженнявпливу на міокард, коронарні та периферичнісудини // Там само. – 2002. – 48, №1. – С. 3–8.
  4. Сагач В.Ф., Шиманська Т.В., Надточій С.М. Фактор,який вивільнюється під час реперфузії ішемізова-ного серця, може бути маркером відкриттямітохондріальної пори // Там само. – 2003. – 49,№ 4. – С. 7–13.
  5. Bolli R., Bhatti Z.A., Tang X.L., Qiu Y.M. Evidencethat late preconditioning against myocardial stanningin conscious rabbits triggered by the generation of ni-tric oxide // Circulat.Res. – 1997. – 81, № 1. – P.42–52.
  6. Borutaite V., Jekabsone A., Morkuniene R., BrownG.C. Inhibition of mitochondrial permiability transionprevent mitochondrial dysfunction, cytochrom c releaseand apoptosis inuced by heart ischemia // J.Mol.Cell.Cardiol. – 2003. – 35.–P. 357–366.
  7. Borutaite V., Morkuniene R., Brown G.C. Nitric oxidedonors, nitrosothiols and mitochondrial respirationinhibitors induce caspase activation by different mecha-nisms // FEBS Lett. – 2000. – 467. – P. 155–159.
  8. Crompton M. The mitochondrial permeability transi-tion pore and its role in cell death // Biochem. J. –1999. – 341. – P. 233–249.
  9. 9. Crompton M., Andreeva L. On the involvement of amitochondrial pore in reperfusion injury // Bas. Res.Cardiol. – 1993. – 88. – P. 513–523.
  10. 10. Flaherty J., Weisfeldt M. Reperfusion injury // FreeRadic. Biol. And Med. – 1988. – 5, №5–6. – Р. 409–419.
  11. Jekabsone A., Dapkunas Z., Brown G.C., Borutaite V.S-Nitrosothiol-induced rapid cytochrom c release,caspase activation and mitochondrial permiabilitytransition in perfused heart // Biochem. Pharmacol. –2003. – 66. – Р. 1513–1519.
  12. Korge P., Goldhaber J.I., Weiss J.N. Phenylarsine ox-ide induced mitochondrial permeability transition,hypercontracture, and cardiac cell death // Amer. J.Physiol. – 2001. – 280. – P. H2203–H2213.
  13. Lefer A.M. Significance of lipid mediators in shockstates // Circulat. Shock. – 1989. – 27. – P. 3–12.
  14. Mayer B., Pfeiffer S., Schrammel A. et al. A new pathway ofnitric oxide/cyclic GMP signaling involving S-nitrisogluta-tione // J. Biol. Chem. – 1998. – 273, №6. – P. 3264–3270.
  15. Murphy A. Mitochondria in human disease // The Bio-chemist. – 2000. – 4. – P. 29–34.
  16. Sastre J., Pallardo F.V., Vina J. Mitochondrial oxida-tive stress play a key role in aging and apoptosis //Life. – 2000. – 49. – P. 427–435.
  17. Stamler J.S., Jaraki O., Osborn J. et al. Nitric oxidecirculates in mammalian plasma primary as an S–nitrosoadduct of serum albumin // Proc. Natl. Acad USA. –1992. – 89. – 7674–7677.
  18. Stefen M., Sarkela T.M., Gubina A.A. et al. Methabo-lism of nitrosoglutatione in intact mitоchondria //Biochem. J. – 2001. – 356. – P. 395–402.
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