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. 2008; 54(3): 10-21


Ultrastructural changes inisolated cardiomyocytes in modeling of endoplasmic reticulum stress

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

    O.O.Bogomoletz Institute of Physiology National Academy ofSciences of Ukraine Kiyv


Abstract

At modeling of endoplasmatic reticulum (ER) stress by it classic inducer thapsigargin, anoxia-reoxygenation and simul- taneous inhibition of proteasomal proteolysis, autophagy and apoptosis a diversity of ultrastructural peculiarities was shown. Their comparison allows to make a conclusion that changes in these groups of experiments are similar and typical for ER stress. Thapsigargin application was shown to result in accu- mulation of giant mitochondria in perinuclear zone of cardi- omyocytes. Some of these mitochondria had destroyed and high condensed matrix. The structure of ER was normal but in some regions of cells the dilation of ER cisterns occurred that, to our opinion, is an essential sign of ER stress. In another group of cells thapsigargin caused dehydratation and osmiophilia of cytoplasm, significant dilation of ER cisterns, partial or complete degranulation of these organelles that often formed vacuoles with high electron density material. Also, the significant decrease of the number and size of mitochondria that had partially destroyed and condensed matrix was ob- served in these cells. The accumulation of lipofuscin and myophilament destruction at preservation of sarcoplasmic membrane integrity was detected. However, in conditions of simultaneous inhibition of proteasomal proteolysis, aytophagy and apoptosis the loss of membrane integrity was shown, and we propose that it unconditionally should cause necrotic cell death. That was confirmed by use of fluorogenic dyes to de- tect necrosis and apoptosis. Our data indicate the important role of ER stress in processes of cardiomyocytes death at anoxia-reoxygenation and inhibition of proteasomal and au- tophagic proteolysis.

References

  1. Тумановська Л.В., Досенко В.Є., Нагібін В.С. та ін. Апоптотична, аутофагічна та онкотична загибель кардіоміоцитів при аноксії-реоксигенації // Фізіол.журн. – 2004. – 50, №5. – С.11–18.
  2. Baumeister P., Luo S., Skarnes W.C. et al. Endoplas- mic reticulum stress induction of the grp78/bip pro-moter: activating mechanisms mediated by YY1 andits interactive chromatin modifiers // Mol. and Cell. Biol. – 2005. – 25, №11. – P. 4529–4540.
  3. Bausero M.A., Gastpar R., Multhoff G., Asea A. Al-ternative mechanism by which IFN-? enhances tumor recognition: active release of heat shock protein 72 // J.Immunol. – 2005. – 175, №5. – P. 2900–2912.
  4. Boelens J., Lust S., Offner F. et al. The endoplasmic reticulum: a target for new anticancer drugs // In Vivo. – 2007. – 21, №2. – P.215–226.
  5. Fribley A., Zeng Q., Wang C. Proteasome inhibitor PS- 341 induces apoptosis through induction of endoplas- mic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells // Mol. and Cell. Biol. – 2004. – 24, №22. – P.9695–9704.
  6. Fujita1 E., Kouroku1 Y., Isoai A. et al. Two endoplasmic reticulum-associated degradation (ERAD) systems for the novel variant of the mutant dysferlin: ubiquitin/ proteasome ERAD(I) and autophagy/lysosome ERAD(II) // Human Mol. Genetics. – 2007. – 16, №6. –P.618–629.
  7. Glickman M.H., Ciechanover A. The ubiquitinproteasome proteolytic pathway:destruction for the sake of construction // Physiol. Rev. – 2002. – 82. – P.373–428.
  8. Jiang H., Wek R.C. Phosphorylation of the ?-subunit of the eukaryotic initiation factor-2 (eIF2 ? ) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition // J. Biol. Chem. – 2005. – 280,№14. – P. 14189–14202.
  9. 9. Kim R., Emi M., Tanabe K., Murakami S. Role of the unfolded protein response in cell death // Apoptosis. –2006. – 11, №1. – P.5–13.
  10. 10. Lai E, Teodoro T, Volchuk A. Endoplasmic reticulum stress: signaling the unfolded protein response // Physiology (Bethesda). – 2007. – 22, № 3. – P.193–201.
  11. Lee G.H., Kim H.K., Chae S.W. et al. Bax inhibitor-1 regulates endoplasmic reticulum stress-associated reactive oxygen species and heme oxygenase-I expression // J. Biol.Chem. – 2007. – 282, №30. – P.21618–21628.
  12. Marciniak S.J., Yun C.Y., Oyadomari S. et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum // GenesDev. – 2004. – 18, №24. – P.3066–3077.
  13. Morishima N., Nakanishi K., Takenouchi H. et al. An endoplasmic reticulum stress-specific caspase cascade in apoptosis cytochrome c-independent activation of caspase-9 by caspase-12 // J. Biol. Chem. – 2002. –277, №37. – P.34287–34294.
  14. Mulugeta S., Nguyen V., Russo S.J. et al. A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation // Amer. J. Respir. Cell. Mol. Biol. – 2005. – 32, № 6. – P.521–530.
  15. Nickson P., Toth A., Erhardt P. PUMA is critical for neonatal cardiomyocyte apoptosis induced by endoplasmic reticulum stress // Cardiovascular. Res. – 2007. –73, № 1. – P.48–56.
  16. Obeng E.A., Boise L.H. Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis // J. Biol. Chem. – 2005. – 280, №33. – P.29578–29587.
  17. Oyadomari S., Yun C., Fisher E.A. Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload // Cell. – 2006. – 126, №4. – P.727–739.
  18. Rao R.V., Hermel E., Castro-Obregon S. et al. Coupling endoplasmic reticulum stress to the cell death program mechanism of caspase activation // J. Biol. Chem. –2001. – 276, № 36. – P.33869–33874.
  19. 19. Rutishauser J., Spiess M. Endoplasmic reticulum stor- age diseases // Swiss. Med. Wkly. – 2002. – 132, №17 – 18. – P.211–222.
  20. 20. Szegezdia E., Duffyc A., Martin E. et al. ER stress contributes to ischemia-induced cardiomyocyte apoptosis // Biochem. and Biophys. Res. Commun. –2006. – 349, №4. – P.1406–1411.
  21. Dosenko V.E., Nagibin V.S., Tumanovska L.V., Moibenko A.A. Protective effect of autophagy in anoxia-reoxygenation of isolated cardiomyocyte? // Autophagy. – 2006. – 2, №4. – P.305–306.
  22. Dosenko V.E., Nagibin V.S., Tumanovskaya L.V. et al. Proteasomal proteolysis in anoxia-reoxygenation, preconditioning and postconditioning of isolated cardiomyocytes// Pathophysiology. – 2006. – 13, №2. – P.119–125.
  23. Nagibin V.S., Dosenko V.E., Moibenko A.A. Proteasomal activity in isolated neonatal cardiomyocytes in anoxia-reoxygenation // Abstracts of Joint 59th Harden EMBO Conf. “The ubiquitin proteasome system in health and disease” (Cirencester, 6–10 Sept., 2004). –Cirencester, 2004. – P.13.
  24. Nagibin V.S, Dosenko V.E. Tumanovskaya L.V., Moibenko O.O. Apoptotic and autophagic death of cardiomyocytes in anoxia–reoxygenation and at inhibition of proteasome activity // Abstracts of 12th Euroconference on apoptosis (Chania, 17–20 Sept. 2004). – Chania, 2004. – P.117.
  25. Reinecke H., Zhang M., Bartosek T., Charles E.M. Sur- vival, integration, and differentiation of cardiomyocyte grafts // Circulation. – 1999. – 100. – P.193 – 202.
  26. Delisle B.P., Anderson C.L., Balijepalli R.C. et al. Thapsigargin selectively rescues the trafficking defective LQT2 channels G601S and F805C // J. Biol. Chem. –2003. – 278, №37. – P.35749–35754.
  27. Munafo D.B., Colombo M.I. A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation // J. Cell Science. – 2001. –114. – P.3619–3629

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