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

FTY720, a novel immunosuppressive drug originally derived from a metabolite from Isaria sinclairii, is known to induce apoptosis in lymphocytes. In th is study, we investigated the involvement of caspases and mitochondria in F TY720-mediated apoptosis using Jurkat cells, a human T cell line. Our resul ts indicated that FTY720-induced activation of caspases 2, 3, 6, 8, 9 and 1 0, whereas caspases 1 and 5 were not activated. We also observed in the FTY 720-treated cells a loss of mitochondrial membrane potential, a release of cytochrome c into cytosol and an exposed phosphatidylserine (PS) at the out er surface of the cell membrane. Pretreatment with a peptide inhibitor, ben zyloxycarbonyl-Asp-CH2COC-2, 6-dichlorobenzene (Z-Asp-CH2-DCB), prevented a poptosis and externalization of phosphatidylserine, whereas the inhibitor d id not prevent the mitochondrial events. This suggests that caspases may pl ay a role downstream of the mitochondrial pathway. Therefore, caspase casca de in FTY720-treated cells may be initiated by activation of mitochondria. (C) 2001 Elsevier Science B.V. All rights reserved.