Spermine prevents endonuclease activation and apoptosis in thymocytes

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Abstract

Glucocorticoid hormones, Ca2+ ionophores, and some toxic chemicals activate a suicide process in thymocytes, known as apoptosis or programmed cell death. A crucial event in apoptosis is the activation of a Ca2+- and Mg2+-dependent endonuclease that promotes extensive DNA fragmentation. In this study, we investigated the effect of various polyamines on endonuclease activation leading to thymocyte apoptosis. We found that both glucocorticoid- and Ca2+ ionophore-induced DNA fragmentation and apoptosis were prevented by spermine. Other polyamines such as putrescine or spermidine had moderate or no effect. Moreover, spermine, and to a lesser extent spermidine, but not putrescine, prevented endonuclease activation in permeabilized liver nuclei incubated in the presence of Ca2+ and Mg2+, indicating that spermine efficiency in blocking DNA fragmentation was related to the interaction of this polyamine with the endonuclease or its substrate, DNA. Experiments with the fluorescent dye, ethidium bromide, and a purified preparation of liver endonuclease revealed that the protective effect of spermine on DNA fragmentation was related to its ability to modify the chromatin arrangement. Thymocytes incubated with methyl glyoxal bis(guanylhydrazone) to deplete intracellular spermine exhibited spontaneous DNA fragmentation, which suggests that modulation of the intracellular polyamine content and regulation of chromatin structure may play a critical role in the early phases of apoptosis. Finally, these results demonstrate that inhibition of DNA fragmentation also prevents the onset of apoptosis, directly linking endonuclease activation and cell death.

References (32)

  • D.J. McConkey et al.

    Arch. Biochem. Biophys

    (1989)
  • T.Y. Aw et al.

    Arch. Biochem. Biophys

    (1990)
  • D.P. Jones et al.

    J. Biol. Chem

    (1989)
  • D.J. McConkey et al.

    J. Biol. Chem

    (1989)
  • D.J. McConkey et al.

    J. Biol. Chem

    (1990)
  • E.W. Hafner et al.

    J. Biol. Chem

    (1979)
  • O. Heby et al.

    Trends Biol. Sci

    (1990)
  • C.W. Porter et al.
  • P. Pohjanpelto et al.

    J. Biol. Chem

    (1985)
  • F.G. Walz et al.

    J. Biol. Chem

    (1990)
  • D.R. Hewish et al.

    Biochim. Biophys. Res. Commun

    (1973)
  • P. Colson et al.

    FEBS Lett

    (1989)
  • L.J. Marton et al.
  • M. Perotti et al.

    FEBS Lett

    (1990)
  • M.J. Arends et al.

    Am. J. Pathol

    (1990)
  • A.H. Wyllie

    Nature

    (1980)
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    This study was supported by grants from the Swedish Medical Research Council (Proj. No. 03X-2471) and the Deutsche Forschung Gemeinschaft (to B. Brüne).

    1

    Present Address: Universität Konstanz. Fakultät für Biologie. Universitätsstrasse 10. Postfach 5560, D-7750 Konstanz. Germany.

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