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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. 2004; 50(5): 11-18


Autophagic and oncotic cardiomyocytes death in anoxia -reoxygenation

Tumanovska L.V., Dosenko V.E., Nagibin V.S., Makogon N.V., Moibenko A.A.

    A.A. Bogomoletz Institute of Physiology National Academy ofSciences of Ukraine, Kiev



Abstract

In experiments on isolated rat neonatal cardiomyocytes under anoxia-reoxygenation it was established the different types of cell death: non-programmed (oncotic) and programmed (apoptotic and autophagic). Propidium iodide and Hoechst 33342 staining revealed that alive, necrotic and apoptotic cell ratio after anoxia-reoxygenation was 77%, 14%, 9% respectively (86%, 9.6% and 4.4% in control). Electron microscopy of neonatal rat cardiomyocytes allows us to clarify the ultrastructural peculiarities of each type of cell death. Cytoplasm hydratation, swelling, cell membrane components vacuolization and sarcollemmal integrity alteration were typical for necrosis. The features of apoptosis include: cytoplasm osmiophylia, cell organelle destruction, chromatin condensation and nucleus fragmentation as well as blebs and apoptotic body formation. Autophagic cell death was characterized by the presence of large amount of different size vacuoles accompanied by significant cytoplasm osmiophylia, chromatin condensation or nucleus picnosis (nucleus fragmentation was not observed in these cells) and preservation of sarcollemmal integrity. The autophagic cardiomyocytes destruction was proved by specific monodansylcadaverine staining of vacuolar structures. We first showed the anoxia-reoxygenation-related autophagic cell death of neonatal rat cardiomyocytes. These results strongly suggest the necessity of autophagic cell death investigation in pathogenesis of cardiovascular diseases.

References

  1. Веремеенко К.Н., Досенко В.Е., Нагибин В.С. и др. Протеолитические ферменты и апоптоз // Укр. биохим. журн. – 2003. –75. – №6. – С.10–24.
  2. Мойбенко О.О., Юзьків М.Я., Тумановська Л.В., Коцюруба А.В. Гостра ішемія –реперфузія міо- карда: роль системи оксиду азоту // Фізіол. журн. – 2004. – 50, №2. – С.34–41.
  3. Семенов Д.Е. Лушникова Е.Л. Непомнящий Л.М. Особенности антрациклиновой модели кардио- миопатии: снижение синтеза белка, нарушение внутриклеточной регенерации и безнекротическая элиминация кардиомиоцитов // Бюл. эксперим. биологии и медицины, 2001. – 131, №5. – С.595–600.
  4. Akao M., Ohler A., O’Rourke B., Marban E. Mito- chondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells // Circulat. Res. – 2001. – 88, №12. – P.1267–1275.
  5. Aki T., Yamaguchi K., Fujimiya T., Mizukami Y. Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardio- myocyte-derived line H9c2 // Oncogene. – 2003. – 22, №52. – P.8529–8535.
  6. Bulteau A.-L., Lundberg K.C., Humphries K.M. et al. Oxidative modification and inactivation of the proteasome during coronary occlusion/reperfusion // J. Biol. Chem. – 2001. – 276, № 32. – P.30057–30063.
  7. Bursch W. The autophagosomal-lysosomal compart- ment in programmed cell death // Cell Death Differ. – 2001. – 8. – P.569–581.
  8. Hein S., Elsasser A., Kostin S. et al. Functional distur- bances due to structural remodeling in the failing human heart // Arch. Mal. Coeur. Vaiss. – 2002. – 95, №9. – P.815–820.
  9. 9. Kajstura J., Cheng W., Sarangarajan R. et al. Necrotic and apoptotic myocytes cell death in the aging heart of Fischer 344 rats // Amer. J. Physiol. – 1996 –271. – P.H1215–H1228.
  10. 10. Kitagawa H., Tani E., Ikemoto H. et al. Proteasome inhibitors induce mitochondria-independent apoptosis in human glioma cells // FEBS. Lett. – 1999. – 443, №2. – P.181–186.
  11. Klionsky D.J., Emr S.D. Autophagy as a regulated pathway of cellular degradation // Science. – 2000. – 290. – P.1717–1721.
  12. Kostin S., Pool L., Elsasser A. et al. Myocytes die by multiple mechanisms in failing human heart // Circulat. Res. – 2003. – 92, №7. – P.715–724.
  13. Marshansky V., Wang X., Bertrand R. et al. Proteaso- mes modulate balance among proapoptotic and antiapoptotic Bcl-2 family members and compromise functioning of the electron transport chain in leukemic cells // J. Immunol. – 2001. – 166, №5. – P.3130–3142.
  14. Munafo D.B., Colombo M.I. A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation // J. Cell Sci. – 2001. – 114. – P.3619–3629.
  15. Reinecke H., Zhang M., Bartosek T., Charles E.M. Survival, integration, and differentiation of cardio- myocyte grafts // Circulation. – 1999. – 100, №2. – P.193–202.
  16. Scarabelli T.M., Stephanou A., Pasini E. et al. Differ- ent signaling pathways induce apoptosis in endothe- lial cells and cardiac myocytes during ischemia/ reperfusion injury // Circulat. Res. – 2003. – 90. – P.745–748.
  17. Shimomura H., Terasaki F., Hayashi T. et al. Autoph- agic degeneration as a possible mechanism of myocar- dial cell death in dilated cardiomyopathy // Jаp. Circulat. J. – 2001. – 65. – P.965–968.
  18. Sperandio S., De Belle I., Bredesen D. An alternative, nonapoptotic form of programmed cell death // Proc. Natl. Acad. Sci. USA. – 2000. – 97, №26. – P.14376–14381.
  19. 19. Terman A., Dalen H., Eaton J.W. et al. Mitochondrial recycling and aging of cardiac myocytes: the role of autophagocytosis // Exp. Gerontol. – 2003. – 38, №8. – P.863–876.

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