Activation of caspases and mitochondria in FTY720-mediated apoptosis in human T cell line Jurkat

M Fujino, XK Li, L Guo, T Amano, S Suzuki - International …, 2001 - Elsevier
M Fujino, XK Li, L Guo, T Amano, S Suzuki
International immunopharmacology, 2001Elsevier
FTY720, a novel immunosuppressive drug originally derived from a metabolite from Isaria
sinclairii, is known to induce apoptosis in lymphocytes. In this study, we investigated the
involvement of caspases and mitochondria in FTY720-mediated apoptosis using Jurkat
cells, a human T cell line. Our results indicated that FTY720-induced activation of caspases
2, 3, 6, 8, 9 and 10, whereas caspases 1 and 5 were not activated. We also observed in the
FTY720-treated cells a loss of mitochondrial membrane potential, a release of cytochrome c …
FTY720, a novel immunosuppressive drug originally derived from a metabolite from Isaria sinclairii, is known to induce apoptosis in lymphocytes. In this study, we investigated the involvement of caspases and mitochondria in FTY720-mediated apoptosis using Jurkat cells, a human T cell line. Our results indicated that FTY720-induced activation of caspases 2, 3, 6, 8, 9 and 10, whereas caspases 1 and 5 were not activated. We also observed in the FTY720-treated cells a loss of mitochondrial membrane potential, a release of cytochrome c into cytosol and an exposed phosphatidylserine (PS) at the outer surface of the cell membrane. Pretreatment with a peptide inhibitor, benzyloxycarbonyl-Asp-CH2COC-2, 6-dichlorobenzene (Z-Asp-CH2-DCB), prevented apoptosis and externalization of phosphatidylserine, whereas the inhibitor did not prevent the mitochondrial events. This suggests that caspases may play a role downstream of the mitochondrial pathway. Therefore, caspase cascade in FTY720-treated cells may be initiated by activation of mitochondria.
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