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Radiation-induced apoptosis in developing mouse retina exhibits dose-dependent requirement for ATM phosphorylation of

H L Borges1, C Chao, Y Xu

  • 1Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.

Cell Death and Differentiation
|January 31, 2004
PubMed

Insights

Ionizing radiation (IR) triggers DNA damage, activating ATM kinase and p53. This study shows ATM-p53 signaling in neonatal mouse retinal apoptosis is dose-dependent, with Ser18 phosphorylation crucial only at lower IR doses.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Radiation Biology

Background:

  • Ionizing radiation (IR) induces DNA damage, activating critical cellular responses.
  • ATM kinase is a master regulator of cellular responses to IR, phosphorylating downstream targets like p53.
  • p53 phosphorylation, particularly at Ser15/Ser18, is a key event in DNA damage response.

Purpose of the Study:

  • To investigate the role of ATM and p53 Ser18 phosphorylation in IR-induced retinal apoptosis in neonatal mice.
  • To determine if p53 Ser18 phosphorylation is essential for IR-induced retinal apoptosis across different radiation doses.

Main Methods:

  • Whole-body irradiation of neonatal mice with 2 Gy or 14 Gy IR.
  • Analysis of retinal apoptosis in wild-type, p53-haploinsufficient, and p53S18A mutant mice.
  • Assessment of ATM and p53 activation and downstream effects.

Main Results:

  • 2 Gy IR induced retinal apoptosis requiring ATM and p53, with p53 Ser18 phosphorylation playing a role.
  • Retinal apoptosis at 14 Gy IR still required ATM and p53 but was independent of p53 Ser18 phosphorylation.
  • p53-haploinsufficiency impaired the apoptotic response to 2 Gy IR.

Conclusions:

  • ATM activates p53-mediated retinal apoptosis in vivo in a dose-dependent manner.
  • Alternative ATM-p53 signaling pathways are utilized for apoptosis induction at higher IR doses.
  • p53 Ser18 phosphorylation is not universally required for IR-induced retinal apoptosis.

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