2002 Fiscal Year Final Research Report Summary
HDL stimulates the efflux of peroxidized phospholipids from foam cells and its visualization
| Project/Area Number |
13460053
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
食品科学・栄養科学
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| Research Institution | Tohoku University |
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Principal Investigator |
MIYAZAWA Teruo Tohoku University, Graduate School of Life Science and Agriculture, Professor, 大学院・農学研究科, 教授 (20157639)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Mari Tohoku University, Graduate School of Life Science and Agriculture, Assistant Professor, 大学院・農学研究科, 助教授 (50192430)
OIKAWA Shinichi Nippon Medical School, Department of Medicine, Professor, 医学部, 教授
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| Project Period (FY) |
2001 – 2002
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| Keywords | Atherosclerosis / Hyperlipidemia / Membrane phospholipid / Lipid peroxidation / Peroxidized phospholipid / Oxidized lipoprotein / Macrophage / Oxidized LDL |
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| Research Abstract |
Atherosclerosis is the process underlying coronary artery disease and cerebrovascular disease, and is a leading cause of morbidity in industrialized countries. With the aim of atherosclerosis prevention, mechanisms of atherosclerosis development as well as its protection by dietary food components have been studied worldwide. Here, we demonstrated for the first time that in patient with hyperlipidemia as a major cause of atherosclerosis, the levels of plasma phosphatidylcholine hydroperoxide (PCOOH; that is a primary oxidation product of phosphatidylcholine which located on the surface of plasma lipoprotein particle) were significantly higher than in the healthy volunteers. This indicated that hyperlipidemic patients possess a substantial amount of minimally-oxidized lipoproteins, and implied that the peroxidation of lipoprotein phospholipids would be especially important for the atherosclerotic lesion formation. In the case for using the human monocyte cell line (THP-1), macrophage-like THP-1 cells effectively phagocytized PCOOH-riched oxidized low density lipoprotein (oxLDL), which resulted in the marked accumulation of PCOOH in the cells. By the addition of high density lipoprotein (HDL) to the oxLDL-treated THP-1 cells, cellular PCOOH efficiently attenuated. Thus, we investigated the incorporation mechanism of PCOOH from oxLDL to HDL, and confirmed the ability of HDL to reduce PCOOH by in vitro cell culture experiments and ultra-sensitive LC-MS analysis. On the other hand, fluorescence-labeled PCOOH was able to prepare experimently, and investigated visualization of such PCOOH (I.e., fluorometrically monitorization of the incorporation of oxLDL into THP-1 cells). The present study confirmed that HDL revealed antioxidative function via the reduction of PCOOH.
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[Publications] Moriya K, Nakagawa K, Santa T, Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Miyazawa T, Ishibashi K, Horie T, Imai K, Todoroki T, Kimura S, Koike K: "Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis"Cancer Research. 61(11). 4365-4370 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Masuko T, Funayama Y, Naito H, Fukushima K, Shibata C, Takahashi K, Ogawa H, Ueno T, Hashimoto A, Miyazawa T, Nakagawa K, Matsuno S, Sasaki I.: "Measurement of phosphatidylcholine hydroperoxide in mild ischemia-reperfusion injury in rat intestine"Tohoku Journal of Experimental Medicine. 198(4). 223-232 (2002)
Description
「研究成果報告書概要(欧文)」より
