Antiarteriosclerosis activity due to disposal of oxidized cholesterol by plasma lecithin ; cholesterol acyltransferase reaction.
由于血浆卵磷脂处理氧化胆固醇而具有抗动脉硬化活性;
基本信息
- 批准号:11470155
- 负责人:
- 金额:$ 0.83万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B).
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Oxidative modification of low density lipoprotein (LDL) appears to play an important role in atherogenesis. Our previous studies demonstrated that Lecithin : cholesterol acyltransferase (LCAT ; EC 2.3.1.41) an important enzyme in the reverse cholesterol transport system was inhibited by oxidized LDL (ox-LDL). However the precise mechanism of inhibition of LCAT activity by ox-LDL is not clear still. In this study, we investigated the effect of ox-LDL on LCAT molecule and it's activator lipoprotein in HDL, apolipoprotein A-I (apo A-I). Purified LCAT and d>1.063 g/ml fraction of humanplasma as source of LCAT were incubated with LDL and ox-LDL for 1h at 4℃ and 37℃. LCAT was separated by gel permeation chromatography using Superose-12 gel filtration column through FPLC system. LCAT activity was found inhibited significantly only when it was separated from ox-LDL after incubation at 37℃ (inhibition was 20% and 85% of control in purified and plasma LCAT respectively). HDL was isolated form recombined plasma (d>1.063 g/ml fraction of plasma & LDL/ox-LDL) by sequential ultrcentrifugation using NaBr to adjust density. This isolated HDL was then labeled by [^<14>C]-Cholesterol-BSA emulsion and used as substrate for LCAT.Activity was found 21.18% lower in substrate group, which was previously exposed to ox-LDL, compared to control. LCAT was more susceptible to adverse effect of ox-LDL compared to apo A-I in HDL.LCAT activity was found protected by DTNB but GSH was found not afforded any protection to LCAT activity from ox-LDL.We therefore concluded that oxidation product (s) of LDL was transferred to LCAT and apo A-I in HDL at 37℃ and tightly bound to it, which caused irreversible modification to these molecules. More than one type of oxidation product was involved in the inhibition of LCAT activity, which may be follow different mechanism.
低密度脂蛋白(LDL)的氧化修饰在动脉粥样硬化形成中起着重要作用。我们前期的研究表明,氧化型低密度脂蛋白(OX-LDL)对胆固醇逆向转运系统中的重要酶卵磷脂:胆固醇酰基转移酶(LCAT;EC 2.3.1.41)具有抑制作用。然而,氧化低密度脂蛋白抑制LCAT活性的确切机制尚不清楚。本研究探讨了氧化低密度脂蛋白对LCAT分子及其在高密度脂蛋白中的激活性脂蛋白载脂蛋白A-I(apo A-I)的影响。将纯化的LCAT和d>;1.063 g/ml人血浆作为LCAT的来源,分别与低密度脂蛋白和氧化低密度脂蛋白在4℃和37℃孵育1h。采用Superose-12凝胶过滤柱,通过FPLC系统对LCAT进行凝胶渗透色谱分离。经37℃孵育后,LCAT活性仅在从氧化低密度脂蛋白中分离出来时才被显著抑制(纯化组和血浆组的抑制率分别为对照的20%和85%)。用溴化钠调节密度的序贯超速离心法从重组血浆(d>;1.063 g/ml血浆&低密度脂蛋白/氧化低密度脂蛋白)中分离高密度脂蛋白。将分离的高密度脂蛋白用[^<;14>;C]-胆固醇-BSA乳剂标记,作为LCAT的底物,发现底物组与对照组相比活性降低21.18%。在高密度脂蛋白中,LCAT比载脂蛋白A-I更容易受到氧化低密度脂蛋白的不利影响。LCAT活性被DTNB保护,而谷胱甘肽对氧化低密度脂蛋白没有任何保护作用。因此,在37℃时,低密度脂蛋白的氧化产物(S)转移到高密度脂蛋白中的低密度脂蛋白和载脂蛋白A-I,并与之紧密结合,对这些分子造成不可逆的修饰。多种氧化产物参与了对LCAT活性的抑制,可能遵循不同的机制。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
神山 伸: "酸化リポタンパク質とレシチン・コレステロールアシルトランスフェラーゼ"脂質栄養学. 18・1. 11-24 (1999)
Shin Kamiyama:“氧化脂蛋白和卵磷脂/胆固醇酰基转移酶”脂质营养学18・1。
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FURUKAWA Yuji其他文献
FURUKAWA Yuji的其他文献
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{{ truncateString('FURUKAWA Yuji', 18)}}的其他基金
Study on Understanding of Micro Adhesion Mechanism at InterfacialAdhesion Layer Between Biological Cells and Solid Surface
生物细胞与固体表面界面粘附层微观粘附机理的研究
- 批准号:
19360061 - 财政年份:2007
- 资助金额:
$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Nuclear magnetic resonance studies of magnetic properties of antiferromagnetic triangular spin system isolated in nano-meter region
纳米区反铁磁三角自旋系统磁特性的核磁共振研究
- 批准号:
18540330 - 财政年份:2006
- 资助金额:
$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Effect of Single Crystal Nano-Structured Thin Layer on Nano-Surface Integrity
单晶纳米结构薄层对纳米表面完整性的影响
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16206015 - 财政年份:2004
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$ 0.83万 - 项目类别:
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STABILIZATION ON PROCESS OF EXIMER LASER BY IN SITU MEASUREMENT OF ENERGY
能量原位测量稳定准分子激光过程
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11555044 - 财政年份:1999
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$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
GENERATING AND OBSERBATING OF SiC SUPPER LATTICE AND EXTRA SMOOTH SURFACE
SiC超晶格和超光滑表面的生成和观测
- 批准号:
11450061 - 财政年份:1999
- 资助金额:
$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
Inhibitory action of oxidized lipoproteins on the activity of plasma lecithin-cholesterol acyltransferase and the effects of the atherosclerosis lesions.
氧化脂蛋白对血浆卵磷脂胆固醇酰基转移酶活性的抑制作用及对动脉粥样硬化病变的影响。
- 批准号:
09660128 - 财政年份:1997
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$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Study on mechanism of generating an ultra flat surface by MBE
MBE产生超平坦表面的机理研究
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09450062 - 财政年份:1997
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$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Estimation of Final Shape and Accuracy of the Electron Beam Drawing Process
电子束拉伸过程的最终形状和精度的估计
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07455067 - 财政年份:1995
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$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
On the Design of Precise Linear Motion Bearing Mechanism in Vacuum
真空精密直线运动轴承机构的设计
- 批准号:
02555029 - 财政年份:1990
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$ 0.83万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
An Analysis of Anisotropic Etching Process and Prediction of Finished Profile
各向异性蚀刻工艺分析及成品轮廓预测
- 批准号:
63460084 - 财政年份:1988
- 资助金额:
$ 0.83万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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