Immunosuppressant FTY720 induces apoptosis by direct induction of permeability transition and release of cytochrome c from mitochondria.

摘要: FTY720 has immunosuppressive activity in experimental organ transplantation and shows a prompt protracted decrease of blood T lymphocytes upon oral administration. The lymphocyte vivo was mainly result FTY720-induced apoptosis. However, this apoptotic mechanism is not well understood. We examined the apoptosis lymphoma. Western blotting fluorescent caspase-specific substrate revealed that caspase-3 involved apoptosis, whereas caspase-1 not. Apoptotic cell death inhibited by pan-caspase inhibitor, Z-VAD-FMK, suggesting caspase activation essential for reduced mitochondrial transmembrane potential released cytochrome c from mitochondria intact cells as cell-free system even presence Z-VAD-FMK. As these reactions occurred before activation, we concluded directly influences functions. inhibition permeability transition Bcl-2 overexpression or chemical inhibitors prevented all events occurring system. Moreover, using system, did affect isolated nuclei cytosol. These results indicate affects triggers to induce further events.