Abstract
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.
References
Jan 27, 1996·Transplantation·S SuzukiK Chiba
Apr 1, 1996·The Journal of Experimental Medicine·N ZamzamiG Kroemer
Jun 14, 1996·Cell·A Fraser, G Evan
Jul 12, 1996·Cell·X LiuX Wang
Oct 1, 1996·The Journal of Experimental Medicine·S A SusinG Kroemer
Sep 1, 1996·Immunopharmacology·S EnosawaH Amemiya
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·S M SrinivasulaE S Alnemri
Dec 1, 1996·Immunology·S SuzukiT Shinomiya
Jan 1, 1997·Immunology Today·G KroemerS A Susin
Feb 21, 1997·Science·J YangX Wang
Feb 21, 1997·Science·R M KluckD D Newmeyer
Sep 1, 1996·The Journal of Experimental Medicine·P MarchettiG Kroemer
Feb 1, 1997·Transplantation Proceedings·X K LiS Suzuki
Jul 7, 1997·The Journal of Experimental Medicine·S A SusinG Kroemer
Aug 1, 1997·Immunology·T ShinomiyaS Suzuki
Dec 9, 1997·Cell·P LiX Wang
Dec 11, 1997·Cell·J C Reed
Feb 28, 1998·The EMBO Journal·E Bossy-WetzelD R Green
May 2, 1998·The EMBO Journal·C ScaffidiM E Peter
May 23, 1998·The Journal of Experimental Medicine·I MarzoG Kroemer
Jun 20, 1998·The Journal of Biological Chemistry·T KuwanaS Kornbluth
Aug 8, 1998·Cell·J J ChouG Wagner
Aug 26, 1998·Biochimica Et Biophysica Acta·S A SusinG Kroemer
Sep 2, 1998·Transplantation Proceedings·T MatsudaT Oka
Dec 5, 1998·Transplantation Proceedings·K SuzukiS Suzuki
Dec 10, 1998·Cell Death and Differentiation·J ZhuangG M Cohen
Dec 16, 1998·The Journal of Biological Chemistry·S FuldaK M Debatin
Dec 22, 1998·The Journal of Experimental Medicine·D MevorachK B Elkon
Jan 5, 1999·The Journal of Experimental Medicine·G MacDonaldA H Greenberg
Jan 29, 1999·The Journal of Cell Biology·E A SleeS J Martin
Feb 13, 1999·The Journal of Biological Chemistry·X M SunG M Cohen
Mar 20, 1999·Transplantation Proceedings·T SuzukiS Todo
May 9, 2000·The Journal of Biological Chemistry·T TatsutaJ D Mountz
Citations
May 11, 2007·Archives of Pharmacal Research·Mi Young AhnKang Sun Ryu
Mar 13, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Xiangfeng ZengYaoying Zeng
Aug 6, 2009·Cytotechnology·Puneet ChopraAbhijit Ray
May 15, 2012·Molecular Biology Reports·Jingyu JiangJianhua Zhou
Aug 28, 2003·Current Opinion in Chemical Biology·Hugh Rosen, Jiayu Liao
Nov 14, 2002·British Journal of Pharmacology·Yukitoshi NagaharaTakahisa Shinomiya
Oct 30, 2004·Journal of Toxicology and Environmental Health. Part a·Mi Young AhnByung Mu Lee
Mar 6, 2003·The Journal of Clinical Investigation·Yong-Mi KimMegan Sykes
Sep 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hugh RosenMichael G McHeyzer-Williams
Mar 6, 2010·Immunopharmacology and Immunotoxicology·Qingyuan Li, Feng Li
Jul 6, 2010·Transplant Immunology·Masafumi MatsumuraHideyasu Matsuyama
Oct 5, 2002·Clinics in Liver Disease·John M Vierling, Patricia A Flores
Aug 13, 2004·Life Sciences·Izzettin Hatip-Al-KhatibMichihiro Fujiwara
Aug 5, 2004·Inflammatory Bowel Diseases·Tsunekazu MizushimaHikaru Matsuda
Jun 1, 2009·Toxicological Research·Seung Jun Kwack, Byung Mu Lee