1996 Fiscal Year Final Research Report Summary
Study for the signal transduction of cell growth using a new immunosuppressant ISP-1
| Project/Area Number |
07457537
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KAWASAKI Toshisuke Kyoto University, Pharmaceutical Sciences, Proffessor, 薬学部, 教授 (50025706)
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| Co-Investigator(Kenkyū-buntansha) |
KOZUTSUMI Yasunori Kyoto University, Pharmaceutical Sciences, Associate Proffessor, 薬学部, 助教授 (70205425)
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| Project Period (FY) |
1995 – 1996
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| Keywords | apoptosis / immunosuppresion / sphingosine / IL-2 / cyclosporin A / serinepalmitoiltransferase / CTLL-2 / sphingolipids |
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| Research Abstract |
ISP-1 is a new type of potent immunosuppessant, the structure of which is homologous to sphingosine. ISP-1 was found to suppress the proliferation of an IL-2-dependent cytotoxic T cell line, CTLL-2, through the inhibition of serine palmitoyltransferase, which catalyzes the first step of sphingolipid biosynthesis. Flow cytometric analysis of the effect of ISP-1 revealed that the decrease in cell number induced by ISP-1 was not due to inhibition of the cell cycle progression of CTLL-2 cells but to the induction of apoptosis of the cells. The apoptosis induced by ISP-1 was inhibited by the addition of sphingosine, suggesting that this apoptosis is triggered by the decrease in the intracellular levels of sphingolipids caused by the inhibition of serine palmitoyltransferase. Another IL-2-dependent cell line, F7, which was derived from a mouse pro-B cell line, did not show ISP-1 dependent apoptosis, suggesting that the effect of ISP-1 may be specific for a certain type of T cell lineage such as CTLL-2. On the oter hand, a high dose of sphingosine by itself induced the apoptosis of CTLL-2 cells. This sphingosine-dependent apoptosis was also observed with F7 cells. Taken together, the maintenance of intracellular concentration of sphingosine and/or its biosynthetic derivative (s) is very important to prevent from apoptosis, and both the hypo-and hyper-intracellular levels induced apoptosis in CTLL-2 cells.
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