Document Detail


T cell selective apoptosis by a novel immunosuppressant, FTY720, is closely regulated with Bcl-2.
MedLine Citation:
PMID:  12429567     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. A novel immunosuppressant FTY720 caused a significant decrease in peripheral T lymphocytes, but not in B lymphocytes upon oral administration. This decrease was mainly a result of FTY720-induced apoptosis. In this study, we confirmed FTY720-induced T cell selective apoptosis using lymphoma cell lines in vitro. 2. Viability loss, DNA fragmentation, Annexin V binding, and caspases activation (caspase-3, -8, and -9) were observed in Jurkat cells (T lymphoma cells), but not significantly in BALL-1 cells (B lymphoma cells). These results indicated that FTY720 selectively induced apoptosis in T cell lymphoma to a greater extent than in B cell lymphoma, a finding that is similar to the result observed when FTY720 was treated with T lymphocytes and B lymphocytes in vitro. 3. FTY720 released cytochrome c from mitochondria in Jurkat intact cells as well as from isolated Jurkat mitochondria directly, but not from mitochondria in BALL-1 cells nor from isolated BALL-1 mitochondria. 4. BALL-1 cells and B cells had more abundant mitochondria-localized anti-apoptotic protein Bcl-2 than did Jurkat cells and T cells. 5. FTY720-induced apoptosis is inhibited by the overexpression of Bcl-2, suggesting that the cellular Bcl-2 level regulates the sensitivity to FTY720.
Authors:
Yukitoshi Nagahara; Masahiko Ikekita; Takahisa Shinomiya
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  137     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-13     Completed Date:  2003-05-20     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  953-62     Citation Subset:  IM    
Affiliation:
Division of Radio Isotopes and Biosafety Research, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
B-Lymphocytes / cytology,  drug effects
Cell Survival / drug effects
Cytochrome c Group / secretion
Dose-Response Relationship, Drug
Humans
Immunosuppressive Agents / pharmacology*
Jurkat Cells / drug effects
Mitochondria / drug effects,  metabolism
Propylene Glycols / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / genetics,  physiology*
Rats
Sphingosine / analogs & derivatives
T-Lymphocytes / cytology,  drug effects*
Transfection
Tumor Cells, Cultured / drug effects
Chemical
Reg. No./Substance:
0/Cytochrome c Group; 0/Immunosuppressive Agents; 0/Propylene Glycols; 0/Proto-Oncogene Proteins c-bcl-2; 123-78-4/Sphingosine; 3QN8BYN5QF/fingolimod
Comments/Corrections

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