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Signal transduction for apoptosis induction using apoptosis-inducing immunosuppressant

Research Project

Project/Area Number 09680588
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KOZUTSUMI Yasunori  Kyoto University Pharmaceutical Sciences Associate Professor, 薬学研究科, 助教授 (70205425)

Co-Investigator(Kenkyū-buntansha) KAWASAKI Toshisuke  Kyoto University Pharmaceutical Sciences Professor, 薬学研究科, 教授 (50025706)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsapoptosis / immunosuppressant / glycolipid / sphingolipid / kinase / signal transduction / ISP-1 / yeast / スフィンゴシン / CPP32 / Bcl-2
Research Abstract

In our previous study, the sphingosine-like immunosuppressant, ISP-1, was found to suppress proliferation of an interleukin-2-depentent cytotoxic T cell line, CTLL-2, through the inhibition of serine palmitoyltransferase, which catalyzes the committed step of sphingolipid biosynthesis. The growth inhibition induced by ISP-1 was antagonized by the addition of sphingosine. Instead of sphingosine, phytosphingsine is synthesized in the Saccharomyces cerevisiae by the similar pathway of mammalian cells, In this study, the inhibition of proliferation by ISP-1 was observed with Saccharomyces cerevisiae, and was abolished by addition of phytosphingsine. In addition, overreplication of DNA was detected in the ISP-1 treated yeast cells by flow cytometry. And we have identified a Saccharomyces cerevisiae gene, SLI2, that resisted the growth inhibition of ISP-1. The protein kinase catalytic domain is located at the carboxy-terminal portion of Sli2p. Kinase-dead mutants of SLI2 did not give any resistance to ISP-1, leading us to predict that kinase activity of Sli2p should be essential for its function in resisting ISP-1. Sli2p overexpression had no effect on serine palmitoyltransferase activity and sphingolipids metabolism. These results indicated that Sli2p may play an important role in rescuing yeast from decrease of sphingolipids induced by ISP-1.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] H., Morio et al.: "Renal expression of serum-type mannan-binding protein in rat." Eur.J.Biochem.243(3). 770-774 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T., Yamaji et al.: "Neutral glycosphingolipids induce cell-cell aggregation of a variety ofhematopoietic cell lines." Eur.J.Biochem.247(1). 21-29 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K., Terayama et al.: "Cloning and functional expression of a novelglucuronyltransferase involved in the biosynthesis of the carbohydrate epitope, HNK-1" Proc. Natl. Acad. Sci. U.S.A.94(12). 6093-6098 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H., Sakuma et al.: "Molecular Cloning and Functional Expression of a cDNAEncoding a New member of Mixed Lineage protein Kinase from Human Brain" J.Biol.Chem.272(45). 28622-28629 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E., Schmelz et al.: "Induction of apoptosis by fumonisin B1 in HT29 cells is mediated by theaccumulation of endogenous free sphingoid bases" Toxicol. Appl. Pharmacol.148(1). 252-260 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Morio, H.Kurata, R.Katsuyama, S.Oka, Y.Kozutsumi and T.Kawasaki: "Renal expression of serum-type mannan-binding protein in rat." Eur.J.Biochem.243(3). 770-774 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Yamaji, Y.Miyake, Y.Kozutsumi and T.Kawasaki: "Neutral glycosphingolipids induce cell-cell aggregation of a variety of hematopoietic cell lines." Eur.J.Biochem.247(1). 21-29 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Terayama, S.Oka, Y.Miki, A.Nakamura, Y.Kozutsumi, K.Takio and T.Kawasaki: "Cloning and functional expression of a novel glucuronyltransferase involved in the biosynthesis of the carbohydrate epitope, HNK-1" Proc.Natl.Acad.Sci.U.S.A.94(12). 6093-6098 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Sakuma, A.Ikeda, s.Oka, Y.Kozutsumi, J-P.Zanetta, and T.Kawasaki: "Molecular Cloning and Functional Expression of a cDNA Encoding a New member of Mixed Lineage protein Kinase from Human Brain" J.Biol.Chem.272(45). 28622-28629 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E.Schmelz, M.Dombrink-Kurtzman, P.Roberts, Y.Kozutsumi, T.Kawasaki, and A.Merrill: "Induction of apoptosis by fumonisin B1 in HT29 cells is mediated by the accumulation of endogenous free sphingoid bases" Toxicol.Appl.Pharmacol.148(1). 252-260 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E.Schmelz他5名: "Induction of apoptosis by fumonisin B1 in HT29 cells is mediated by theaccumulation of endogenous free sphingoid bases" Toxicol.Appl.Pharmacol.148(1). 252-260 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Irie他5名: "The Molecular Basis for the Absence of N-Glycolylneuraminic Acid in Humans" J.Biol.Chem.273(25). 5866-15871 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 山地俊之他2名: "免疫抑制剤ISP-1の作用機構" 蛋白質核酸酵素. 43(16). 2503-2509 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Ma他5名: "Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system : Mannan-binding proteindependent cell-mediated cytotoxicity" Proc.Natl.Acad.Sci.U.S.A.96(2). 371-375 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Yamaji et al: "Neutral glycosphingolipids induce cell-cell aggregation of a variety ofhematopoietic cell lines" Eur.J.Biochem.247(1). 21-29 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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