Effects of ceramide inhibition on radiation-induced apoptosis in human leukemia MOLT-4 cells.
In the present study, using inhibitors of ceramide synthase (fumonisin B1), ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in X-ray-induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase (DGK) assay showed that the intracellular concentration of ceramide increased time-dependently after X irradiation of cells, and this radiation-induced accumulation of ceramide did not occur prior to the appearance of apoptotic cells. Treatment with D609 significantly inhibited radiation-induced apoptosis, but did not inhibit the increase of intracellular ceramide. Treatment with desipramine or GW4869 prevented neither radiation-induced apoptosis nor the induced increase of ceramide. On the other hand, fumonisin B1 and L-cycloserine had no effect on the radiation-induced induction of apoptosis, in spite of significant inhibition of the radiation-induced ceramide. From these results, it was suggested that the increase of the intracellular concentration of ceramide was not essential for radiation-induced apoptosis in MOLT-4 cells.
Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Eriko
E
Takahashi
Osamu
O
Inanami
Taketoshi
T
Asanuma
Mikinori
M
Kuwabara
D017209:Apoptosis / Q000528:radiation effects; D002518:Ceramides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D002518:Ceramides