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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. 2011; 57(4): 34-45

Mitochondria permeability transition as a target for ischemic preconditioning

Hoshovs'ka IuV, Shymans'ka TV, Rudyk OV, Korkach IuP, Sahach VF

    О.О. Bogomolets Institute of Physiology, National Akademy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz57.04.034


Abstract

The ischemic preconditioning (IPC) limits myocardial injury provoked by a subsequent prolonged ischemia-reperfusion (I/R). The underlying mechanisms of enhanced resistance of heart are actively studied, but for sure it was established that mito­chondria play a major role in IPC-stimulated adaptation to ischemia. In this article we present and discuss evidences that cardioprotective effect of IPC is mediated by inhibition of mitochondria permeability transition pore (MPTP) opening. It was shown that IPC effectively prevents the excessive pro­duction of ROS by mitochondria during I/R and promotes a more complete restoration of function of isolated rat hearts. It was revealed that MPTP formation due to I/R was inhibited in IPC heart. Mitochondrial factor, the marker of MPTP open­ing found in outflow probes, was released in much lesser amounts in IPC hearts that in non-IPC. Furthermore, mito­chondria isolated from IPC hearts showed a decreased sensi­tivity to calcium ions, a MPTP inductor, and, thus, massive MPTP-depended swelling of mitochondria was abrogated in IPC hearts. In our experiments we observed slight increase in inducible NOS activity right after short ischemic stimuli. We suppose that increased NO production by iNOS is involved in inhibition of MPTP and this may be one of the possible mecha­nisms of decreased sensitivity of mitochondria to calcium ions. It is concluded that among the processes involved in formation of cardioprotective effect of IPC, a reduction of membrane permeability due to the inhibition of MPTP opening plays a crucial role.

Keywords: isolated heart, ischemic precondition, nitric oxide,iNOS, MPTP

Full text: (PDF, in Ukrainian)

References

  1. Garmatina O.Yu., Tkachenko MN, Moibenko AA Inducible nitric oxide synthase in heart pathology . Journal. AMS of Ukraine. 2005. 11, No. 4. P. 645-659.
    2.  
  2. Kosterin SA, Bratkova NF, Kursky M.D. The role of sarcolemma and mitochondria in providing calcium control of myometrial relaxation . Biochemistry. 1985. 50, N 8. P. 1350-1361.
    3.  
  3. Petrischev N.N., Shlyakhto V.E., Tsyrlin E.A. The role of free oxygen radicals in mechanisms of local and distant ischemic myocardial preconditioning . Vestnik Ross. Acad. honey. Sciences. 2006. N 8. pp. 10-15.
    4.  
  4. Sahach VF, Shymans'ka TV, Nadtochyĭ SN [The role of nitric oxide in changes in the oxygen consumption and the oxygen cost of the work of the cardiac muscle]. . Fiziol. Zh. - 2000. 46, N 2. P. 33-40.
    5.  
  5. Sahach VF, Vavilova HL, Rudyk OV, Strutyns'ka NA. [Release of unidentified substances of mitochondrial origin--evidence of mitochondrial permeability transition pore opening in the heart mitochondria of rats ]. . Fiziol. Zh. 2003. 49, N 5. pp. 3-12.
    6.  
  6. Sahach VF, Shimans'ka TV, Nadtochiĭ SM. Protection of the heart from reperfusion injury and ineffective oxygen using inhibitors of the mitochondrial permeability transitional pore. . Fiziol. Zh. - 2002. 48, N 6. P. 3-10.
    7.  
  7. Sahach VF, Shymans'ka TV, Nadtochiĭ SM. Factor released during myocardial ischemia reperfusion may become a marker of opening of the mitochondrial permeability transition pore. . Fiziol. Zh. - 2003. 49, N 4. p. 7-13.
    8.  
  8. Shabalin AV Nikitin Yu.P. Cardio-myocyte protection. Current status and prospects . Cardiology. 1999. N 3. pp. 4-10.
    9.  
  9. Shevchenko Yu.L., Karpishchenko AI, Belevitin AB, Svistov AS, Demidov ON, Tyrenko VV Autoinduced myocardial tolerance to ischemia: the role of stress proteins in mechanisms of its occurrence . Human physiology. 1999. 25, No. 1. P. 134-139.
    10.  
  10. Shimanskaya TV, Dobrovolsky FV, Vavilova GL, Strutinskaya NA, Rudyk EV, Sagach VF NO-dependent modulation of the sensitivity of mitochondrial pore opening in ischemia . reperfusion of the isolated heart . Ross. physiol. . them. I.M. Sechenov. 2009. 95, N 1. P. 28-37.
    11.  
  11. Shugaley B.C., Kozina A.S. Urea content and arginase activity in rat organs during acclimatization to cold . Fiziol. . USSR. 1977. 8. pp. 1199-1202.
    12.  
  12. Bolli R. Cardioprotective function of inducible nitric ox­ide synthase and role of nitric oxide in myocardial is­chemia and preconditioning: an overview of a decade of research . J. Mol. Cell Cardiol. 2001. 33. P. 1897-1918. CrossRef PubMed
    13.  
  13. Borutaite V., Morkuniene R., Brown G.C. Release of cytochrome c from heart mitochondria is induced by high Ca2+ and peroxynitrite and is responsible for Ca(2+)-induced inhibition of substrate oxidation . Biochim. Biophys. Acta. 1999. 1453, N 1. P. 41-48. CrossRef  
  14. Boyde T.R, Rahmatullah M. Optimization of conditions for the colorimetric determination of citrul-line, using diacetyl monoxime . Anal. Biochem. 1980. 107, N 2. P. 424-431. CrossRef  
  15. Brand M.D., Buckingham J.A., Esteves T.C., Green K., Lambert A.J., Miwa S., Murphy M.P., Pakay J.L., Tal­bot D.A., Echtay K.S. Mitochondrial superoxide and ag­ing: uncoupling-protein activity and superoxide produc­tion . Biochem. Soc. Symp. 2004. 71. P. 203-213. CrossRef PubMed
    16.  
  16. Brookes P.S., Salinas E.P., Darley-Usmar K., Eiserich J.P., Freeman B.A., Darley-Usmar V.M., Anderson P.G. Concentration-depend effect of nitric oxide on mito­chondrial permeability transition and cytochrom C release . J. Biol. Chem. 2000. 275, N 27. P. 20474-20479. CrossRef PubMed
    17.  
  17. Burwell L.S., Brookes P.S. Mitochondria as a target for the cardioprotective effects of nitric oxide in is-chemia-reperfusion injury . Antioxid. Redox Signal. 2008. 10, N 3. P. 579-599. CrossRef PubMed
    18.  
  18. Chen Q., Hoppel C. L. Ischemia reperfusion injury in the aged heart: role of mitochondria . Arch. Biochem. Biophys. 2003. 420. P. 287-297. CrossRef PubMed
    19.  
  19. Choksi K. B., Papaconstantinou J. Age-related alter­ations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes . Free Rad. Biol. Med. 2008. 44. P. 1795-1805. CrossRef PubMed PubMedCentral
    20.  
  20. Crompton M. The mitochondrial permeability transi­tion pore and its role in cell death . Biochem. J. 1999. 341. P. 233-249. CrossRef PubMed PubMedCentral
    21.  
  21. Dedkova EN, Blatter LA. Characteristics and function of cardiac mitochondrial nitric oxide synthase . J. Physiol. 2009. 587. N 4. 851-572. CrossRef PubMed PubMedCentral
    22.  
  22. Echtay K.S., Roussel D., St-Pierre J., Morrison A., Pickering S., Clapham J.C., Brand M.D. Superoxide activates mitochondrial uncoupling protein . Nature. 2002. 415. P. 96-99. CrossRef PubMed
    23.  
  23. Fisher S. G., Marber M. S. An in vivo model of is-chemia-reperfusion injury and ischaemic preconditioning in the mouse heart . J. Pharmacol. Toxicol. Methods 2002. 48. P. 161-169. CrossRef  
  24. Garlid K.D., Paucek P., Yarov-Yarovoy V., Murray H.N., Darbenzio R.B., D'Alonzo A.J., Lodge N.J., Smith M.A., Grover G.J. Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP_sensitive K+channels. Possible mechanisms of cardioprotection . Circ. Res. 1997, N 81. P. 1072-1082. CrossRef PubMed
    25.  
  25. Gopalakrishna R, Anderson WB. Ca2+- and phospho-lipid-independent activation of protein kinase C by selective oxidative modification of the regulatory do­main . Proc. Natl. Acad. Sci. U. S. A. 1989. 86. P. 6758-6762. CrossRef PubMed PubMedCentral
    26.  
  26. Green L.C., Wagner D.A., Glogowski J., Skipper P.L., Wishnok J.S., Tannenbaum S.R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids . Anal. Biochem. 1982. 126, N 1. P. 131-138. CrossRef  
  27. Griffiths E., Halestrap A. Mitichondrial non specific pores remain closed during cardiac ischaemia but open upon reperfusion . Biochem. J. 1995. 307. P. 93-98. CrossRef PubMed PubMedCentral
    28.  
  28. Halestrap A., Clarke S.J., Javadov S.A. Mitochondrial permeability transition pore opening during myocar­dial reperfusion a target for cardioprotection . Cardiovasc. Res. 2004. 61. P. 372-385. CrossRef  
  29. Halestrap A.P., Clarke S.J., Khaliulin I. The role of mitochondria in protection of the heart by precondi­tioning . Biochim. Biophys. Acta. 2007. 1767, N 8. P. 1007-1031. CrossRef PubMed PubMedCentral
    30.  
  30. Han H.G., Wang Z.W., Zhang N.B., Zhu H.Y Role of nitric oxide during early phase myocardial ischemic preconditioning in rats . Chin. Med. J. (Engl). 2008. 121, N 13. P. 1210-1214. CrossRef PubMed
    31.  
  31. Hausenloy D.J., Maddock H. L., Baxter G.F., Yellon D.M. Ingibiting mithochondrial permeability transition pore opening: a new paradigm for myocardial precon-ditiong? . Cardiovasc. Res. 2002. 55. P. 534-543. CrossRef  
  32. Heger J., G4decke A., Flrgel U., Merx M.W., Molojavyi A., Kbhn-Velten W.N., Schrader J. Cardiac-specific overexpression of inducible nitric oxide synthase does not result in severe cardiac dysfunction . Circ. Res. 2002. 90. P. 93-99. CrossRef PubMed
    33.  
  33. Humphries K.M., Yoo Y, Szweda L.I. Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2-nonenal . Biochem. 1998. 37, N 2. P. 552-557. CrossRef PubMed
    34.  
  34. Huwiler M., Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase. H O . io­dide system . Eur. J. Biochem. 1984. 141. 2N 2 1. P. 69-74. CrossRef PubMed
    35.  
  35. Javadov S. A., Clarke S., Das M., Griffiths E.J., Lim K.H.H., Halestrap A.P. Ischaemic preconditioning in­hibits opening of mithochondrial permeability transi­tion pores in the reperfused rat heart . J. Physiol. 2003. 549. P. 513-524. CrossRef PubMed PubMedCentral
    36.  
  36. Kanno S., Lee P., Zhang Y, Ho C, Griffith B.P., Shears L.L.2nd, Billiar T.R. Attenuation of myocardial is-chemia. reperfusion injury by superinduction of indu­cible nitric oxide synthase . Circulation. 2000. 101. P. 2742-2748. CrossRef PubMed
    37.   Kuthan H., Ullrich V., Estabrook R.W. A quantitative test for superoxide radicals produced in biological  
  37. Kroemer G., Galluzzi L., Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol.Rev. 2007. 87. P. 99-163. CrossRef PubMed
    38.  
  38. Lesnefsky E.J., Gudz T.I., Migita C.T., Ikeda-Saito M., Hassan M.O., Turkaly P.J., Hoppel C.L. Ischemic injury to mitochondrial electron transport in the aging heart: damage to the iron-sulfur protein subunit of elec­tron transport complex III . Arch. Biochem. Biophys. 2001. 385. N 1. P. 117-128. CrossRef PubMed
    39.  
  39. Liu Y., Sato T., O'Rourke B., Marban E. Mitochon­drial ATP dependent potassium channels: novel effec­tors of cardioprotection . Circulation. 1998. N 97. P. 2463-2469. CrossRef PubMed
    40.  
  40. Murry C.E., Jennings R.B, Reimer K.A. Precondition­ing with ischemia: a delay of lethal cell injury in is­chemic myocardium . Ibid. 1986. 74. P. 1124-1136. CrossRef PubMed
    41.  
  41. Nadtochiy S.M., Nauduri D., Shimanskaya T.V., Sagach V.F., Brookes P.S. Purine release: a protective signal-ing mechanism of the mitochondrial permeability tran­sition pore in ischemia .Fiziol. zhurn. 2008. 54, N 6. S. 5-14.
    42.  
  42. Nair V., Cooper C.S., Vietti D.E., Turner G.A., The chemistry of lipid peroxidation metabolites: crosslin-king reactions of malondialdehyde . Lipids. 1986. 21. P. 6-10. CrossRef PubMed
    43.  
  43. Oshima Y., Fujio Y, Nakanishi T., Itoh N., Yamamoto Y, Negoro S., Tanaka K., Kishimoto T., Kawase I., Azuma J. STAT3 mediates cardioprotection against ischemia. reperfusion injury through metallothionein induction in the heart . Cardiovasc. Res. 2005. 65. P. 428-435. CrossRef PubMed
    44.  
  44. Pinkus R., Weiner L.M., Daniel V. Role of oxidants and antioxidants in the induction of AP-1, NF-kB, and glutathione S-transferase gene expression . J. Biol. Chem. 1996. 271. P. 13422-13429. CrossRef PubMed
    45.  
  45. Shimanskaya T.V. Goshovska Y, Sagach V. The role of mitochondrial permeability transition pore in modula­tion of oxygen cost of myocardial work by endogenous NO. Adv. Biomed. Res. (Cambridge). 2010. P.313-317.
    46.  
  46. Tsukahara H., Miura M., Tsuchida S., Hata I., Hata K., Yamamoto K., Ishii Y, Muramatsu I., Sudo M. Effect of nitric oxide synthase inhibitors on bone me­tabolism in growing rats . Amer. J. Physiol. 1996. 270. N 5, Pt 1. P. E840-E845. CrossRef PubMed
    47.  
  47. Van den Hoek T.L., Becker L.B., Shao Z., Li C, Schumacker P.T. Reactive oxygen species released from mitochondria during brief hypoxia induce precondi­tioning in cardiomyocytes . J. Biol. Chem. 1998. 273. P. 18092-18098. CrossRef PubMed
    48.  
  48. West M.B., Rokosh G., Obal D., Velayutham M., Xuan Yu-Ting, Hill B., Keith R., Schrader J., Guo Y, Conklin D., Prabhu S., Zweier J., Bolli R., Bhatnagar A. Cardiac myocyte-specific expression of inducible nitric oxide synthase protects against ischemia. reperfusion injury by preventing mitochondrial permeability transition . Circulation. 2008. 118. P. 1970-1978. CrossRef PubMed PubMedCentral
    49.  

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