Inhibitory action of oxidized lipoproteins on the activity of plasma lecithin-cholesterol acyltransferase and the effects of the atherosclerosis lesions.

点击翻译按钮获取中文摘要

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.