Українська English

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. 2009; 55(3): 26-36

UCP2 AND UCP3 GENES EXPRESSION, HEART FUNCTION AND OXYGEN COST OF MYOCARDIAL WORK CHANGES DURING AGING AND ISCHEMIA-REPERFUSION

Y.V. Goshovska, I.I. Lisovyi, T.V. Shimanskaya, V.F. SagacH.

    O.O. Bogomoletz Institute of Physiology NationalAcademy Sciences of Ukraine, Kyiv


Abstract

To examine the effects of ischemia/reperfusion on UCPs genes expression, heart function and oxygen cost of myocardial work, hearts of adult (6 mo) and old (24 mo) rats were perfused by Langendorf preparation and subjected to 20 min ischemia fol­lowed by 40 min reperfusion. Mitochondrial permeability tran­sition due to ischemic stimuli was evaluated by release of mito-chondrial factor (lambda =250 nm) which was previously shown as a marker of MPTP opening. Expression of UCPs was detected by reverse transcriptional polymerase chain reaction. Mitochondrial membrane potential (dPhi m) and oxygen consumption in iso­lated heart mitochondria of adult and old rats were measured. It was shown that impaired function of aging rat hearts was ac­companied with an increased oxygen cost of myocardial work and lower mitochondrial membrane potential compared with adult rats. Reperfusion disturbances of cardiodynamic, contractile activity of myocardium and noneffective oxygen utilization in early period of reperfusion were less intensive in aged hearts than in adult ones. Therefore, the levels of mRNA of UCP2 in aging hearts were higher and mRNA levels of UCP3 were tended to increase. At the same time ischemia/reperfusion increased the expression of UCP2 and UCP3 in adult myocardium: mRNA levels of UCPs were significantly higher that those in control, whereas there was no such effect in aging hearts. It is concluded that uncoupling proteins are implicated in the age-depended heart dysfunction and development of the pathological mechanisms during ischemia-reperfusion.

Keywords: ischemia/reperfusion, heart, UCPs genes

Full text: (PDF, in Ukrainian)

References

  1. Kosterin SA, Bratkova NF, Kursky MD The role of sarcolemma and mitochondria in providing calcium control of myometrial relaxation . Biochemistry. 1985. 50, N 8. P. 1350-1361.
  2. Sagach VF, Vavilova GL, Strutynska NA, Rudyk OV Aging increases the sensitivity to inducers of mitochondrial pores in the heart of rats . Fiziol Zh. magazine. 2004. 50, N 2. p. 49-63.
  3. Sagach VF, Rudyk OV, Vavilova GL etc. Melatonin restores ischemic tolerance and reduces the sensitivity of the opening of mitochondrial pores in the heart of old rats . Fiziol Zh. 2006. 52, N 3. p. 3-14.
  4. Sagach VF, Szymanska TV, Nadtochiy SM The factor that is released during the reperfusion of an ischemic heart can be a marker of the opening of the mitochondrial pore . Fiziol Zh. 2003. 49, N 4. p. 6-12.
  5. Tereshina EV The role of fatty acids in the development of age-related oxidative stress. Hypothesis . Advances in gerontology. 2007. 20, N 1. P. 59-65.
  6. Barazzoni R., Nair K.S. Changes in uncoupling protein-2 and 3 expression in aging rat skeletal muscle, liver, and heart . Amer. J. Physiol. Endocrinol. Metab. 2001. 280. P. E413-E419.
  7. Becker L.B., Vanden Hoek T.L., Shao Z-H. et al. Gen­eration of supeoxide in cardiomyocytes during ischemia before reperfusion . Amer. J. Physiol. 1999. 277. P2240-2246.
  8. Borutaite V., Mildaziene V., Brown G.C., Brand M.D. Control and kinetic analysis of ischemia-damaged heart mitochondria: which parts of the oxidative phosphoryla­tion system are affected by ischemia? . Biochim. Biophys. Acta 1995. 1272. P. 154-158.
  9. Brand M.D. Measurement of mitochondrial proton-motive force . Editors: Brown G.C., Cooper C.E. In: Bioenergetics: a practical approach. Oxford.: IRL Press. 1995. P. 39-62.
  10. Brand M.D., Esteves T. Physiological function of the mitochondrial uncoupling proteins UCP2 and UCP3 . Cell Met. 2005. 2. P. 85-93.
  11. Cannon B., Nedergaard J. Brown adipose tissue: func­tion and physiologicsl significance . Physiol. Rev. 2004. 84. P. 277-359.
  12. 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.
  13. Crompton M. The mitochondrial permeability transition pore and its role in cell death . Biochem. J. 1999. 341. P. 233-249.
  14. Crompton M., Barksby E., Johnson N., Capano M. Mitochondrial intermembrane junctional complexes and their involvement in cell death . Biochimie. 2002. 84. P. 143-152.
  15. Esteves T.C., Brand M.D. The reactions catalysed by the mitochondrial uncoupling proteins UCP2 and UCP3 . Biochim. Biophys. Acta. 2005. 1709. P. 35-44.
  16. Griffiths E., Halestrap A. Mitochondrial non specific pores remain closed during cardiac ischaemia but open upon reperfusion . Biochem. J. 1995. 307. P. 93-98.
  17. Halestrap A, Mcstay G., Clarke S. The permeability transition pore complex: another view . Biochemie. 2002. 84. P. 153 166.
  18. Hausenloy D.J., Maddock H.L., Baxter G.F., Yellon D.M. Ingibiting mithochondrial permeability transi­tion pore opening: a new paradigm for myocardial precondition? . Cardiovasc. Res. 2002. 55. P. 534-543.
  19. Hausenloy D., Yellon D.M. The mitochondrial perme­ability transition pore: its fundamental role in mediating cell death during ischemia and reperfusion. J. Mol. Cell. Cardiol. 2003. 35. P. 339-341.
  20. Lowry O.H., Rosenbrough N.J., Farr A.L. Protein measurement with the Folling phenol reagent . J. Biol. Chem. 1951. 193, N 1. P. 265-275.
  21. Murray A.J., Cole M.A., Lygate C.A. et al. Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart . J. Mol. Cell. Cardiol. 2008. 44. P. 694-700.
  22. Nadtochiy S.M., Tompkins A., Brookes P.S. Different mechanisms of mitochondrial proton leak in ischemia. reperfusion injury and precondition: implications for pa­thology and cardioprotection . Biochem. J. 2006. 395. P. 611-618.
  23. Nadtochiy S.M., Nauduri D., Shimanskaya T.V. et al. Purine release: a protective signaling mechanism of the mitochondrial permeability transition pore in ischemia . Fiziol. zhurn. 2008. 54, N 6. S. 5-14.
  24. Phaneuf S., Leeuwenburgh S Cytochrome c release from mitochondria in the aging heart: a possible mecha­nism for apoptosis with age .Amer. J. Physiol. Regul. Integr. Comp. Physiol. 2002. 282. P. R423-R430.
  25. Sack M.N. Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance . Cardiovasc. Res. 2006. 72. P. 210 219.
  26. Sastre J., Millan A., Garcia dlA. et al. Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by protecting against oxidative stress . Free Rad. Biol. Med. 1998. 24. P. 298-304.
  27. Sen T., Sen N., Jana S. et al. Depolarization and cardilipin depletion in aged rat brain mitochondria: relationship with oxidative strees and electron transport chain activity . Neurochem. Int. 2007. 50. P. 719-725.
  28. Serviddio G., Romano A.D., Tamborra R. et al. Bioen­ergetics in aging: mitochondrial proton leak in aging rat liver, kidney and heart . Redox. Rep. 2007. 12, N 1. P. 91-95.
  29. Stuart J.A., Brindle K.M., Harper J.A., Brand M.D. Mitochondrial proton leak and the uncoupling proteins . J. Bioenerg. Biomembr. 1999. 31, N 5. P. 517-525.
  30. West M.B., Rokosh G., Obal D. et al. 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.
  31. Young M.E., Patil S., Ying J. et al. Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor (alpha) in the adult rodent heart . FASEB J. 2001. 15, N 3. P. 833-45.
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2022.