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Glyco-Signals in Regulatory Mechanisms For Proliferation, Differentiation, Senescence And Apoptosis of Hematopoietic Cells.

Research Project

Project/Area Number 08457270
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionHokkaido University

Principal Investigator

SAITO Masaki  Hokkaido University, School of Medicine, Professor, 医学部, 教授 (60012762)

Co-Investigator(Kenkyū-buntansha) YABUNAKA Noriyuki  Hokkaido University, School of Medicine, Associate, 医学部, 助手 (70240637)
ISHII Atsushi  Hokkaido University, School of Medicine, Associate, 医学部, 助手 (20232225)
OHTA Masatsugu  Hokkaido University, School of Medicine, Associate Professor, 医学部, 助教授 (90160514)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥6,400,000 (Direct Cost: ¥6,400,000)
KeywordsExtracellular Matrix (ECM) glycoproteins / Fibronectin / Tenascin C / Monocytic differentiation / Granulocytic differentiation / Integrin VLA-5 / Programd cell death (Apoptosis) / Stromal-epithelial interactions / シアル酸転移酵素-I / II型膜蛋白質 / 細胞周期 / 細胞外マトリックス糖蛋白 / インテグリンVLA-5 / 単球系分化 / 顆粒球系分化 / 細胞死アポトーシス / 間質・上皮間相互作用
Research Abstract

During the period from 1996 to 1997, the following new findings were obtained, and most of them were presented in some of the international conferences, and published in the specialized journals : (1) The interaction of the extracellular matrix glycoprotein, fibronectin, with the integrin VLA-5 was shown to be intimately related with the apoptotic phenomena of hematopoietic cells. (2) A significant enhancement of the expression of VLA-5 mRNA was observed only in the monocytic, but not granulocytic, differentiation of human myelogenous leukemia HL-60 cells. (3) The expression of integrin VLA-5 on the cell surface was enhanced exclusively in the process of monocytic differentiation, and the most prominent expression was observed on the surface of peripheral mature monocytes. (4) The sensitivity of fibronectin-induced apoptosis was remarkably increased during monocytic differentiation, and the anti-VLA-5 monoclonal antibody or the RGD peptide completely abolished it. (5) Apoptosis of the … More normal monocytes, but not granulocytes, from peripheral blood was significantly increased by the extracellular matrix fibronectin, and the anti-fibronectin monoclonal antibody suppressed the apoptosis and increased the survival time of normal monocytes. (6) Expression of the extracellular matrix glycoprotein, tenascin, was restricted spatially and temporally during the formation of tumor tissues, depending upon the stromal-epithelial interactions, and the de novo synthesis of tenascins was induced by the soluble growth factor EGF,being also dependent on the stromal-epithelial interactions. Human tenascin C is shown to have the EGF-like domain, but this domain and its derivative peptide could not induce the expression of tenascin. (7) With all the current data taken together, it is concluded that the ECM glycoprotein fibronectin might play an important role as the negative regulator for the survival of monocytes in collaboration with the integrin VLA-5, which characteristically increases during the process of monocytic differentiation.
In the latter part of the present research projects, the following novel findings were demonstrated : (8) Using the elaborately-devised expression cloning method, we have succeeded for the first time in isolating and molecularly characterizing a new and relevant gene (cDNA and its genome) which encodes a key glycosyltransferase, ganglioside GM3 synthase (sialyltransferase-1) , responsible for the biosynthesis of a ubiquitous but intriguing membraneous molecule of the simplest structure, ganglioside GM3. GM3 was previously demonstrated to exhibit a variety of biological functions intimately related to the cell growth control, malignant transformations, the cell-to-cell recognitions, and the differentiation-induction of human myelogenousleukemia cells. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Nakamura, M., Saito, M., et al.: "Rapid Internalization of Exogenous Ganglioside GM3 and Its Metabolism to Ceramide in Human Myelogenous Leukemis HL-60 Cells----" FEBS Lett.400. 350-354 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakamura, M., Saito, M., et al.: "CMP-NeuAc:Galβ1→4GlcNAcα2→6Sialyl transferase Catalyzes NeuAc Transfer to Glycolipids." J.Lipid Red.38. 1795-1806 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohta, M., Saito, M., et al.: "Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice." Blood.(in press)(June 1). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ishii, A., Saito, M., et al.: "Expression Cloning and Molecular Characterization of Human Ganglioside GM3 Synthase (Sialyltransferase-1,CMP-N-acethylneuraminic---" Nature. (in revision). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mei Xu, Saito, M., et al.: "A Severe Clinical Phenotype of Maroteaux-Lamy Syndrome Caused by A Nonsense Point Mutation in Arylsulfatase B Gene." Human Genet.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 斎藤 政樹: "糖鎖生物学(蛋白質核酸酵素増刊号)" 共立出版株式会社(印刷中), 250 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 斎藤 政樹: "医科分子生物学改訂第3版(村松正美、谷口維紹編)" 南江堂, 501 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakamura, M., Saito, M., et al.: "Rapid Internalization of Exogenous Ganglioside GM3 and Its Metabolism to Ceramide in Human Myelogenous Leukemia HL-60 Cells Comparing with Control Gangliside GMl." FEBS Lett.400. 350-354 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakamura, M., Saito, M., et al.: "CMP-NeuAc : Galbeta1*4GlcNAcalpha2*6Sialyltransferase Catalyzes NeuAc Transfer to Glycolipids." J.Lipid Res.38. 1795-1806 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohta.M., Saito.M., et al.: "Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice." Blood. (in press.) (June l). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ishii, A., Saito, M., et al.: "Expression Cloning and Molecular Characterization of Human Ganglioside GM3 Synthase (Sialyltransferase-1, CMP-N-acethylneuraminic acid : lactosylceramide alpha2*3sialyltransferase, EC 2.4.99.9) that Catalyzes the First Sialylation Step of Ganglio-series Ganglioside Synthesis." Nature. (in revision). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mei Xu, Saito, M., et al.: "A Severe Clinical Phenotype of Maroteaux-Lamy Syndrome Caused by A Nonsense Point Mutation in Arylsulfatase B Gene." Human Genet.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Saito, M.: Glycobiology, In. "Protein, Nucleic Acid and Enzyme" , Special Edition (Ed by Saito, M.). Kyoritsu syuppan, Tokyo, (in press), (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Saito, M.: Structure and Function of the Cells.In "Molecular Biology in Medicine, 3rd Ed. (Eds by Muramatsu, M.and Taniguchi, T.). Nankodo, Tokyo, 250 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakamura,M., Saito,M., et al.: "Rapid Internalization of Exogenous Ganglioside GM3 and its Metabolism to Ceramide in Human Myelogenous Leukemia HL-60 Cells---" FEBS Lett.400. 350-354 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura,M., Saito,M., et al.: "CMP-NeuAc:Galβ1→4GlcNacα2→6Sialylransferase Catalyzes NeuAc Transfer to Glycolipids." J.Lipid Res.38. 1795-1806 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohta,M., Saito,M,. et al.: "Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice." Blood,. (in press). (June 1) (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishii,A., Saito,M., et al.: "Expression Cloning and Molecular Characterization of Human Ganglioside GM3 Synthase(Sialyltransferase-1,CMP-N-acethylneuraminic---" Nature. (in revision). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mei Xu, Saito,M,. et al.: "A Severe Clinical Phenotype of Maroteaux-Lamy Syndrome Caused by A Nonsense Point Mutation in Arylsulfatase B Gene." Human Genet.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 斎藤政樹: "糖鎖生物学(蛋白質核酸酵素増刊号)" 共立出版株式会社(印刷中), 250 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 斎藤政樹: "医科分子生物学 改定第3版(村松正美、谷口維紹編)" 南江堂, 501 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Saito, M.: "Purification and Characterization of Heparan Sulfate 2-Sulfotransferase from Cultured Chinese Hamster Ovary Cells" J. Biol. Chem.271. 7645-7653 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Saito, M.: "Interleukin-3-associated ganglioside GD1a is induced independently of normal interleukin-3 receptor in murine myelogenous leukaemia NFS60 cells transfected with the interleukin-3 gene" Glycoconjugate J.13. 255-261 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Saito, M.: "Therapy-Related Chronic Myelomonocytic Leukaemia with Bone Marrow Eosinophilia Associated with der (11) t (1 ; 11) (q21 ; q14)." Acta Haematol.96. 251-254 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Saito, M.: "Rapid Internalization of Exogenous Ganglioside GM3 and Its Metabolism to Ceramide in Human Myelogenous Leukemia HL-60 Cells Comparing with Control Gangliside GM1" FEBS Lett.400. 350-354 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohta M,: "Suppression of hematopoietic activity in tenascin-C gene knocked-out mice" Molecular and cellular Biology. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 斎藤政樹: "医科分子生物学改訂第3版(村松正實、谷口維紹編集)" 南江堂, 501 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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