Recognition of solubilized apoproteins from delipidated, oxidized low density lipoprotein (LDL) by the acetyl-LDL receptor.
Recognition of solubilized apoproteins from delipidated, oxidized low density lipoprotein (LDL) by the acetyl-LDL receptor.
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DOI：
10.1073/pnas.84.2.537
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发表时间：
1987
影响因子：
11.1
通讯作者：
S. Parthasarathy;L. Fong;D. Otero;D. Steinberg
中科院分区：
文献类型：
--
作者：
S. Parthasarathy;L. Fong;D. Otero;D. Steinberg
巨噬细胞表达识别乙酰化低密度脂蛋白（LDL）和某些其他化学修饰形式的LDL但不识别天然LDL的特异性受体。通过在Ham's F-10培养基中与内皮细胞孵育或通过在不存在细胞的情况下与5 μ M铜（II）离子孵育而氧化修饰的LDL被该相同受体识别。这种氧化修饰，无论是细胞诱导的还是铜催化的，都伴随着LDL物理和化学性质的许多变化，包括密度增加、磷脂酰胆碱转化为溶血磷脂酰胆碱、脂质过氧化物的产生和载脂蛋白B-100的降解。哪些变化对于引发受体识别是必需的尚不清楚。在本文件中，它表明，从脱脂，氧化LDL降解的载脂蛋白片段几乎可以定量使用正辛基β-D-吡喃葡萄糖苷resolubilized。这些125 I标记的，溶解的载脂蛋白迅速降解的小鼠腹腔巨噬细胞，降解竞争性抑制未标记的乙酰-LDL和内皮细胞修饰的LDL，但不是由本地LDL。这些结果表明，乙酰基-LDL受体识别载脂蛋白部分上的表位，无论是新产生的或暴露的氧化修饰的结果，而不是一些氧化的脂质部分。此外，结果表明，氧化修饰的LDL的脂质不发挥强制性的作用，在确定该表位的构象。
Macrophages express a specific receptor that recognizes acetylated low density lipoprotein (LDL) and certain other chemically modified forms of LDL but not native LDL. LDL oxidatively modified either by incubation with endothelial cells in Ham's F-10 medium or by incubation with 5 microM copper(II) ion in the absence of cells is recognized by this same receptor. This oxidative modification, whether cell-induced or copper-catalyzed, is accompanied by many changes in the physical and chemical properties of LDL, including an increase in density, conversion of phosphatidylcholine to lysophosphatidylcholine, generation of lipid peroxides, and degradation of apolipoprotein B-100. Which changes are essential for eliciting the recognition by the receptor is not known. In the present paper it is shown that fragments of the degraded apolipoprotein from delipidated, oxidized LDL can be almost quantitatively resolubilized using n-octyl beta-D-glucopyranoside. These 125I-labeled, solubilized apoproteins were degraded rapidly by mouse peritoneal macrophages, and that degradation was competitively inhibited by unlabeled acetyl-LDL and endothelial cell-modified LDL but not by native LDL. These results show that the acetyl-LDL receptor recognizes an epitope on the apoprotein moiety, either newly generated or exposed as a result of oxidative modification, rather than some oxidized lipid moiety. Further, the results suggest that the lipids of oxidatively modified LDL do not play an obligatory role in determining the conformation of that epitope.