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Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes

Abstract

Cell surface 'blebbing' is an early consequence of hypoxic and toxic injury to cells1–5. A rise in cytosolic free Ca2+ has been suggested as the stimulus for bleb formation3–5 and the final common pathway to irreversible cell injury6–9. Here, using digitized low-light video microscopy, we examine blebbing, cytosolic free Ca2+, mitochondrial membrane potential and loss of cell viability in individual cultured hepatocytes. Unexpectedly, we found that after 'chemical hypoxia' with cyanide and iodoacetate, cytosolic free Ca2+ does not change during bleb formation or before loss of cellular viability. Cell death was precipitated by a sudden breakdown of the plasma membrane permeability barrier, possibly caused by rupture of a cell surface bleb.

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References

  1. Trump, B. F., Pentilla, A. & Berezesky, I. K. Virchows Arch. B Cell Path. 29, 281–307 (1979).

    CAS  Google Scholar 

  2. Lemasters, J.J., Ji, S. & Thurman, R. G. Science 213, 661–663 (1981).

    Article  ADS  CAS  Google Scholar 

  3. Jewell, S. A., Bellomo, G., Thor, H. & Orrenius, S. Science 217, 1257–1259 (1982).

    Article  ADS  CAS  Google Scholar 

  4. Lemasters, J. J., Stemkowski, C. J., Ji, S. & Thurman, R. G. J. Cell Biol. 97, 778–786 (1983).

    Article  CAS  Google Scholar 

  5. Thor, H., Hartzell, P. & Orrenius, S. J. biol. Chem. 259, 6612–6615 (1985).

    Google Scholar 

  6. Schanne, F. A. X., Kane, A. B., Young, E. E. & Farber, J. L. Science 206, 700–702 (1979).

    Article  ADS  CAS  Google Scholar 

  7. Trump, B. F. et al. in Scanning Electron Microscopy (ed. A. M. F. O'Hare) 437–462 (SEM Inc., Chicago, 1980).

    Google Scholar 

  8. Farber, J. L., Lab. Invest. 47, 114–123 (1982).

    CAS  PubMed  Google Scholar 

  9. Bellomo, G. & Orrenius, S. Hepatology 5, 876–882 (1985).

    Article  CAS  Google Scholar 

  10. Hochachka, P. W. Science 231, 234–241 (1986).

    Article  ADS  CAS  Google Scholar 

  11. Grynkiewicz, G., Poenie, M. & Tsien, R. Y. J. biol. Chem. 260, 3440–3450 (1985).

    CAS  PubMed  Google Scholar 

  12. Williams, D. A., Fogarty, K. E., Tsien, R. Y. & Fay, F. S. Nature 318, 558–561 (1985).

    Article  ADS  CAS  Google Scholar 

  13. Johnson, L. V., Walsh, M. L., Bockus, B. J. & Chen, L. B. J. Cell Biol. 88, 526–535 (1981).

    Article  CAS  Google Scholar 

  14. Krishan, A. J. Cell Biol. 66, 188–193 (1975).

    Article  CAS  Google Scholar 

  15. DiGuiseppi, J., Inman, R., Ishihara, A., Jacobson, K. & Herman, B. BioTechniques 3, 394–403 (1985).

    Google Scholar 

  16. Charest, R., Blackmore, P. F., Berthon, B. & Exton, J. H. J. biol. Chem. 258, 8769–8773 (1983).

    CAS  PubMed  Google Scholar 

  17. Binet, A., Bertho, B. & Claret, M. Biochem. J. 228, 565–574 (1985).

    Article  CAS  Google Scholar 

  18. Morris, J. D. H., Metcalfe, J. C., Smith, G. A., Hesketh, T. R. & Taylor, M. V. FEBS Lett. 169, 189–193 (1984).

    Article  CAS  Google Scholar 

  19. Moolenaar, W. H., Aerts, R. J., Tertoolen, L. G. J. & de Laat, S. W. J. biol. Chem. 261, 279–284 (1986).

    CAS  PubMed  Google Scholar 

  20. Cobbold, P. H. & Bourne, P. K. Nature 312, 444–446 (1984).

    Article  ADS  CAS  Google Scholar 

  21. Cobbold, P. H., Bourne, P. K. & Cuthbertson, K. S. R. Basic Res. Cardiol. 80, (Suppl. 2), 155–158 (1985).

    PubMed  Google Scholar 

  22. Allen, D. G. & Orchard, C. H. J. Physiol. 339, 107–122 (1983).

    Article  CAS  Google Scholar 

  23. Allen, D. G. & Orchard, C. H. J. molec. Cell Cardiol. 16, 117–128 (1984).

    Article  CAS  Google Scholar 

  24. Borle, A. B. & Snowdowne, K. W. Science 217, 252–254 (1982).

    Article  ADS  CAS  Google Scholar 

  25. Snowdowne, K. W., Freudenrich, C. C. & Borle, A. B. J. biol. Chem. 260, 11619–11626 (1985).

    CAS  PubMed  Google Scholar 

  26. Bradford, B. U., Marotto, M., Lemasters, J. J. & Thurman, R. G. J. Pharmac. exp. Ther. 236, 263–268 (1986).

    CAS  Google Scholar 

  27. Alberts, B. et al. Molecular Biology of the Cell (Garland, New York, 1983).

    Google Scholar 

  28. Emaus, R. K., Grunwald, R. & Lemasters, J. J. Biochim. biophys. Acta 850, 436–448 (1986).

    Article  CAS  Google Scholar 

  29. Hoek, J. B., Nicholls, D. G. & Williamson, J. R. J. biol. Chem. 255, 1458–1464 (1980).

    CAS  PubMed  Google Scholar 

  30. Andersson, B. S. & Jones, D. P. Analyt. Biochem. 146, 164–172 (1985).

    Article  CAS  Google Scholar 

  31. Veech, R. L., Lawson, J. W. R., Cornell, N. W. & Krebs, H. A. J. biol. Chem. 254, 6538–6547 (1979).

    CAS  PubMed  Google Scholar 

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Lemasters, J., DiGuiseppi, J., Nieminen, AL. et al. Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes . Nature 325, 78–81 (1987). https://doi.org/10.1038/325078a0

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