Biochemistry (Moscow)

, Volume 67, Issue 7, pp 737–746 | Cite as

Effects of the Inhibitors of Dynamics of Cytoskeletal Structures on the Development of Apoptosis Induced by the Tumor Necrosis Factor

  • L. V. DomninaEmail author
  • O. Yu. Ivanova
  • B. V. Cherniak
  • V. P. Skulachev
  • J. M. Vasiliev


Changes in cytoskeletal structures have been investigated during apoptosis of epithelial HeLa cells induced by tumor necrosis factor-α (TNF-α). Shape and surface cell activity were investigated by time-lapse video microscopy, and changes of the cytoskeletal structure were studied by immune fluorescent microscopy. Addition of TNF-α to HeLa cell culture caused early disruption of the actin cytoskeleton and vinculin-containing focal contacts, keratin filaments, and microtubules. Rounding of cells, general blebbing, and nuclear fragmentation were observed at the terminal apoptotic stages. Actomyosin complex inhibitors, H7 and HA1077, suppressed blebbing (but not cell rounding) and activated the development of apoptosis. The latter suggests that in contrast to blebbing the general rounding does not depend on increased contractility of actomyosin cortex. These cytoskeletal inhibitors accelerated the development of apoptosis of HeLa cells and increased sensitivity of HeLa-Bcl-2 cells (transfected with DNA encoding antiapoptotic protein Bcl-2) to TNF-induced apoptosis. Damage of cytoskeletal structures significantly attenuated antiapoptotic activity of Bcl-2 in the HeLa-Bcl-2 cells. It is suggested that the stimulation of apoptosis by cytoskeletal inhibitors may be attributed to the altered distribution of cell organelles, especially, mitochondria.

TNF apoptosis actin cytoskeleton microtubules vinculin blebbing mitochondria 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kopnin, B. P. (2000) Biochemistry (Moscow), 65, 2-27.Google Scholar
  2. 2.
    Metcalfe, A., and Streuli, Ch. (1997) Bio Essays, 19, 711-720.Google Scholar
  3. 3.
    Mills, J. C., Stone, N. L., Erhardt, J., and Pittman, R. N. (1998) J. Cell Biol., 140, 627-636.Google Scholar
  4. 4.
    Pawlak, G., and Helfman, D. M. (2001) Curr. Opin. Genet. Devel., 11, 41-47.Google Scholar
  5. 5.
    Skulachev, V. P. (2001) Exp. Gerontol., 36, 995-1024.Google Scholar
  6. 6.
    Coleman, M. L., Sahai, E. A., Yeo, M., Bosch, M., Dewar, A., and Olson, M. F. (2001) Nature Cell Biol., 3, 339-345.Google Scholar
  7. 7.
    Leverrier, Y., and Ridley, A. J. (2001) Nature Cell Biol., 3, 91-93.Google Scholar
  8. 8.
    Sebbagh, M., Renvoilz, C., Hamelin, J., Riche, N., Bertoglio, J., and Breagd, J. (2001) Nature Cell Biol., 3, 346-352.Google Scholar
  9. 9.
    Chang, H. Y., and Yang, X. (2000) Microbiol. Mol. Biol. Rev., 821-846.Google Scholar
  10. 10.
    Reed, J. C. (1994) J. Cell Biol., 124, 1-6.Google Scholar
  11. 11.
    Reed, J. C. (1997) Nature, 387, 773-776.Google Scholar
  12. 12.
    Reed, J. C. (1997) Adv. Pharmacol., 41, 501-532.Google Scholar
  13. 13.
    Rovensky, Y. A., Domnina, L. V., Ivanova, O. Y., and Vasiliev, J. M. (1999) J. Cell Sci., 112, 1273-1282.Google Scholar
  14. 14.
    Sidoti-de Fraisse, C., Rincheval, V., Risler, Y., Mignotte, B., and Vayssiere, J.-L. (1998) Oncogene, 17, 1639-1651.Google Scholar
  15. 15.
    Seto, M., Sasaki, Y., and Hidaka, H. (1991) Eur. J. Pharmacol., 195, 267-272.Google Scholar
  16. 16.
    Cici, S. S., Volberg, T., Bershadsky, A. D., Denisenco, N., and Geiger, B. (1994) J. Cell Sci., 107, 683-692.Google Scholar
  17. 17.
    Guelshtein, V. I., Tchypisheva, T. A., Ermilova, V. D., Litvinova, L. V., Troyanovsky, S. M., and Bannikov, G. A. (1988) Int. J. Cancer, 42, 147-153.Google Scholar
  18. 18.
    Bratton, S. B., and Cohen, G. M. (2001) Trends Pharmacol. Sci., 22, 306-315.Google Scholar
  19. 19.
    Stegh, A. H., Herrmann, H., Lampel, S., Weisenberger, D., Andra, K., Seper, M., Wiche, G., Krammer, P. H., and Peter, M. E. (2000) Mol. Cell Biol., 20, 5665-5679.Google Scholar
  20. 20.
    Packard, B. Z., Komoriya, A., Brots, T. M., and Henkart, P. A. (2001) Immunology, 167, 5061-5066.Google Scholar
  21. 21.
    Rubtsova, S. N., Kondratov, R. V., Kopnin, P. B., Chumakov, P. M., and Vasiliev, J. M. (1998) FEBS Lett., 430, 353-357. Google Scholar
  22. 22.
    Volbracht, C., Leist, M., and Nicotera, P. (1999) Mol. Med., 5, 477-489. Google Scholar
  23. 23.
    Spector, I., Shochet, N. R., Kashman, Y., and Groweiss, A. (1983) Science, 219, 493-495.Google Scholar
  24. 24.
    Spector, I., Shochet, N. R., Blasberger, D., and Kashman,Y. (1989) Cell. Motil. Cytoskeleton, 13, 127-144.Google Scholar
  25. 25.
    Constantini, P., Jacotot, E., Decaudin, D., and Kroemer, G. (2000) Nat. Cancer Inst., 92, 1042-1053.Google Scholar
  26. 26.
    Radionov, V. I., Gyoeva, F. K., Tanaka, E., Bershadsky, A. D., Vasiliev, J. M., and Gelfand, I. M. (1993) J. Cell. Biol., 123, 1811-1820.Google Scholar
  27. 27.
    De Vos, K., Goossens, V., Boone, E., Vezcammen, D., Vancompernoll, K., Vendenabeele, P., Haegeman, G., Fiers, W., and Grooten, J. (1998) J. Biol. Chem., 273, 9673-9680.Google Scholar
  28. 28.
    De Vos, K., Severin, F., van Herrewoghe, F., Gossens, V., Hyman, A., and Grooten, J. (2000) J. Cell Biol., 149, 1207-1214.Google Scholar

Copyright information

© MAIK “Nauka/Interperiodica” 2002

Authors and Affiliations

  • L. V. Domnina
    • 1
    Email author
  • O. Yu. Ivanova
    • 1
  • B. V. Cherniak
    • 1
  • V. P. Skulachev
    • 1
  • J. M. Vasiliev
    • 1
  1. 1.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia

Personalised recommendations