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

氧化的低密度脂蛋白（OXLDL）被认为是动脉粥样硬化的关键因素。在OXLDL中形成的氧化磷脂酰胆碱（OXPC）应该是动脉粥样硬化的关键化合物，因为它们参与了巨噬细胞的识别，并且能够激活内皮细胞和其他血管细胞。我们通过利用抗OXPC单克隆抗体DLH3（在各种类型的OXLDL制剂中的OXPC-APOB复合物和OXPC生成的代谢命运）进行了研究。人动脉粥样硬化病中的FOAM细胞与DLH3和Anti-apob Antbobs coimation coimations cocy cocy cocy cocy cocy cocy cocy cocy cocy cocy cocy cocompation cocompation cocompation cocompation cocy cocigation cocigation cocigation。仔细测量J774巨噬细胞中存在的OXPC-APOB COOMPLEX的量表明，在细胞中积累了巨噬细胞所吸收的一部分OXLDL。当细胞内细胞器在蔗糖上分级时，在次级溶酶体部分中回收了部分降解的OXLDL（小于100 kDa）……更多的密度梯度。 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 regulations, is reported to be a good model for physical OxLDL.We introduced a sensitivity Methos to measure free OxPCs containing aldehyde group by converting them to用1个，4-环己二酮处理后的荧光衍生物。 MM-LDL是通过在4℃处与FESO4一起孵育LDL来制备的。尽管MM-LDL的整个颗粒的修改状态似乎是非常现代的，从TBARS值和对琼脂糖凝胶的Elecromisity来判断，但MM-LDL中产生的自由和复杂形式的OXPC的数量比铜处理的OXLDL更高，而不是铜处理的OXLDL。 OXPC在OXLDL中形成，用于动脉粥样硬化。较少的