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
• 负责人: FURUKAWA Yuji
• 金额: $ 1.92万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09660128/
• 关键词: LCAT; oxidized LDL; oxidized sterol; anti-atherosclerolemic action; vitamin C; lipoproteins

This study was designed to clarify the effects of free radical generation on the activity of lecithin-cholesterol acylyransferase(LCAT). A free radical initiator. 2,2'-azobis -amidino propane dihydrochloride(AAPH), inhibited the activity of plasma LCAT as a function of the incubation time after its addition. When the small amount of oxidized LDL or HDL were added to plasma, LCAT activity was dose dependently inhibited. To identify the effects of HDL oxidation on LCAT activity, a purified enzyme and cofactor in a vesicle solution(an artificial substrate) were used.1) LCAT activity was inhibited by the oxidation of substrate vesicles, this inhivition being related to the degree of oxidation.2) This inhibition was observed even if apolipoprotein A-I was not oxidized.3) Oxidized phosphatidylcholine, but not oxidized cholesterol, in the vesicles affected LCAT activity.4) The addition of 0-40% of oxidized vesicles to normal substrate vesicles resulted in the activity of LCAT being inhibited in a dose-dependent manner.These result suggest that the esterification of cholesterol by LCAT may be affected by the oxidation of substrate phosphstidylcholine via free radical generation in the plasma.

本研究旨在阐明自由基的产生对卵磷脂-胆固醇酰基转移酶(LCAT)活性的影响。自由基引发剂。2，2‘-偶氮氨基丙烷二盐酸盐(AAPH)对血浆LCAT活性有抑制作用，且呈孵育时间依赖性。当血浆中加入少量氧化型低密度脂蛋白或高密度脂蛋白时，LCAT活性呈剂量依赖性抑制。为了确定高密度脂蛋白氧化对LCAT活性的影响，使用了囊泡溶液(人工底物)中的纯化酶和辅因子。1)底物小泡的氧化抑制了LCAT活性，这种抑制与氧化程度有关。2)即使载脂蛋白A-I没有被氧化，也能观察到这种抑制。3)氧化的磷脂酰胆碱，而不是氧化的胆固醇，4)在正常底物囊泡中加入0-40%的氧化小泡，LCAT活性受到抑制，且呈剂量依赖关系。这些结果表明，LCAT的胆固醇酯化反应可能是通过氧化底物磷脂酰胆碱在血浆中产生自由基来影响的。

项目成果

Y.Furukawa et al.: "Inhibitory Effects of lipid Oxidation on the Activity of plasma LCAT" Biosci.Biotechnol.Biochem.65 (5). 941-946 (1998)

Y.Furukawa 等人：“脂质氧化对血浆 LCAT 活性的抑制作用”Biosci.Biotechnol.Biochem.65 (5)。

S.kamiyama, T.Yamato and Y.Furukawa: "Inhibitory effects of lipid oxidation on the activity of plasma lecithin-cholesterol acyltransferase." Biosci.Biotech.Biochem.62 (5). 941-946 (1998)

S.kamiyama、T.Yamato 和 Y.Furukawa：“脂质氧化对血浆卵磷脂胆固醇酰基转移酶活性的抑制作用。”

Y.Furukawa et al.: "Antioxidative properties of LCAT in oxidative modifi of lipoproteins" Biosci.Biotechnol.Biochem.発表予定.

Y. Furukawa 等人：“脂蛋白氧化修饰中 LCAT 的抗氧化特性”Biosci.Biotechnol.Biochem.待提交。

Y.Furukawa et.al.: "Inhibitory effects of lipid oxidation on the activity of plasma LCAT" Biosci.Biotech.Biochem.62・5. 941-946 (1998)

Y.Furukawa等人：“脂质氧化对血浆LCAT活性的抑制作用”Biosci.Biotech.Biochem.62·5(1998)。