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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(6): 38-45

Genipin--uncoupling protein inhibitor--reduces the protective effect of ischemic preconditioning

Hoshovs'ka IuV, Shymans'ka TV, Sahach VF

    Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz57.06.038


Abstract

The functional significance of uncoupling proteins UCP2 and UCP3 in the cell and the organism remains unknown. There have been reports about their involvement in cellular protec­tion mechanisms underlying the phenomenon of ischemic pre­conditioning. The purpose of this study was to elucidate the role of uncoupling proteins UCP2 and UCP3 in the formation of cardioprotective effect of ischemic preconditioning. In ex­periments on isolated rat hearts we show here an increase in the level of UCP2 and UCP3 gene expression in the heart tissue under the influence of ischemic preconditioning with three episodes of 5 min stopping the flow perfusion. Similar effects were induced by a prolonged ischemia-reperfusion of myocardium. The blockade of the UCP2 activity by genipin (Wako Inc, USA, 10-5 mol/L, isolated heart perfusion for 15 minutes) abolished the protective effect of adaptation to is­chemia. It was concluded that uncoupling proteins take part in the cardioprotective effect of ischemic preconditioning.

Keywords: изолированное сердце, разобщающиебелки UCP2 и UCP3, генипин, ишемическое преконди-ционирование.

Full text: (PDF, in Ukrainian)

References

  1. Galaguza M.M. Role of reactive oxygen species in mechanisms of local and distant ischemic myocardial preconditioning . Region. Circulation and microcirculation. 2005. 4, N 16. p. 72-78.
    2.  
  2. Goshovskaya Yu.V., Lisovyi OO, Shimanska TV, Sagach VF Changes of UCP2 and UCP3 gene expression, functional status and oxygen cost of myocardial work in conditions of aging and ischemia-reperfusion . Fiziol Zh. 2009. 55, N 3. p. 26-36. CrossRef  
  3. Goshovskaya Yu.V., Shimanska TV, Sagach VF The influence of genipin, a UCP2 inhibitor, on the function of the heart of old rats . Fiziol Zh. 2009. 55, N 5. p. 28-34.
    4.  
  4. Goshovskaya YV, Shimanska TV, Rudik OV, Korkach YP, Sagach VF Permeability of mitochondrial membranes as targets of ischemic preconditioning . Fiziol Zh. 2011. 57, N 4. p.
    5.  
  5. Sagach VF, Shimanska TV, Nadtochy SM Prevention of postperfusion disorders of cardiac function and ineffective use of oxygen by mitochondrial pore inhibitors . Fiziol Zh. 2002. 48, N 6. p. 3-9.
    6.  
  6. Sagach VF, Shimanska TV, Nadtochy SM The factor released during reperfusion of the ischemic heart may be a marker of mitochondrial pore opening . Fiziol Zh. 2003. 49, N 4. pp. 6-12. 
    7.  
  7. Barrier A., Olaya N., Chiappini F., Roser F, Scatton O., Artus C., Franc B., Dudoit S., Flahault A, Debuire B., Azoulay D., Lemoine A. Ischemic preconditioning modulates the expression of several genes, leading to the overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia-reperfusion . FASEBJ. 2005. 19. P. 1617-1626. CrossRef PubMed
    8.  
  8. 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
    9.  
  9. Brand M.D., Esteves T.C. Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3 . Cell Metabol. 2005. 2. P.85-93. CrossRef PubMed
    10.  
  10. Carreira R.S., Miyamoto S., DiMascio P., Goncalves L.M., Monteiro P., Providencia L.A., Kowaltowski A.J. Ischemic precondition enchances fatty acid-de­pendent mitochondrial uncoupling . J. Biochem. Bioenerg. 2007. 39. P. 313-320. CrossRef PubMed
    11.  
  11. 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
    12.  
  12. Garlid K.D., P. Paucek, V. Yarov-Yarovoy, Murray H.N., Darbenzio R.B., Lonzo A.J., Longe N.J., Smith M.A., Grover G.I. Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+channels. Possible mechanisms of cardioprotection . Circ.Res. 1997. 81. P. 1072-1082. CrossRef PubMed
    13.  
  13. 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
    14.  
  14. Koo H.J., Song Y.S., Kim H.J., Lee Y.H., Hong S.M., Kim S.J., Kim B.C., Jin C, Lim C.J., Park E.H. Antiin­flammatory effects of genipin, an active principle of gardenia . Eur. J. Pharmacol. 2004. 495. P. 201-208. CrossRef PubMed
    15.  
  15. Liu Y, T. Sato, B. O'Rourke, E. Marban. Mitochon­drial ATP dependent potassium channels: novel effec­tors of cardioprotection . Circulation. 1998. 97. P. 2463-2469. CrossRef PubMed
    16.  
  16. Liu Y, Chen L., Xu X., Vicaut E., Sercombe R. Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia. reperfusion and upregulate uncoupling protein-2 . BMC Physiol. 2009. 9. P. 17- 31. CrossRef PubMed PubMedCentral
    17.  
  17. Mattiasson G., Shamloo M., Gido G., Mathi K., Tomasevic G., Yi S., Warden C.H., Castilho R.F., Mel-her T., Gonzalez-Zulueta M. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunc­tion after storke and brain trauma . Nat. Med. 2003. 9. P. 1062-1068. CrossRef PubMed
    18.  
  18. Murray C.E., Jennings R.B, Reimer K.A. Precondi­tioning with ischemia: a delay of lethal cell injury in ischemic myocardium . Circulation. 1986. 74. P. 1124-1136. CrossRef PubMed
    19.  
  19. 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, 6. C.5-14.
    20.  
  20. Trenker M., Fertschai I., Malli R., Graier W.F. UCP2. 3 likely to be fundamental for mitochondrial Ca2+ uniport . Nature Cell Biol. 2008. 10, 11. P. 1237-1240. CrossRef  
  21. Tseng T.H., Chu C.Y, Huang J.M., Shiow S.J., Wang C.J. Crocetin protects against damage in rat primary hepatocytes.Cancer Lett. 1995. 97. P.61-67. CrossRef  
  22. Wu S.Y, Wang G.F., Liu Z.Q., Rao J.J., Lb L., Xu W., Wu S.G., Zhang J.J. Effect of geniposide, a hypogly­cemic glucoside, on hepatic regulating enzymes in dia­betic mice induced by a high-fat diet and streptozotocin . Acta Pharmacol Sin. 2009. 30, 2. P. 202-208. CrossRef PubMed PubMedCentral
    23.  
  23. Young M.E., Patil S., Ying J., Depre C, Ahuja H.S., Shipley G.L., Stepkowski S.M., Davies P.J., Taeg-tmeyer H. Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor (alpha) in the adult rodent heart . FASEB J.-2001. 15, 3. P.833-845. CrossRef PubMed
    24.  
  24. Zhang Ch.-Y, Parton L.E., Ye C.P., Krauss S., Shen R., Lin C.T., Porco J.A.Jr., Lowell B.B. Genipin inhibits UCP2-mediated proton leak and acutely reverses obe­sity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets . Cell Metab. 2006. 3, 6. P. 417-427. CrossRef PubMed
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