Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis.

DOI PDF 被引用文献24件
  • A Haimovitz-Friedman
    Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021.
  • C C Kan
    Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021.
  • D Ehleiter
    Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021.
  • R S Persaud
    Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021.
  • M McLoughlin
    Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021.
  • Z Fuks
    Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021.
  • R N Kolesnick
    Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021.

抄録

<jats:p>Recent investigations provided evidence that the sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor alpha (TNF-alpha) in several hematopoietic and nonhematopoietic cells. In this pathway, TNF-receptor interaction initiates sphingomyelin hydrolysis to ceramide by a sphingomyelinase. Ceramide acts as a second messenger stimulating a ceramide-activated serine/threonine protein kinase. The present studies show that ionizing radiation, like TNF, induces rapid sphingomyelin hydrolysis to ceramide and apoptosis in bovine aortic endothelial cells. Elevation of ceramide with exogenous ceramide analogues was sufficient for induction of apoptosis. Protein kinase C activation blocked both radiation-induced sphingomyelin hydrolysis and apoptosis, and apoptosis was restored by ceramide analogues added exogenously. Ionizing radiation acted directly on membrane preparations devoid of nuclei, stimulating sphingomyelin hydrolysis enzymatically through a neutral sphingomyelinase. These studies provide the first conclusive evidence that apoptotic signaling can be generated by interaction of ionizing radiation with cellular membranes and suggest an alternative to the hypothesis that direct DNA damage mediates radiation-induced cell kill.</jats:p>

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