| Project/Area Number |
10044309
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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 | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya City University |
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Principal Investigator |
YOKOYAMA Shinji Nagoya City University Medical School professor, 医学部, 教授 (10142192)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJITA Maki Nagoya City University Medical School research associate, 医学部, 助手 (10253262)
DOHMAE Sumiko (ABE Sumiko) Nagoya City University Medical School assistant professor, 医学部, 講師 (70227700)
ITO Junichi Nagoya City University Medical School associate professor, 医学部, 助教授 (60167260)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | cholesterol / phosphlipid / lipoprotein / apolipoprotein / 細胞 / 脂質 / リポタンパク質 / アポリポタンパク質 |
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| Research Abstract |
We studied the HDL assembly system mediated by apolipoprotein-cell interaction by using three model systems.
1) Study on the apolipoprotein interaction site in mouse leukemic cell line cells RAW 264. A kinase must be activated for this cell to express the binding site with apolipoprotein and to gegerate HDL with cellular lipid. It takes several hours for the full expression which is suppressed by various metabolic inhibitors for protein synthesis. Therefore, contribution of a membrane protein(s) is suggested. Interestingly, there was no apparent difference in expression of ABC1 which has been shown as a mutation site in familial HDL deficiencies.
2) Study on intracellular cholesterol trafficking linked to the HDL assembly system in human leukemic cell line cells THP-1. While THP-1 cells gegerate HDL only with cellular phospholipid by apolipoprotein before differentiation, HDL is enriched with cholesterol after PMA induces differentiation. Both ABC1 and caveolin-1 are induced by PMA, and the antisense DNA selectively reduces cholesterol content in the HDL generated. Therefore, caveolin-1 is responsible for incorporation of cholesterol into the HDL.
3) Study on physiological relevance of the HDL assembly system in a mouse model by using an inhibitor of the apolipoprotein-cell interaction, probucol. Mouse HDL is rapidly and remarkably decreased by probucol, while no significant change is demonstrated in the massages of HDL-relating proteins including ABC1 and in the HDL clearance. The HDL assembly by apolipoprotein and the peritoneal macrophage is markedly decreased by probucol, showing that this is a major source of plasma HDL in mice.
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