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. 2013; 59(3): 3-9

Influence of flocalin on development of apoptosis and necrosis at anoxia-reoxygenation of culture rats neonatal cardiomyocytes

Strutyns'kyĭ RB, Nagibin VS, Strutyns'ka NA, Ianchiĭ OR, Moĭbenko OO

    Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz59.03.003


Abstract

The influence of the new cardioprotector flocalin was investigated on the culture of rat's neonatal cardiomyocytes during anoxia-reoxygenation modelling. The mechanisms of apoptosis and necrosis were investigated under influence of ATP-sensitive potassium (K(ATP)) channels activation and in conditions of blocking of the L-type calcium (VGCCs) channels. Flocalin was added in the culture medium in the dose 5 and 20 microM at 2 minutes before anoxia (30 minutes) and following reoxygenation (60 minutes). These doses are near to: the first dose means the opening of K(ATP) channels and the second one means the IC50 block of VGCCs. It is discovered that in dose 5 microM of flocalin drew the change of correlation of living, necrotizing and apoptizing cells drew side-shifting living. The number of live cells was almost the same like in control (experiments without anoxia-reoxygenation modelling). The opening of K(ATP) channels decreases necrosis in two times and fully prevented development of apoptosis which was induced anoxia-reoxygenation modelling. Flocalin depressed the apoptosis of neonatal cardiomyocytes so that he was on to 36% less than in control group (without anoxia-reoxygenation). But in the high dose (20 microM) that provokes not only K(ATP) channels opening but also IC50 block of VGCCs cardioprotection was not detected after modelling of anoxia-reoxygenation. The last can be investigation both enough strong activating of the potassium channels and by investigation of both factors are opening of potassium and inhibition of VGCCs channels and, accordingly, substantial diminishing of level of introcellular Ca2+ and violation of metabolic processes yet to anoxia-reoxygenation. Thus, small doses of flocalin, that induce moderate opening of K(ATP) channels significantly decrease the number of necrotic and apoptotic cells in culture of rat neonatal cardiomyocytes induced by anoxia-reoxygenation.

Keywords: ATP-sensitive potassium channels, apoptosis,necrosis, anoxia-reoxygenation, rat neonatal cardiomyocytes,flocalin.

Full text: (PDF, in Ukrainian)

References

  1. Moibenko O.O., strutins'kii R.B., Yagupol's'kii L.M., Mohort M.A., Shalamai A.s. Organizatsiya za-vods'kogo vigotovlennya preparatu Flokalin novogo vitchiznyanogo miotropnogo spazmolitika i kardioprotek-tora . Nauka ta innovatsii. 2009. 5, N 1. p.80-84.
    2.  
  2. Nagibin V.s., Dosenko V.Ie., pivovar s.M., Moibenko O.O., Yagupol's'kii L.M. Ftorovanii analog diazok-sidu poperedzhaie apoptoz neonatal'nih kardiomiotsitiv pid chas anoksii-reoksigenatsii . Fiziol. zhurn. 2004. 50, N 3. p.3-8.
    3.  
  3. Strutins'kii R.B., Kotsyuruba A.V., Neshcheret O.p., Rovenets' R.A., Moibenko O.O. Zmini metabolizmu v miokardi pri ishemii-reperfuzii ta aktivatsii adenozin-trifosfatchutlivih kaliievih kaliievih kanaliv . Tam samo. 2012. 58, N 1. p.13-26.
    4.  
  4. Strutins'kii R.B., Kotsyuruba A.V., Neshcheret O.p., Shish A.M., Rovenets' R.A., Moibenko O.O. Kardiopro-tektorni efekti aktivatsii adenozintrifosfatzalezh-nih kaliievih kanaliv v eksperimentah in vivo: vpliv na biohimichni parametri krovi za umov ishemii-reperfuzii miokarda . Tam samo. 2009. 55, N 6. p.12-19.
    5.  
  5. Strutins'kii R.B., Moibenko O.O., Chebanov V. A., Gorobets' M. Yu. Modelyuvannya promislovogo protsesu virobnitstva preparatu "Flokalin" ta viznachennya iogo optimal'no-efektivnoi dozi dlya likuvannya zahvoryuvan' sertsya . Nauka ta innovatsii. 2013. 9, N 1. p.55-63.
    6.  
  6. Strutins'kii R., Mohort M., Yagupol's'kii L., Moibenko O. Flokalin novii vitchiznyanii kardioprotek-tor . Visn. farmakologii ta farmatsii. 2010. N 3. p.44-56.
    7.  
  7. Strutins'kii R.B., pivovar s.M., Tumanovs'ka L.V., Moibenko O.O. Kardioprotektorni efekti flokalinu: vidnosna rol' aktivatsii sarkolemal'nih ta mitohon-drial'nih adenozintrifosfatzalezhnih kaliievih kanaliv . Fiziol.zhurn. 2008. 54, N 6. p.15-23.
    8.  
  8. Strutins'kii R.B., Frantsuzova s.B., Rovenets' R.A., Tumanovs'ka L.V., Moibenko O.O. Flokalin novii vitchiznyanii kardioprotektor . patologiya. 2008. 5, N 3. p.22.
    9.  
  9. Alizadeh A.M., Faghihi M., Khori V., Sohanaki H., Pourkhalili K., Mohammadghasemi F., Mohsenikia M.Oxytocin protects cardiomyocytes from apoptosis induced by ischemia-reperfusion in rat heart: role of mitochondrial ATP-dependent potassium channel and permeability transition pore . Peptides. 2012. 36, N 1. p. 71-77. CrossRef PubMed
    10.  
  10. Bourgine A., Beck L., Khoshniat S., Wauquier F., Oliver L., Hue E., Alliot-Licht B., Weiss P., Guicheux J., Wittrant Y. Inorganic phosphate stimulates apoptosis in murine MO6-G3 odontoblast-like cells . Arch Oral Biol. 2011. 56, N 10. p. 977-983. CrossRef PubMed
    11.  
  11. Brouard S., Berberat P.O., Tobiasch E., Seldon M.P., Bach F.H., Soares M.P. Heme oxygenase-1-derived carbon requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis . J. Biol. Chem. 2002. 277, N 20. P.17950-17961. CrossRef PubMed
    12.  
  12. Coito A.J., Buelow R., Shen X.D., Amersi F., Moore C., Volk H.D., Busuttil R.W., Kupiec-Weglinski J.W. Heme oxygenase-1 gene transfer inhibits inducible nitric oxide synthase expression and protects genetically fat Zucker rat livers from ischemia-reperfusion injury . Transplantation. 2002. 74, N 1. p. 96-102. CrossRef PubMed
    13.  
  13. Das A., Xi L., Kukreja R.C. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling . J. Biol. Chem. 2005. 280, N 13. p. 12944-12955. CrossRef PubMed
    14.  
  14. Flagg T.P., Nichols C.G. Sarcolemmal KATP channels: what do we really know? . J. Mol. and Cell Cardiol. 2005. 39. P.61-70. CrossRef PubMed
    15.  
  15. Halestrap A.P., Clarke S.J., Javadov S.A. Mitochondrial permeability transition pore opening during myocardial reperfusion a target for cardioprotection . Cardiovascular Res. 2004. 61, N 3. p.372-385. CrossRef  
  16. Li P.F., Dietz R., von Harsdorf R. Differential effect of hydrogen peroxide and superoxide anion on apoptosis and proliferation of vascular smooth muscle cells . Circulation. 1997. 96, N 10. p.3602-3609. CrossRef PubMed
    17.  
  17. Liu D., Lu C., Wan R., Auyeung W.W., Mattson M.P. Activation of mitochondrial ATP-dependent potassium channels protects neurons against ischemia-induced death by a mechanism involving suppression of Bax transloca-tion and cytochrome c release . J. Cereb. Blood. Flow. Metab. 2002. 22, N 4. p.431-443. CrossRef PubMed
    18.  
  18. Mansceld K., Pucci B., Adams C.S., Shapiro I.M. Induction of apoptosis in skeletal tissues: phosphate-mediated chick chondrocyte apoptosis is calcium dependent . Calcif Tissue Int. 2003. 73, N 2. p.161-172. CrossRef PubMed
    19.  
  19. Patten R.D., Denofrio D., El-Zaru M., Kakkar R., Saunders J., Celestin F., Warner K., Rastegar H., Khabbaz K.R., Udelson J.E., Konstam M.A., Karas R.H. Ventricular assist device therapy normalizes inducible nitric oxide expression and reduces cardiomyocyte apoptosis in the failing human heart . J. Amar Coll Cardiol. 2005. 45, N 9. P.1419-1424. CrossRef PubMed
    20.  
  20. Ramasamy R., Hwang Y.C., Liu Y., Son N.H., Ma N., Parkinson J., Sciacca R., Albala A., Edwards N., Szabolcs M.J., Cannon P.J. Metabolic and functional protection by selective inhibition of nitric oxide synthase 2 during ischemia-reperfusion in isolated perfused hearts . Circulation. 2004. 109, N 13. P.1668-1673. CrossRef PubMed
    21.  
  21. Reinecke H., Zhang M., Bartosek., Charles E.M. Survival, integration and differentiation of cardiomyocyte grafts . Circulation. 1999. 100, N 2. P.193-202. CrossRef PubMed
    22.  
  22. Voitychuk O.I., Strutynskyi R.B., Moibenko O.O., Shuba Y.M. Effects of ?uorine-containing opener of ATP-sensitive potassium channels, pinacidil-derivative ?ocalin, on cardiac voltage-gated sodium and calcium channels . NSAP. 2012. 385, N 11. p.1095-1102. CrossRef PubMed
    23.  
  23. Voitychuk O.I., Strutynskyi R.B., Yagupolskii L.M., Tinker Moibenko O.O., Shuba Y.M. Sarcolemmal cardiac KATP channels as a target for the cardioprotective effects of the ?uorine-containing pinacidil analogue ?ocalin . Brit. J. Pharmacol. 2011. 162, N 3. p.701-711. CrossRef PubMed PubMedCentral
    24.  
  24. Yagami T., Yamamoto Y., Kohma H., Nakamura T., Takasu N., Okamura N. L-type voltage-dependent calcium channel is involved in the snake venom group IA secretory phospholipase A2-induced neuronal apoptosis . Neurotoxicology. 2013. 35. p.146-153. CrossRef PubMed
    25.  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.