| Project/Area Number |
09460047
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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 |
応用微生物学・応用生物化学
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| Research Institution | TOKYO INSTITUTE OF TECHNOLOGY |
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Principal Investigator |
NAGAI Kazuo Tokyo Inst.Technol., Dept.Bioengineering, Professor, 生命理工学部, 教授 (00011974)
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| Co-Investigator(Kenkyū-buntansha) |
WOO Je-Tae Tokyo Inst.Technol., Dept.Bioengineering, Assistant Professor, 生命理工学部, 助手 (20272693)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | Biologically active compound / Immunomodulator / Bone metabolism / Osteoclast / Cytotoxic Tcell / Vacuolar type H^+-ATPase / Bioprobe |
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| 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.
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