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Related Experiment Videos

Radiation and ceramide-induced apoptosis.

Richard Kolesnick1, Zvi Fuks

  • 1Laboratory of Signal Transduction, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.

Oncogene
|August 30, 2003
PubMed
Summary

Radiation exposure activates ceramide production, a signaling molecule that triggers cell death (apoptosis) through mitochondrial pathways. Understanding this ceramide signaling offers potential for modulating radiation therapy in cancer treatment.

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Anti-ceramide Single-Chain Variable Fragment Mitigates Gastrointestinal-Acute Radiation Syndrome and Improves Marrow Reconstitution, Rendering Near-Normal 90-Day Autopsies.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Radiation Biology

Background:

  • Ceramide functions as a crucial second messenger in cellular signaling pathways.
  • Emerging evidence indicates radiation directly impacts cell membranes, activating acid sphingomyelinase.
  • This activation generates ceramide via sphingomyelin hydrolysis, initiating apoptosis.

Purpose of the Study:

  • To elucidate the role of ceramide signaling in radiation-induced cellular responses.
  • To investigate the mechanisms of ceramide generation and its downstream effects.
  • To explore the potential of targeting ceramide metabolism for cancer therapy.

Main Methods:

  • In vivo genetic and pharmacologic studies.
  • Analysis of acid sphingomyelinase activation and ceramide generation.

Related Experiment Videos

  • Investigation of BAX activation and cytochrome c release.
  • Assessment of ceramide metabolite signaling (e.g., sphingosine 1-phosphate).

    • Main Results:

    • Radiation activates acid sphingomyelinase, leading to ceramide generation and apoptosis.
    • Radiation-induced DNA damage also triggers ceramide synthesis.
    • Ceramide signaling, involving BAX, regulates apoptosis via mitochondrial pathways.
    • Radiation specifically targets the acid sphingomyelinase apoptotic system in endothelial cells and oocytes, contributing to tissue damage.

    Conclusions:

    • Ceramide acts as a key mediator of radiation-induced apoptosis.
    • The balance of ceramide metabolism, including anti-apoptotic signals like sphingosine 1-phosphate, influences radiation sensitivity or resistance.
    • Targeting ceramide signaling pathways presents novel therapeutic strategies for cancer treatment by modulating radiation effects.