Mol. Cells 2002; 14(3): 332-338
Published online January 1, 1970
© The Korean Society for Molecular and Cellular Biology
A novel immunosuppressant, FTY720, that was purified from cultures of Isaria sinclairii has been shown to cause apoptosis of lymphocytes, but its biochemical and molecular mechanisms are largely unknown. In this study, we investigated the signal transduction of FTY720-induced apoptosis in comparison with the Fas-induced apoptosis. Although FTY720 induced nuclear and membrane damages in a dose-dependent manner, nuclear damage, but not membrane damage, was suppressed by the caspase-3 inhibitor, DEVD-FMK. It blocked both the nuclear and membrane damages that were induced by the anti-Fas antibody. Experiments using enucleated cytoplasts also demonstrated that membrane damage was induced by FTY720. However, the ones that were induced by the anti-Fas antibody were not blocked by DEVD-FMK. Exogenously-added sphingolipids partially suppressed the FTY720-induced membrane damage. These results suggest that FTY720 induces membrane damage through the caspase-3-independent pathway that is modulated by sphingolipids.
Keywords Sphingolipid, Apoptosis, Cytoplast, Caspase, FTY720
Mol. Cells 2002; 14(3): 332-338
Published online December 31, 2002
Copyright © The Korean Society for Molecular and Cellular Biology.
Hiroo Nakajima, Yun-Sik Lee, Tetsuro Matsuda, Naruhiko Mizuta, Junji Magae
A novel immunosuppressant, FTY720, that was purified from cultures of Isaria sinclairii has been shown to cause apoptosis of lymphocytes, but its biochemical and molecular mechanisms are largely unknown. In this study, we investigated the signal transduction of FTY720-induced apoptosis in comparison with the Fas-induced apoptosis. Although FTY720 induced nuclear and membrane damages in a dose-dependent manner, nuclear damage, but not membrane damage, was suppressed by the caspase-3 inhibitor, DEVD-FMK. It blocked both the nuclear and membrane damages that were induced by the anti-Fas antibody. Experiments using enucleated cytoplasts also demonstrated that membrane damage was induced by FTY720. However, the ones that were induced by the anti-Fas antibody were not blocked by DEVD-FMK. Exogenously-added sphingolipids partially suppressed the FTY720-induced membrane damage. These results suggest that FTY720 induces membrane damage through the caspase-3-independent pathway that is modulated by sphingolipids.
Keywords: Sphingolipid, Apoptosis, Cytoplast, Caspase, FTY720
Myoung-Sook Koo, Young-Guen Kwon, Joon-Hong Park, Won-Jin Choi, TimothyR. Billiar, Young-Myeong Kim
Mol. Cells 2002; 13(2): 194-201Youngleem Kim, Dai-Wu Seol
Mol. Cells 2003; 15(3): 283-293Md. Asaduzzaman Khan, Han-chun Chen, Xin-xing Wan, Mousumi Tania, Ai-hua Xu, Fang-zhi Chen, and Dian-zheng Zhang
Mol. Cells 2013; 35(3): 219-225 https://doi.org/10.1007/s10059-013-2259-z