| Project/Area Number |
10672043
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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 |
Biological pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TOKUMURA Akira The University of Tokushima, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (00035560)
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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 |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | atherosclerosis / oxidized phospholipid / plateletactivating factor / lipid peroxidation / hypercholesteromia / lysophosphatidic acid / lysophospholipase D / lysophosphatidylcholine / 酸化リポタンパク / リポキシゲナーゼ / 血漿脂質 / リゾホステァチジン酸 / リゾホステァチジルコリン |
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| Research Abstract |
We examined whether oxidized phospholipids and lysophospholipids are involved in the pathogenesis of atherosclerosis, and obtained following results.
1. We characterized platelet-activating factor (PAF)-like lipids derived from PC having a linoleoyl group on reaction with soybean lipoxygenase or rabbit reticulocyte 15-lipoxygenase, and analyzed the oxidized PC by gas chromatography-mass spectrometry. Two types of PAF-like lipids (short chain dicarboxylatesemialdehyde or monocarboxylate-containing PC) were detected ; they were suggested to be generated by oxidative fragmentation of PC hydroperoxides.
2. PC containing a dicarboxylate semialdehyde residue inhibited the production of nitric oxide induced by lipopolysaccharide and interferon-γ in vascular smooth muscle cells.
3. Metal ion-dependent lysophospholipase D hydrolyzed lysophosphatidylcholine (LPC) to bioactive lysophosphatidic acid (LPA) in rat, human and rabbit plasma or serum during incubation at 37℃.
4. Lysophospholipase D in animal plasma and serum was found to hydrolyze unsaturated LPCs over unsaturated LPCs.
5. Serum lysophospholipase D activity was increased at I week after feeding a high-holesterol diet, followed by further increase at 2-3 weeks, but after 4 weeks, the activity was declined to the level before cholesterol-loading. In addition, the levels of LPC and LPA were gradually increased with the cholesterol-loading for 12 weeks.
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