Ucp2 and ucp3 genesexpression, heart function and oxygen cost of myocardial work changes during agingand 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.
References
- Костерин С.А., Браткова Н.Ф., Курский М.Д. Роль сарколеммы и митохондрий в обеспечении кальциевого контроля расслабления миометрия // Биохимия. - 1985. - 50, №8. - С. 1350-1361.
- Сагач В.Ф., Вавілова Г.Л., Струтинська Н.А., Рудик О.В. Старіння підвищує чутливість до індукторів мітохондріальної пори в серці щурів // Фізіол. журн. - 2004. - 50, №2. -С 49-63.
- Сагач В.Ф., Рудик О.В., Вавілова Г.Л. та ін. Мелатонін відновлює ішемічну толерантність і зменшує чутливість відкривання мітохондріальної пори в серці старих щурів // Фізіол. журн. - 2006. -52, №3. -С 3-14.
- Сагач В.Ф., Шиманська Т.В., Надточій С.М. Фактор,який вивільнюється під час реперфузії ішемізованого серця, може бути маркером відкриття мітохонд-ріальної пори // Фізіол. журн. - 2003. - 49, №4. -С 6-12.
- Терешина Е.В. Роль жирных кислот в развитии возрастного окислительного стресса. Гипотеза // Успехи геронтологии. - 2007. - 20, №1. - С. 59-65.
- 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.
- 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.
- 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.
- Cannon B., Nedergaard J. Brown adipose tissue: function and physiologicsl significance // Physiol. Rev. -2004. - 84. - P. 277-359.
- 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.
- Crompton M. The mitochondrial permeability transition pore and its role in cell death // Biochem. J. - 1999. -341. - P. 233-249.
- Crompton M., Barksby E., Johnson N., Capano M. Mitochondrial intermembrane junctional complexes and their involvement in cell death // Biochimie. - 2002. -84. - P. 143-152.
- 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.
- Griffiths E., Halestrap A. Mitochondrial non specific pores remain closed during cardiac ischaemia but open upon reperfusion // Biochem. J. - 1995. - 307. - P. 93-98.
- Halestrap A, Mcstay G., Clarke S. The permeability transition pore complex: another view // Biochemie. -2002. - 84. - P. 153 - 166.
- 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, № 1.- P. 265-275.
- 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.
- 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.
- Nadtochiy S.M., Nauduri D., Shimanskaya T.V. et al. Purine release: a protective signaling mechanism of the mitochondrial permeability transition pore in ischemia // Фізіол. журн. - 2008. - 54, №6. - С. 5-14.
- Phaneuf S., Leeuwenburgh С 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.
- Sack M.N. Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance // Cardiovasc. Res. - 2006. - 72. - P. 210 - 219.
- 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.
- 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.
- 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, №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, №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.
- 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, №3. - P. 833-45.
|