| Project/Area Number |
02454507
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Tokyo University |
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Principal Investigator |
KODAMA Tatsuhiko Tokyo University 3rd. Dept Internal Medicine, 医学部(病)第三内科, 助手 (90170266)
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| Co-Investigator(Kenkyū-buntansha) |
松橋 信行 東京大学, 医学部(病)第三内科, 助手 (10221590)
NOBUYUKI Matsuhashi Tokyo University 3rd Dept Internal Medicine
油谷 浩幸 東京大学, 医学部・附属病院・第三内科, 助手 (10202657)
金森 博 国立健康栄養研究所, 臨床栄養部, 科学技術特別研究員 (60211851)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1991: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1990: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Macrophage / Scavenger Receptor / Foam Cell / Atherosclerosis / Cholesterol / Low Density Lipoproteins / スカベンジャ-受容体 / 変性LDL / コラ-ゲン |
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| Research Abstract |
In order to elucidate the mechanism of cholesterol deposition during the atherogenesis, we analyzed the structure and functions of macrophage scavenger receptors. These informations provide us a new insight into the treatment and prevention of atherosclerosis through the inhibition of LDL modofication and foam cell formation.
1. Primary structure of human, murine and rabbit macrophage scavenger receptors were determined and the common domain structure was confirmed.
2. Complementary DNA for macrophage scavenger receptors were transfected into COS cells and human erythro leukemia (HEL) cells. The ligand binding of macrophage scavenger receptors were mediated by the C-terminal region of collagen-like domain containing a cluster of positively charged amino acids. There is a possible endocytosis signal in the cytoplamic domain, and the sequence essential for recycling of the receptor localized in the alpha herical coiled coil domain.
3. The scavenger receptor gene is on the chromosome 8 and is bigger than 100 kb. It contains 11 exons, and two types of receptor mRNAs are generated from the alternative splicing of the single gene.
4. The transgenic mouse strains expressing either bovine type I receptor or type II receptor were established.
5. A screening method for the selection of effective LDL antioxidant was established. Using this method, the requirments for the drug which prevent the LDL modifications were determined.
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