| Project/Area Number |
12670666
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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 |
Circulatory organs internal medicine
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| Research Institution | Osaka University Graduate School of medicine |
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Principal Investigator |
SAKAI Naohiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80294073)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Kenichi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30332737)
YAMASHITA Shizuya Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (60243242)
西田 誠 大阪大学, 医学部・附属病院, 医員
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Atherosclerosis / reverse cholesterol transport / HDL receptor / macrophage / GPI-anchored protein / cholesterol efflux / high density lipoprotein / moesin |
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| Research Abstract |
We identified GPI-anchored type HDL- and apo A-I- binding protein with molecular weight of 80 KDa from human monocyte-derived macrophages by ligand blotting analysis.
Phospholipase C (PI-PLC) treatment of the cells decreased both the binding of HDL to and subsequent cholesterol efflux from the cells. From the cultured human macrophages, the 80 KDa HDL/apo A-I binding protein was purified with HDL-affmity column. The protein was digested with endopeptidase and the resultant fragments were sequenced for the determination of internal amino acid sequences. Two parts of 1 1 amino acid sequences completely matched those of moesin. Treatment of macrophages with anti-human moesin antibody blocked the binding of HDL and apo A-I as well as HDL- and apo A-I-mediated cholesterol efflux from human macrophages. Flowcytometric, immunohistochemical and two-dimensional immunoblotting analyzes using anti-moesin antibodies revealed that the moesin-like, GPI-anchored type HDL-binding protein is expressed on the cell surface and exclusively on monocyte-derived macrophages. Thus, we demonstrate that a moesin-like protein expressed on cell surface plays a crucial role in cholesterol efflux from macrophages as one of the specific HDL/apo A-I binding proteins.
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