| Project/Area Number |
06557125
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Biological pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NAGASAWA Shegeharu Hokkaido Univ., Fac.Pharm.Sci., Pro., 薬学部, 教授 (70029958)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAGAWA Shuji Osaka Univ.Dept.Med.Assist., 医学部, 助手 (90273648)
SEYA Tsukasa Osaka Med.Ctr.Adult Dis.Chiet.Inv., 研究所, 主幹
NISHIMURA Hitoshi Hokkaido Univ., Fac.Pharm.Sci.Assist., 薬学部, 助手 (80241347)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Complement / Regulatory factor / Zeno-transplantation / Measles virus / Active site / Gene technology / 臓器移植 / 補体制御因子 |
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| Research Abstract |
Membrane cofactor protein, MCP,is a complement inhibitor, which prevents autologous complement attack to host cells. In addition, MCP is a receptor of measles virus. Low molecular active fragments of MCP seemed to be useful to prevent the hyper acute ejection of zeno-transplanted organs and measles virus infection. We have investigated the functional domains of MCP essential for the complement regulation and measles virus binding.
i : Functional sites of SCR of MCP
The extra cellular portion of MCP consisted of four tandem repeats of a domain nemed short consensus repeat (SCR). Experiments using biotechnological methods revealed that i ; SCR1 and 2 are essential for measles virus infection, ii ; SCR2 and 3 are essential for the ergulation of the complement activation through the classical pathway, iii ; SCR2,3, and 4 are essential for the regulation of the complement activation through the alternative pathway.
ii : Modulation of MCP functions by serine-threonine rich (ST) regions
The SCR region of MCP was followed by a short sequence rich in Ser/Thr. There are three isoforms of ST region, ST^<ABC>, ST^<BC>, and ST^C are expressed tissue-specifically. The sequence of measles virus infection and the regulatory function to the classical pathway of three ST-isoforms was ST^C>ST^<BC>>ST^<ABC>. On the other hand, the regulatory activity to the alternative pathway was ST^<ABC>>ST^<BC>>ST^C.
iii : Importance of the membrane fraction of MCP for measles virus infection
We designed a GPl-anchored form of MCP,which is devoid of membrane fraction and intracellular domain and binding to cell surface via glycosylated inositol. The GPl-anchored MCP did not mediate measles virus infection, indicating the importance of the membrane fraction of MCP for the internalization of measles virus.
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