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Different effects of cell-permeable ceramide analogs on platelet activation
T Hashizume1, T Kageura, T Sato
1Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Japan.
Abstract:
The effects of cell-permeable ceramide analogs on platelet responses induced by agonists were investigated. When washed rabbit platelets were pretreated with ceramide and then stimulated with thrombin or U46619, C2-ceramide (N-acetylsphingosine) dose-dependently inhibited the aggregation and arachidonic acid liberation, whereas C6-ceramide (N-hexanoylsphingosine) and C8-ceramide (N-octanoylsphingosine) enhanced these responses. Furthermore, C6-ceramide, but not C2-ceramide, enhanced the increase in and prevented the progressive decrease in cytoplasmic free Ca2+ concentration induced by U46619. On the other hand, treatment with sphingomyelinase potentiated the aggregation in response to U46619. These results indicate that the effects of cell-permeable ceramide analogs on platelet activation vary with N-acyl chain length.
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