Role of acid sphingomyelinase-induced ceramide generation in response to radiation

Radiation-induced acid sphingomyelinase (asmase) stimulation and subsequent ceramide generation are known to be involved in endothelial cell apoptosis. The molecular mechanisms regulating the endothelial response to high doses of radiation are suggested to be initiated via translocation of endothelial asmase from the inner to the outer leaflet of the plasma membrane. Further, asmase catalyzes the hydrolysis of sphingomyelin to generate the lipid second messenger ceramide that leads to the transmembrane signaling of apoptosis [1]. Studies by Garcia-Barros et al. demonstrated that mouse MCA/129 fibrosarcoma and B16F1 melanoma upon exposure to single doses of 15-20 Gray (Gy) resulted in asmase/ceramide-induced endothelial apoptosis leading to tumour cure. Conversely, tumours xenografted in apoptosis-resistant asmase knockout mice were completely resistant to the same single-dose irradiation [2]