Elimination of cell-cycle regulators during caspase-3-dependent apoptosis caused by an immunosuppressant, FTY720.

Abstract

The immunosuppressant, FTY720 causes apoptosis of lymphocytes, reduces numbers of lymphocytes in peripheral blood, and prevents infiltration of lymphocytes into allografts, which may be one of the mechanisms involved in its effects. Here we compared caspase activation and expression of cell-cycle regulators during apoptosis caused by FTY720, and Fas-stimulation in a mouse lymphoma transfected with human Fas antigen. FTY720 activated caspases-3, -8, and -9 as rapidly as did Fas-mediated apoptosis. The activation was blocked by a peptide inhibitor for caspase-3, DEVD-CHO. Fas-induced activation of caspases-8 and -9 was unaffected by the inhibitor. FTY720 eliminated proliferating cell nuclear antigen, retinoblastoma family members, differentiation regulated transcription factor polypetide-1, and cyclin H. These cell-cycle regulators were not eliminated when the peptide inhibitor was used. Dysfunction of cell-cycle regulators may play a critical role in the signal transduction pathway for activation of FTY720-mediated apoptosis.

• Authors: Yun-Sik Lee, Hiroo Nakajima, Mie Tsuruga, Junji Magae
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 67 Issue 3 Pg. 467-74 (Mar 2003) ISSN: 0916-8451 [Print] England
• PMID: 12723592 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Caspase Inhibitors
• Cell Cycle Proteins
• Immunosuppressive Agents
• Isoenzymes
• Oligopeptides
• Proliferating Cell Nuclear Antigen
• Propylene Glycols
• Retinoblastoma Protein
• Transcription Factors
• aspartyl-glutamyl-valyl-aspartal
• fas Receptor
• CASP3 protein, human
• Casp3 protein, mouse
• Caspase 3
• Caspases
• Fingolimod Hydrochloride
• Sphingosine

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 3
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Cycle (drug effects, physiology)
• Cell Cycle Proteins (antagonists & inhibitors, metabolism)
• Cell Differentiation (drug effects)
• Cell Line
• Enzyme Activation (drug effects)
• Fingolimod Hydrochloride
• Humans
• Immunosuppressive Agents (pharmacology)
• Isoenzymes (antagonists & inhibitors, metabolism)
• Lymphoma (genetics, metabolism)
• Mice
• Oligopeptides (pharmacology)
• Proliferating Cell Nuclear Antigen (metabolism)
• Propylene Glycols (pharmacology)
• Retinoblastoma Protein (antagonists & inhibitors, metabolism)
• Sphingosine (analogs & derivatives)
• T-Lymphocytes (metabolism)
• Transcription Factors (antagonists & inhibitors, metabolism)
• Transfection
• fas Receptor (metabolism)