Ionizing Radiation Acts on Cellular Membranes to Generate Ceramide and Initiate Apoptosis

Ionizing Radiation Acts on Cellular Membranes to Generate Ceramide and Initiate Apoptosis

August 1994 | Adriana Haimovitz-Friedman, Chu-Cheng Kan, Desiree Ehleiter, Roger S. Persaud, Maureen McLoughlin, Zvi Fuks, and Richard N. Kolesnick
The study investigates the role of ionizing radiation in generating ceramide and initiating apoptosis in bovine aortic endothelial cells (BAECs). Ionizing radiation, like tumor necrosis factor α (TNF-α), rapidly hydrolyzes sphingomyelin to ceramide, which activates a ceramide-activated serine/threonine protein kinase. The elevation of ceramide levels with exogenous ceramide analogues is sufficient to induce apoptosis. Protein kinase C (PKC) activation blocks both radiation-induced sphingomyelin hydrolysis and apoptosis, and exogenous ceramide analogues restore apoptosis. Ionizing radiation directly stimulates sphingomyelin hydrolysis in membrane preparations devoid of nuclei, suggesting that the process is independent of direct DNA damage. These findings provide conclusive evidence that apoptotic signaling can be generated by interaction of ionizing radiation with cellular membranes, challenging the hypothesis that direct DNA damage mediates radiation-induced cell kill. The study suggests that primary membrane signals, in addition to nuclear signals, must be considered in evaluating the lethal effects of ionizing irradiation.The study investigates the role of ionizing radiation in generating ceramide and initiating apoptosis in bovine aortic endothelial cells (BAECs). Ionizing radiation, like tumor necrosis factor α (TNF-α), rapidly hydrolyzes sphingomyelin to ceramide, which activates a ceramide-activated serine/threonine protein kinase. The elevation of ceramide levels with exogenous ceramide analogues is sufficient to induce apoptosis. Protein kinase C (PKC) activation blocks both radiation-induced sphingomyelin hydrolysis and apoptosis, and exogenous ceramide analogues restore apoptosis. Ionizing radiation directly stimulates sphingomyelin hydrolysis in membrane preparations devoid of nuclei, suggesting that the process is independent of direct DNA damage. These findings provide conclusive evidence that apoptotic signaling can be generated by interaction of ionizing radiation with cellular membranes, challenging the hypothesis that direct DNA damage mediates radiation-induced cell kill. The study suggests that primary membrane signals, in addition to nuclear signals, must be considered in evaluating the lethal effects of ionizing irradiation.
Reach us at info@study.space
[slides and audio] Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis