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Role of Intracellular pH in Proliferation, Transformation, and Apoptosis

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Abstract

Both cellular proliferation and apoptosis (programmed cell death) have been claimed to be modulated, perhaps even triggered by, changes in intracellular pH. In this review, we summarize the evidence that gave rise to these hypotheses. To facilitate a critical appraisal of the existing data, we briefly review the main pathways involved in cytosolic pH homeostasis and their regulation by mitogens and by apoptosis-inducing agents. The information available at present suggests that cytosolic pH plays a permissive role in cellular growth and proliferation, but is neither a trigger nor an essential step in the mitogenic signal transduction cascade. Concerning apoptosis, it is clear that lowering the pH in vitro can activate DNase II. However, the evidence linking cytosolic acidification with DNA degradation in vivois presently not convincing. We conclude that the cytosolic pH, an essential physiological parameter that is tightly controlled by multiple, complementary, or redundant systems, is unlikely to play a role in signalling either cell growth or death.

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REFERENCES

  • Barbiero, G., Duranti, F., Bonelli, G., Amenta, J. S., and Baccino, F. M. (1995). Exp. Cell Res. 217, 410–418.

    Google Scholar 

  • Barry, M. A., and Eastman, A. (1992). Biochem. Biophys. Res. Commun. 186, 782–789.

    Google Scholar 

  • Barry, M. A., Reynolds, J. E., and Eastman, A. (1993). Cancer Res. 53, 2349–2357.

    Google Scholar 

  • Bussolino, F., Wang, J. M., Turrini, F., Alessi, D., Ghino, D., Costamagna, C., Pescarmona, G., Mantovani, A., and Bosia, A. (1989). J. Biol. Chem. 264, 18284–18287.

    Google Scholar 

  • Caceres-Cortes, J., Rajotte, D., Dumouchel, J., Haddad, P., and Hoang, T. (1994). J. Biol. Chem. 269, 12084–12091.

    Google Scholar 

  • Doppler, W., Jaggi, R., and Groner, B. (1987). Gene 54, 147–153.

    Google Scholar 

  • Durand, R. E. (1991). Int. J. Radiat. Oncol. Biol. Phys. 20, 253–258.

    Google Scholar 

  • Eastman, A., and Barry, M. A. (1992). Cancer Invest. 10, 229–240.

    Google Scholar 

  • Ellis, H. M., and Horvitz, H. R. (1986). Cell 44, 817–829.

    Google Scholar 

  • Forgac, M. (1989). Physiol. Rev. 69, 765–796.

    Google Scholar 

  • Furuya, Y., Lundmo, P., Short, A. D., Gill, D. L., and Isaacs, J. T. (1994). Cancer Res. 54, 6167–6175.

    Google Scholar 

  • Ganz, M. B., Boyarsky, G., Sterzel, R. B., and Boron, W. F. (1989). Nature 337, 648–651.

    Google Scholar 

  • Goldstein, D. J., Finbow, M. E., Andresson, T., McLean, P., Smith, K., Bubb,.V, and Schlegel, R. (1991). Nature 352, 347–349.

    Google Scholar 

  • Goss, G. G., Woodside, M., Wakabayashi, S., Pouyssegur, J., Waddell, T., Downey, G. P., and Grinstein, S. (1994). J. Biol. Chem. 269, 8741–8748.

    Google Scholar 

  • Gottlieb, R. A., Nordberg, J., Skowronski, E., and Babior, B. M. (1996). Proc. Natl. Acad. Sci. USA 93, 654–658.

    Google Scholar 

  • Griffiths, J. R. (1991). Br. J. Cancer 64, 425–427.

    Google Scholar 

  • Grinstein, S., Rotin, D., and Mason, M. J. (1989). Biochim. Biophys. Acta 988, 73–97.

    Google Scholar 

  • Gunn, J. M., Martinez-Zaguilan, R., Wald-Hopkins, S., Woolridge, D., and Gillies, R. J. (1994). Arch. Biochem. Biophys. 314, 268–275.

    Google Scholar 

  • Hagag, N., Lacal, J. C., Graber, M., Aaronson, S., and Viola, M. V. (1987). Mol. Cell. Biol. 7, 1984–1988.

    Google Scholar 

  • Harguindey, S., and Cragoe, E. J. Jr. (1992). Med. Hypotheses 39, 229–237.

    Google Scholar 

  • Hooley, R., Yu, C.-Y., Symons, M., and Barber, D. L. (1996). J. Biol. Chem. 271, 6152–6158.

    Google Scholar 

  • Kaplan, D. L., and Boron, W. F. (1994). J. Biol. Chem. 269, 4116–4124.

    Google Scholar 

  • Kapus, A., Grinstein, S., Wasan, S., Kandasamy, R., and Orlowski, J. (1994). J. Biol. Chem. 269, 23544–23552.

    Google Scholar 

  • L'Allemain, G., Paris, S., and Pouyssegur, J. (1984). J. Biol. Chem. 259, 5809–5815.

    Google Scholar 

  • Lev, S., Yarden, Y., and Givol, D. (1992). J. Biol. Chem. 267, 15970–15977.

    Google Scholar 

  • Li, J., and Eastman, A. (1995). J. Biol. Chem. 270, 3203–3211.

    Google Scholar 

  • Lin, X., Voyno-Yasenetskaya, T. A., Hooley, R., Lin, C.-Y., Orlowski, J., and Barber, D. L. (1996). J. Biol. Chem. 271, 22604–22610.

    Google Scholar 

  • Martinez-Zaguilan, R., Lynch, R. M., Martinez, G. M., and Gillies, R. J. (1993). Am. J. Physiol. 265, C1015–C1029.

    Google Scholar 

  • McSwine, R. L., Li, J., and Villereal, M. L. (1996). J. Cell. Physiol. 168, 8–17.

    Google Scholar 

  • Meisenholder, G. W., Martin, S. J., Green, D. R., Nordberg, J., Babior, B. M., and Gottlieb, R. A. (1996). J. Biol. Chem. 271, 16260–16262.

    Google Scholar 

  • Newell, K., Franchi, A., Pouyssegur, J., and Tannock, I. (1993). Proc. Natl. Acad. Sci. USA 90, 1127–1131.

    Google Scholar 

  • Ng, L. L., and Davies, J. E. (1991). Am. J. Physiol. 261, C780–C786.

    Google Scholar 

  • Nobes, C. D., and Hall, A. (1995). Cell 81, 53–62.

    Google Scholar 

  • Perez-Sala, D., Collado-Escobar, D., and Mollinedo, R. (1995). J. Biol. Chem. 270, 6235–6242.

    Google Scholar 

  • Perona, R., and Serrano, R. (1988). Nature 334, 438–440.

    Google Scholar 

  • Rajotte, D., Haddad, P., Haman, A., Cragoe, Jr., E. J., and Hoang, T. (1992). J. Biol. Chem. 267, 9980–9987.

    Google Scholar 

  • Rebollo, A., Gomez, J., Martinez de Aragon, A., Lastres, P., Silva, A., and Perez-Sala, D. (1995). Exp. Cell Res. 218, 581–585.

    Google Scholar 

  • Reynolds, J. E., Li, J., Craig, R. W., and Eastman, A. (1996). Exp. Cell Res. 225, 430–436.

    Google Scholar 

  • Rockwell, S., and Hughes, C. S. (1990). In Effects of Therapy on Biology and Kinetics of the Residual Tumor, Part B: Clinical Aspects (Ragaz, J., Simpson-Herren, L., and Fisher, B., eds.), Wiley-Liss, New York, pp. 67–80.

    Google Scholar 

  • Schwartz, E. L., Chamberlin, H., and Brechbuhl, A.-B. (1991). Blood 77, 2716–2723.

    Google Scholar 

  • Stahl, N., and Yancopoulos, G. D. (1993). Cell 74, 587–589.

    Google Scholar 

  • Stubbs, M., Veech, R. L., and Griffiths, J. R. (1995). Adv. Enzyme Regul. 35, 101–115.

    Google Scholar 

  • Tsao, N., and Lei, H.-Y. (1996). J. Immunol. 157, 1107–1116.

    Google Scholar 

  • Vallance, S. J., Downes, C. P., Cragoe, Jr., E. J., and Whetton, A. D. (1990). Biochem. J. 265, 359–364.

    Google Scholar 

  • Vexler, Z. S., Symons, M., and Barber, D. L. (1996). J. Biol. Chem. 271, 22281–22284.

    Google Scholar 

  • Wakabayashi, S., Shigekawa, M., and Pouyssegur, J. (1997). Physiol. Rev. 77, 51–74.

    Google Scholar 

  • Weinberg, J. M., Davis, J. A., Roeser, N. F., and Venkatachalam, M. A. (1994). J. Am. Soc. Nephrol. 5, 1314–1323.

    Google Scholar 

  • Wyllie, A. H., Arends, M. J., Morris, R. G., Walker, S. W., and Evan, G. (1992). Semin. Immunol. 4, 389–397.

    Google Scholar 

  • Zhu, W.-H., and Loh, T.-T. (1995). Biochim. Biophys. Acta 1269, 122–128.

    Google Scholar 

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Authors and Affiliations

  1. Division of Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada

    Lamara D. Shrode, Hans Tapper & Sergio Grinstein

  2. Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

    Sergio Grinstein

  3. Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, Lund, Sweden

    Hans Tapper

Authors
  1. Lamara D. Shrode
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  2. Hans Tapper
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  3. Sergio Grinstein
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Shrode, L.D., Tapper, H. & Grinstein, S. Role of Intracellular pH in Proliferation, Transformation, and Apoptosis. J Bioenerg Biomembr 29, 393–399 (1997). https://doi.org/10.1023/A:1022407116339

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