Involvement of p53 in DNA Strand Break-induced Apoptosis in Postmitotic CNS Neurons

Authors

  • Yasushi Enokido,

    Corresponding author
    1. Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, 3–2 Yamadaoka, Suita, Osaka 565, Japan
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  • Toshiyuki Araki,

    1. Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, 3–2 Yamadaoka, Suita, Osaka 565, Japan
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  • Kiyoji Tanaka,

    1. Division of Cellular Genetics, Institute for Molecular and Cellular Biology, Osaka University, 1–3 Yamadaoka, Suita, Osaka 565, Japan
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  • Shinichi Aizawa,

    1. Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, 2-2-1 Honjyo, Kumamoto, Kumamoto 860, Japan
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  • Hiroshi Hatanaka

    1. Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, 3–2 Yamadaoka, Suita, Osaka 565, Japan
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Dr Y. Enokido, as above

Abstract

The tumour suppressor p53 gene serves as a critical regulator of the cell cycle and of apoptosis following the exposure of normal cells to DNA damage. To examine the role of p53 in postmitotic CNS neurons, we cultured cerebellar neurons from normal wild-type mice and mutant p53-null mice under various conditions inducing neuronal death. When cerebellar neurons from 15- to 16-day postnatal wild-type mice were treated with ionizing radiation or DNA-damaging agents, massive neuron death occurred after 24-72 h. In contrast, neurons from p53+ mice evidently resisted γ-irradiation and some DNA-damaging agents, such as etoposide and bleomycin. On the other hand, low-K+ medium-induced apoptosis of cerebellar neurons was not affected by p53 status. Neither cell cycle progression nor DNA synthesis occurred during cell death induced by γ-irradiation and low-K+ medium, as well as in normal cultures of p53+/+ and p53-/- neurons. These results suggest that p53 is required for the apoptotic death of postmitotic cerebellar neurons induced by DNA strand breaks.

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