| Project/Area Number |
12671101
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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 |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TSUKAMOTO Kazuhisa Faculty of Medicin, The University of Tokyo, Assistant Protessor, 医学部・附属病院, 助手 (20251233)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Yoshiaki Faculty of Medicin, The University of Tokyo, Assistant Protessor, 医学部・附属病院, 講師 (40172879)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | paraoxonase I / HDL / Apolpoprotein A-I / oxidized lipia / PAF-AH / LDL / macrophage / atherosclerosis / RAF-AH / アポAI / 酸化 / 動脈硬化症 |
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| Research Abstract |
Paraoxonase 1 (PON1) is an enzyme that is associated with HDL and removes oxidized lipids from lipoproteins. In this study, we analyzed its property not only by utilizing the serum from an apoAI deficient patient but also by overexpressing PON1 protein using adenoviral-mediated gene transfer technique in mice. PON1 protein was exclusively distributed on HDL particles in apoAI deficiency, however, its stability in both the activity and localization on HDL was reduced in apoAI deficiency. Over-expression of PON1 protein in mice results in its exclusive association on HDL particles. HDL particles containing abundant PON1 protein were resistant to oxidative stress, and possessed not only protective function against foam cells formation from macrophages by oxidized LDL, but also enhancing effect for efflux of cholesterol from lipid-laden macrophages. We also evaluated the property of PAF-AH, an another lipoproteinassociated enzyme which possesses activity in catalyzing oxidized lipids as well as PON1. When over-expressed in mice, PAF-AH distributed not only on HDL particles but also on non-HDL particles. All of the lipoprotein particles abundant in PAF-AH were resistant to oxidative stress, and the HDL particles carrying excess PAF-AH possessed the same anti-atherogenic property on macrophages as was observed in HDL abundant in PON1.
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