| Project/Area Number |
15510187
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Microbial Chemistry Research Foundation |
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Principal Investigator |
IKEDA Yoko Microbial Chemistry Research Foundation, Microbial Chemistry Research Center, Bioactive Molecules Research Group, a research chemist, 微生物化学研究センター・生物活性推進G, 研究員 (60159639)
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| Co-Investigator(Kenkyū-buntansha) |
SAWA Ryuichi Microbial Chemistry Research Foundation, Microbial Chemistry Research Center, Molecular Structure Research Group, a chief of unit, 微生物化学研究センター・構造検討G, ユニット長 (50235454)
UMEZAWA Kazuo Keio University, Department of Applied Chemistry, Professor, 理工学部, 教授 (70114402)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | microbial product / acidic sphyngomyelinase / inhibitor / 酸性スフィンゴミエリナーゼ |
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| Research Abstract |
In the course of our screening for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, α-mangostin, cowanine and cowanol from the bark of Garcina speciosa. Among them α-mangostin inhibited the acidic sphyngomyelinase in the most selective manner. Until now α-mangostin is the only specific inhibitor against acidic sphygomyelinase. And we also found another inhibitory activity in the culture of Streptomyces sp.ML222-mF13. The organism isolated from a soil sample collected at Yokohama City. The cultured broth was centrifuged at 5,000 rpm. The supernatant was adsorbed on a HP-20 column and eluted with methanol. The obtained powder inhibited acidic SMase with IC_<50> 10-30 μg/ml but neutral SMase with IC_<50> >1,000 μg/ml. The further purification was done using silica gel column chromatography, CPC (Coil Planet Centrifuge), HPLC (reversed phase liquid chromatography, ordinary phase partition chromatography, gel permeation chromatography) and etc. But we could not obtai
… More
n the pure active principle. There are some questions about the active principle that activities are decentralized and lost even though its good stability. The most problem is very low productivity of that strain. To get up-productivity the strain was treated by a simple mono spore selection twice, but no good result was obtained. On the other hand derivatives of α-mangostin were synthesized to reduce its toxicity at Keio University. In those derivatives, benzophenone derivative and para-methoxy benzyl derivative have selective inhibitory activity on aSMase and week cell toxicity in J774.1 cells. These derivatives reduced lipid droplets (stained by Oil Red O) induced by addition of acetyl-LDL.These derivatives also have an inhibitory activity on Zn-dependent secretary sphyngomyelinase, which enhances the uptake of acetyl-LDL to macrophages. And they did not inhibit ACAT activity in vitro. The detail mechanism that two derivative of α-mangostin decrease the cellular CE level and the amounts of the droplets is not clear yet. Less
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