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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Role of the ceramide-signaling pathways in ionizing radiation-induced apoptosis

Jean-Philippe Vit1, Filippo Rosselli

  • 11UPR 2169 CNRS, Institut Gustave Roussy IFR 54, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.

Oncogene
|December 4, 2003
PubMed

Insights

Ionizing radiation (IR) triggers two pathways causing ceramide spikes, crucial for cell death. The late ceramide increase, dependent on DNA damage and ATM, is key to IR-induced apoptosis.

Area of Science:

  • Cellular Biology
  • Radiation Oncology
  • Biochemistry

Background:

  • Ionizing radiation (IR) causes cellular damage, but the signaling pathways determining cell fate are debated.
  • Understanding IR-induced cell death is vital for radiation therapy and diagnostics.

Purpose of the Study:

  • To elucidate the signaling pathways and molecular mechanisms underlying IR-induced cell death.
  • To investigate the role of intracellular ceramide in mediating IR's effects on cell fate.

Main Methods:

  • Investigated IR-induced cellular responses and signaling pathways.
  • Measured intracellular ceramide levels at different time points post-IR.
  • Utilized assays to assess DNA damage and enzyme activation (acid sphingomyelinase, ceramide synthase).
  • Examined the role of ATM signaling in the ceramide accumulation pathway.

Main Results:

  • IR exposure induces two independent signaling pathways leading to a biphasic increase in intracellular ceramide.
  • An early, transient ceramide increase occurs via DNA damage-independent acid sphingomyelinase activation.
  • A later, sustained ceramide accumulation depends on DNA damage-induced ceramide synthase activation, involving ATM.
  • The late ceramide accumulation is essential for and rate-limiting to IR-induced apoptosis.

Conclusions:

  • Ceramide acts as a critical mediator in the apoptotic process initiated by ionizing radiation.
  • IR-induced apoptosis involves a complex interplay of signaling pathways converging on ceramide metabolism.
  • Ceramide accumulation is a key determinant of cell fate following IR exposure.

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