Українська Русский 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. 2006; 52(1): 41-48


The cardioprotective effect of heme oxygenase-1overexpression

T.V. Kukoba, Kotsuruba, A.A. Moibenko

    О.О. Bogomolets Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv


Abstract

The purpose of this study was to determine the protective effects of heme oxygenase-1 (HO-1) expression against pos- tischemic myocardial dysfunction. We also investigated HO-1 expression in cardiac tissue from the left and right ventricles of myocardium. Rat hearts were isolated and perfused according to Langendorff technique to evaluate the recovery of myocar- dial function after 20 min of global ischemia and 40 min of reperfusion. We found that HO-1 expression was more ex- pressed in left ventricles of myocardium in basic conditions and after ischemia/reperfusion as well as after its previous induction by hemin. Upregulation of the inducible isoform of HO-1 and increase its activity after treatment of animals with hemin 24 h before ischemia ameliorated myocardial function (raised left ventricular developed pressure, decreased end-di- astolic pressure, attenuated vasoconstriction) and reduced oxydative stress in cardiac tissue during reperfusion of iso- lated hearts. Zinc protoporphyrin IX, an inhibitor of heme oxygenase activity, completely abolished the HO-1 expres- sion in left ventricles of myocardium and increased postis- chemic myocardial dysfunction. Likewise, cardiac tissue in- jury was exacerbated by treatment with zinc protoporphyrin IX through significant inhibition of HO activity and increasing of hydroxyl radical production on reperfusion. The treatment of animals with hemin and following ischemia/reperfusion re- sulted in 5-6-times increase of HO-1 expression in the left ventricle of myocardium whereas in right ventricle only in 3- times. Our data provide strong evidence for a primary role of HO-1 in cardioprotection against reperfusion injury and show different HO-1 expression in left and right ventricles of myo- cardium.

References

  1. Кукоба Т.В., Мойбенко О.О., Коцюруба А.В. Кардіопротективна дія індукції гемоксигенази-1 за допомогою геміну при ішемії – реперфузії ізольо-ваного серця щура // Фізіол. журн. – 2003. – 49,№ 6. – C. 14–21.
  2. Amersi F., Buelow R., Kato H. et al. Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury // J. Clin. Invest. –1999. – 104. – P. 1631–1639.
  3. Benjamin I.J., McMillan D.R. Stress (heat shock) pro- teins: molecular chaperones in cardiovascular biology and disease // Circulat. Res. – 1998. – 27 (83), №2. –Р. 117–132.
  4. Black S.C., Lucchesi B.R. Heat shock proteins and the ischemic heart. An endogenous protective mechanism //Circulation. – 1993 – 87, №3. – Р. 1048–1051.
  5. Clark J.E., Foresti R., Sarathchandra P. et al. Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction // Amer. J. Physiol. – 2000. –278, Issue 2. – P. H643–H651.
  6. Csonka C., Varga E., Kovacs P. et al. Heme oxygenase and cardiac function in ischemic/reperfused rat hearts // Free Radic. Biol. Med. – 1999. – 27, №1–2. – P. – 119–126.
  7. Hangaishi M., Ishizaka N., Aizawa T. et al. Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo // Biochem. Biophys. Res. Commun. – 2000. – 20, (279), №2. – P. 582–588.
  8. Lee P.J., Alam J., Sylvester S.L. et al. Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury // Amer. J. Respir. Cell. Mol.Biol. – 1996. – 14, №6. – P. 556–568.
  9. 9. Maines MD. The geme oxygenase system: a regulator of second messenger gases // Annu Rev. Pharmacol.Toxicol. – 1997. – № 37. – P. 517–554.
  10. 10. Marber M.S., Mestril R., Chi S.H. et al. Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury // J. Clin. Invest. – 1995. – 95, №4. –Р. 1446–1456.
  11. Pataki T., Bak I., Csonka C. et al. Regulation of ven- tricular fibrillation by heme oxygenase in ischemic/reperfused hearts // Antioxid. Redox Signal. – 2001. –3, №1. – P. 125–134.
  12. Suttner D.M., Dennery P.A. Reversal of HO-1 related Т.В. Кукоба, А.В. Коцюруба, О.О. Мойбенко
  13. 84ISSN 0201-8489 Фізіол. журн., 2006, Т. 52, № 1 cytoprotection with increased expression is due to reactive iron // FASEB J. – 1999. – 13, № 13. –P. 1800–1809.
  14. Yamada N., Yamaya M., Okinaga S. et al. Protective Effects of Heme Oxygenase-1 against Oxidant-Induced Injury in the Cultured Human Tracheal Epithelium //Amer. J. Respir. Cell. Mol. Boil. – 1999. – 21, № 3. –P. 428–435.
  15. Yet S.F., Tian R., Layne M.D. et al. Cardiac-specific Вплив експресії та активності гемоксигенази-1 expression of heme oxygenase-1 protects against is-chemia and reperfusion injury in transgenic mice //Circulat. Res. – 2001. – 20 (89), №2. – P. 168–173.
  16. Yoshida T., Maulik N., Ho Y.S. et al. H (mox-1) constitutes an adaptive response to effect antioxidant cardioprotection: A study with transgenic mice het-erozygous for targeted disruption of the Heme oxyge-nase-1 gene // Circulation. – 2001. – 27 (103), №12. –P. – 1695–1701.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.