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1998 Fiscal Year Final Research Report Summary

Studies on physiological functions of vacuolar type H^+-ATPase using low molecular weight probes

Research Project

Project/Area Number 09460047
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionTOKYO INSTITUTE OF TECHNOLOGY

Principal Investigator

NAGAI Kazuo  Tokyo Inst.Technol., Dept.Bioengineering, Professor, 生命理工学部, 教授 (00011974)

Co-Investigator(Kenkyū-buntansha) WOO Je-Tae  Tokyo Inst.Technol., Dept.Bioengineering, Assistant Professor, 生命理工学部, 助手 (20272693)
Project Period (FY) 1997 – 1998
KeywordsBiologically active compound / Immunomodulator / Bone metabolism / Osteoclast / Cytotoxic Tcell / Vacuolar type H^+-ATPase / Bioprobe
Research Abstract

Effects of concanamycin B, a specific inhibitor of vacuolar type H^+-ATPase (V-ATPase), and prodigiosin 25-C, which inhibits proton pump activity of V-ATPase without affecting its ATPase activity, on acidification of acidic intracellular granules in osteoclasts and on osteoclastic bone resorption were determined. These two inhibitors suppressed the acidification of the granules as well as bone resorption. Destruxins A, B and B, which are known to inhibit proton pump activity of V-ATPase, did not inhibit acidification of acidic intracellular granules in osteoclasts. However, they inhibited osteoclastic bone resorption by inducing morphological changes of osteoclasts that are not observed in the osteoclasts treated with concanamycin B or prodigiosin 25-C.It is clearly demonstrated that the morphological changes caused by destruxins are attributable to disruption of actin rings in osteoclasts which are essential cytoskeletal structures for bone resorption. The disruptive potency of destruxin E, which contains epoxide moiety in the molecule, was 30 times more evident than that of destruxin A and B, suggesting that the epoxide plays an important role in the expression of biological activities.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Je-Tea Woo: "Prodigiosin 25-C and metacycloprodigiosin suppress the bone resorption by osteoclasts" Biosci.Biotech.Biochem.61. 400-402 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ken-ichi Togashi: "Characterization of a series of vacuolar type H^+-ATPase inhibitors on CTL-mediated cytotoxicitty" Immunol.Let.55. 139-144 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takao Kataoka: "Characterization of perforin-based and Fas-based CTL-mediated cytotoxicity by using low molecular probes" in K.Funatsu et al. (eds.) Animal Cell Technology : Basic & Applied Aspects. 8. 547-552 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Je-Tea Woo: "Low molecular weight microbial metabolites that suppress bone resorption by inhibiting vacuolar type proton pump activity of osteoclasts" in K.Funatsu et al. (eds.) Animal Cell Technology : Basic & Applied Aspects. 8. 627-632 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin-ichi Hamada: "Immunosuppressive effects of gallic acid and chebulagic acid on CTL-mediated cytotoxicity" Biol.Pharna.Bull.20. 1017-1019 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takao Kataoka: "Inactivation and proteolytic degradation of perforin within lytic granules upon neutralization of acidic pH" Immunology. 91. 493-500 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ken-ichi Togashi: "Concanamycin A, a vacuolar type H^+-ATPase inhibitor, induces cell death in activated CD8^+-CTL" Cytotechnology. 25. 127-135 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomohiko Sato: "Ptodigiosins as anew group of H^+/Cl^- symporters that uncouple proton translocators" J.Bio.Chem.273. 21455-21462 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroki Konno: "Prodigiosins uncouple mitochondorial and bacterial F-ATPases : Evidence for their H^+/Cl^- symport activity" J.Biochem.124. 547-556 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shoji Ohkuma: "Prodigiosins uncouple lysosomal vacuolar-type ATPase through promotion of H^+/Cl^- symport" Biochem.J.334. 731-741 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Je-Tea Woo, Yasuo Ohba, Kahori Tagami, Koji Sumitani, Takao Kataoka, and Kazuo Nagai: "Prodigiosin 25-C and metacycloprodigiosin suppress the bone resorption by osteoclasts" Biosci.Biotech.Biochem.61. 400-402 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ken-ichi Togashi, Takao Kataoka, and Kazuo Nagai: "Characterization of a series of vacuolar type H^+-ATPase inhibitors on CTL-mediated cytotoxicitty" Immunol.Let.55. 139-144 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takao Kataoka, and Kazuo Nagai: "Characterization of perforin-based and Fas-based CTL-mediated cytotoxicity by using low molecular probes" K.Funatsu et al.(eds.)Animal Cell Technology : Basic & Applied Aspects. 8. 547-552 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Je-Tae Woo, Yasuo Ohba, Kahori Tagami, Koji Sumitani, Kohji Yamaguchi, Tomoko Tsuji, Takao Kataoka, and Kazuo Nagai: "Low molecular weight microbial metabolites that suppress bone resorption by inhibiting vacuolar type proton pump activity of osteoclasts" K.Funatsu et al.(eds.)Animal Cell Technology : Basic & Applied Aspects. 8. 627-632 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin-ichi Hamada, Takao Kataoka, Je-Tae Woo, Atsushi Yamada, Takashi Yoshida, Toshio Nishimura, Noboru Otake, and Kazuo Nagai: "Immunosuppressive effects of gallic acid and chebulagic acid on CTL-mediated cytotoxicity" Biol.Pharma.Bull.20. 1017-1019 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takao Kataoka, Ken-ichi Togashi, Hajime Takayama, Kazuaki Takaku, and Kazuo Nagai: "Inactivation and proteolytic degradation of perforin within lytic granules upon neutralization of acidic pH" Immunology. 91. 493-500 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ken-ichi Togashi, Takao Kataoka, and Kazuo Nagai: "Concanamycin A,a vacuolar type H^+-ATPase inhibitor, induces cell death in activated CD8^+ CTL" Cytotechnology. 25. 127-135 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomohiko Sato, Hiroshi Konno, Yasufumi Tanaka, Takao Kataoka, Kazuo Nagai, Harry H.Wasserman, and Shoji Ohkuma: "Ptodigiosins as anew group of H^+/C1^- symporters that uncouple proton translocators" J.Bio.Chem.273. 21455-21462 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroki Konno, Hidekazu Matsuya, Masayuki Okamoto, Tomohiko Sato, Yasufumi Tanaka, Ken Yokoyama, Takao Kataoka, Kazuo Nagai, Harry H.Wasserman, and Shoji Ohkuma: "Prodigiosins uncouple mitochondorial and bacterial F-ATPases : Evidence for their H^+/C1^- symport activity" J.Biochem.124. 547-556 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shoji Ohkuma, Tomohiko Sato, Masayuki Okamoto, Hidekazu Matsuya, Kunizo Arai, Takao Kataoka, Kazuo Nagai, and Harry H.Wasserman: "Prodigiosins uncouple lysosomal vacuolar-type ATPase through promotion of H^+/Cl^- symport" Biochem.J.334. 731-741 (1998)

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

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Published: 1999-12-08  

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