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1996 Fiscal Year Final Research Report Summary

Study for the signal transduction of cell growth using a new immunosuppressant ISP-1

Research Project

Project/Area Number 07457537
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KAWASAKI Toshisuke  Kyoto University, Pharmaceutical Sciences, Proffessor, 薬学部, 教授 (50025706)

Co-Investigator(Kenkyū-buntansha) KOZUTSUMI Yasunori  Kyoto University, Pharmaceutical Sciences, Associate Proffessor, 薬学部, 助教授 (70205425)
Project Period (FY) 1995 – 1996
Keywordsapoptosis / immunosuppresion / sphingosine / IL-2 / cyclosporin A / serinepalmitoiltransferase / CTLL-2 / sphingolipids
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.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] S. Nakamura: "Dual roles of sphingolipids in signaling of the escape from and onset of apoptosis in a mouse cytotoxic T-cell line, CTLL-2." J. Biol. Chem.271 (3). 1255-1257 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小堤保則: "「スフィンゴシン経路」によるアポトーシスの新しい誘導機構" 生化学. 68 (6). 444-452 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Nakamura, Y.Kozutsumi, Yidi Son, Y.Miyake, T.Fujita, and T.Kawasaki: "Dual Roles of Sphingolipids in Signaling of the Escape from and Onset of Apoptosis in a Mouse Cytotoxic T-cell Line, CTLL-2." J.Biol.Chem.271(3). 1255-1257 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kozutsumi, S.Nakamura, T.Kawasaki: ""Sphingosine pathway" : A novel apoptosis inducing pathway" Seikagaku. 68(6). 444-452 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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