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Mol. Cells 2002; 14(3): 332-338

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

Different Mechanisms for Membrane and Nuclear Damages in Apoptosis Induced by an Immunosuppressant, FTY720

Hiroo Nakajima, Yun-Sik Lee, Tetsuro Matsuda, Naruhiko Mizuta, Junji Magae

Abstract

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

Article

Research Article

Mol. Cells 2002; 14(3): 332-338

Published online December 31, 2002

Copyright © The Korean Society for Molecular and Cellular Biology.

Different Mechanisms for Membrane and Nuclear Damages in Apoptosis Induced by an Immunosuppressant, FTY720

Hiroo Nakajima, Yun-Sik Lee, Tetsuro Matsuda, Naruhiko Mizuta, Junji Magae

Abstract

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
Jun 30, 2023 Vol.46 No.6, pp. 329~398
COVER PICTURE
The cellular proteostasis network is adaptively modulated upon cellular stress, thereby protecting cells from proteostasis collapse. Heat shock induces the translocation of misfolded proteins and the chaperone protein HSP70 into nucleolus, where nuclear protein quality control primarily occurs. Nuclear RNA export factor 1 (green), nucleolar protein fibrillarin (red), and nuclei (blue) were visualized in NIH3T3 cells under basal (left) and heat shock (right) conditions (Park et al., pp. 374-386).

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