权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Generation and metabolism of oxidized phospholipids which are active components in oxidized low density lipoprotein.

氧化磷脂的生成和代谢，氧化磷脂是氧化低密度脂蛋白的活性成分。

基本信息

批准号：
11672184
负责人：
ITABE Hiroyuki
金额：
$ 2.3万
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：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672184/
关键词：
Oxidized LDL Foam cells Macrophages Monoclonal antibody Oxidized PC Atherosclerosis Lysosomes MM-LDL 微小酸化LDL 泡沫細胞リソゾーム

项目摘要

Oxidized low density lipoprotein (OxLDL) is believed to be a cruicial factor for atherogenesis. Oxidized phosphatidylcholines (OxPC) formed in OxLDL should be key compounds for atherogenesis, since they are involved in recognition by macrophages and are capable of activating endothelial cells and other vascular cells. We investigated, by utilizing an anti-OxPC monoclonal antibody, DLH3, the metabolic fate of OxPC-apoB complex in foam cells and OxPC generation in various types of OxLDL preparations.Foam cells in human atherosclerotic lesions were simultaneously stained immunohistochemically with DLH3 and anti-apoB antibody, indicating accumulation of OxPC-apoB coomplex. Careful measurement of the amounts of OxPC-apoB coomplex present in J774 macrophages revealed that a part of OxLDL taken up by macrophages were accumulated in the cells. Partially degraded OxLDL (less than 100 kDa) were recovered in secondary lysosome fractions when intracellular organelles were fractionated on a sucrose … More density gradient. These observations provide a metabolic rationale why and how OxLDL-related antigens are accumulated in foam cells in atherosclerotic lesions.Recently, minimally modified LDL (MM-LDL), which is prepared by moderate oxidation contitions, is reported to be a good model for physiological OxLDL.We introduced a sensitve methos to measure free OxPCs containing aldehyde group by converting them to fluorescent derivertives after treatment with 1, 4-cyclohexanedione. MM-LDL was prepared by incubating LDL with FeSO4 at 4℃. Although modification status of whole particles for MM-LDL seemed to be very moderate judging by TBARS values and eleclromobility on agarose gel, the amounts of free and complex forms of OxPC generated in MM-LDL were rather higher than copper-treated OxLDL.It is certainly needed to test the biological properties of the MM-LDL preparations as the next step, but this observation might be a interesting clue to elucidate the contribution of OxPC formed in OxLDL for atherogenesis. Less

氧化型低密度脂蛋白（OxLDL）被认为是动脉粥样硬化形成的关键因素。OxLDL中形成的氧化磷脂酰胆碱（OxPC）应该是动脉粥样硬化形成的关键化合物，因为它们参与巨噬细胞的识别，并能够激活内皮细胞和其他血管细胞。应用抗OxPC单克隆抗体DLH 3研究了泡沫细胞中OxPC-apoB复合物的代谢命运和不同类型OxLDL制剂中OxPC的产生，同时用DLH 3和抗apoB抗体对人动脉粥样硬化病变中的泡沫细胞进行化学染色，表明OxPC-apoB复合物的积累。仔细测量J774巨噬细胞中存在的OxPC-apoB复合物的量，发现巨噬细胞摄取的OxLDL的一部分在细胞中积累。部分降解的OxLDL（小于100 kDa）在次级溶酶体组分中回收，当细胞内细胞器在蔗糖上分级分离时， ...更多信息密度梯度近年来，通过适度氧化修饰的低密度脂蛋白（MM-LDL）被报道是一种很好的生理性OxLDL模型，我们介绍了一种灵敏的方法，通过用1，4-环己二酮。将LDL与FeSO_4在4℃孵育制备MM-LDL。虽然从TBARS值和琼脂糖凝胶上的电迁移率来看，MM-LDL的整个颗粒修饰状态似乎非常温和，但MM-LDL中产生的游离和复合形式的OxPC的量比铜处理的OxLDL高得多。但这一观察结果可能是阐明OxLDL中形成的OxPC在动脉粥样硬化形成中的作用的有趣线索。少