Metabolism of Oxidized Low Density Lipoprotein by Lecithin-Colesterol Acyltransferse

卵磷脂-胆固醇酰基转移酶对氧化低密度脂蛋白的代谢

基本信息

批准号：
10672056
负责人：
TAKANO Tatsuya
金额：
$ 1.73万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672056/
关键词：
atherosclerosis oxidized LDL lipoprotein oxidized PC monoclonal antibody foam cell LCAT 過酸化脂質マクロファージ

项目摘要

The possible involvement of lecithin-cholesterol acyltransferase (LCAT) in the metabolism of oxidized phosphatidylcholine (PC) in plasma was investigated. A variety of oxidized products are formed from PC following oxidation of low density lipoproteins (LDL). A significant increase in LDL oxidation levels in patients with familial LCAT deficiency (FLD) has been previously demonstrated by a sensitive sandwich ELISA for oxidized LDL using the monoclonal antibody DLH3 which recognizes oxidized products of PC. In the present study, we found that LCAT produces various metabolites from oxidized PC and that oxidized PC molecules in LDL particles serve as substrates. When the neutral lipid fraction was separated by TLC after the incubation of oxidized 1-palmitoyl-2-[1 ィイD114ィエD1C] linoleoyl PC with human plasma, a number of radioactive bands were formed in addition to cholesteryl ester. These products were not formed from native 1-palmitoyl-2-[1-ィイD114ィエD1C] linoleoyl PC. Plasma from FLD patie … More nts also failed to form the additional products from oxidized PC. The addition of dithio-bis(nitrobenzoate) (DTNB), an LCAT inhibitor, or the inactivation of LCAT activity by treating the plasma at 56 C for 30 min abolished the generation of these products from oxidized PC. The activity was recovered in the high density lipoprotein (HDL) fraction but not in the LDL fraction separated from normal plasma. When 1-palmitoyl-2-[1-ィイD114ィエD1C] (9-oxononanoyl) PC and 1-stearoyl-2-[1-ィイD114ィエD1C] (5-oxovaleroyl) PC, PC oxidation products that contain short chain aldehydes, were incubated with human plasma, radioactive products in the neutral lipid fraction were observed on TLC. LDL containing oxidized PC was measured by sandwich ELISA using an anti-apolipoprotein B antibody and DLH3.The reconstituted oxidized PC-LDL particles were found to have lost their ability to bind DLH3 upon incubation with HDL, while the reactivity of the reconstituted oxidized PC-LDL remained unchanged in the presence of DTNB. These results suggest that LCAT is capable of metabolizing a variety of oxidized products of PC and preventing the accumulation of oxidized PC in circulating LDL particles. Less

研究了卵磷脂 - 胆固醇酰基转移酶（LCAT）可能参与血浆中氧化磷脂酰胆碱（PC）代谢。低密度脂蛋白（LDL）氧化后，由PC形成多种氧化产物。先前，使用单克隆抗体DLH3识别PC的氧化产物，敏感的三明治ELISA对氧化LDL进行了敏感的三明治ELISA，其LDL氧化水平的显着升高已通过敏感的三明治ELISA进行了显着升高。在本研究中，我们发现LCAT从氧化的PC中产生各种代谢产物，并且LDL颗粒中的氧化PC分子用作底物。当氧化的1-甲米酰基-2- [1 d114e d1c] linoleoyl PC与人血浆中孵育后，通过TLC分离中性脂质级分，除了胆汁淤积外，还形成了许多放射性带。这些产物不是由天然1-甲米酰-2- [1-II D114 D1C] Lineoyyl PC形成的。来自FLD Patie的血浆…更多的NTS也未能从氧化PC中形成其他产品。通过在56 C下治疗血浆30分钟，添加了Dithio-bis（硝基苯甲酸酯）（DTNB）（DTNB），LCAT抑制剂或LCAT活性失活，从而消除了从氧化PC中产生的产物。在高密度脂蛋白（HDL）馏分中回收活性，但在与正常血浆分离的LDL级分中未回收。当1-甲米酰基-2- [1-II D114I D1C]（9-氧支持者）PC和1 stearoyl-2- [1-II D114I D1C]（5-Oxovaleroyl）PC氧化产物，这些PC氧化产物中包含短链醛的氧化产物，与人类质量溶液中的PC氧化产物在Hument plasma，Hotoractive On in Metractim in the Metral中孵化。通过使用抗磷脂蛋白B抗体和DLHH。通过夹心ELISA测量含有氧化PC的LDL。发现重构氧化的PC-LDL颗粒在与HDL孵育后孵育后失去了与DLH3结合的能力，而重新氧化的PC-LLDL的反应性则在dtn中存在氧化和氧化和氧化和氧化氢的反应。这些结果表明，LCAT能够代谢PC的多种氧化产物，并防止氧化PC在循环的LDL颗粒中的积累。较少的