Decrease in Reactive Amino Groups during Oxidation or Endothelial Cell Modification of LDL: Correlation with Changes in Receptor‐Mediated Cataboiism
Decrease in Reactive Amino Groups during Oxidation or Endothelial Cell Modification of LDL: Correlation with Changes in Receptor‐Mediated Cataboiism
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LDL氧化或内皮细胞修饰过程中反应性氨基的减少：与受体介导的分解代谢变化的相关性
DOI：
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
D. Steinberg
中科院分区：
文献类型：
--
作者：
U. Steinbrecher;J. Witztum;S. Parthasarathy;D. Steinberg
单核细胞/巨噬细胞似乎是动脉粥样硬化病变中许多脂质细胞的前体，但这些细胞积聚胆固醇成为泡沫细胞的机制尚不清楚。我们之前报道过，培养的内皮细胞可以通过一种方式修饰低密度脂蛋白（LDL），导致巨噬细胞的乙酰LDL受体快速摄取。这种修饰涉及自由基诱导LDL的过氧化，并伴随着LDL的许多物理化学性质的变化，包括电泳迁移率增加、密度增加、酯化胆固醇含量降低、磷脂酰胆碱水解和载脂蛋白b的断裂。在高度有利于氧化的条件下，即使在没有细胞的情况下，也会发生类似的修饰。在目前的研究中，仅仅暴露在5μMCu++中，LDL的氧化导致了与内皮细胞产生的修饰难以区分的修饰。此外，研究表明，无论用哪种方法氧化LDL，都伴随着氨基反应性的显著降低，这与LDL的化学修饰导致乙酰化LDL受体识别的情况相当。蛋白水解酶抑制剂不能减少载脂蛋白B在氧化过程中的碎片化。豚鼠静脉注射氧化LDL的分解速率非常快，80%以上的降解发生在肝脏。这些研究表明，所有与内皮细胞LDL修饰相关的变化都可归因于氧化。然而，这些细胞可以在氧化过程缓慢的情况下促进氧化。内皮细胞或5 μM Cu++修饰LDL导致LDL氨基反应性显著降低，这与培养细胞和体内通过乙酰型LDL受体加速LDL清除和降低经典LDL受体清除相关。
The monocyte/macrophage appears to be the precursor of many of the lipid-laden cells in atherosclerotic lesions, but the mechanism by which these cells accumulate cholesterol to become foam cells remains unclear. We have previously reported that cultured endothelial cells can modify low density lipoprotein (LDL) in a manner that leads to rapid uptake by the acetyl LDL receptor of macrophages. This modification involves free radical-induced peroxidation of LDL and is accompanied by many changes in the physicochemical properties of LDL including increased electrophoretic mobility, increased density, decreased content of esterified cholesterol, hydrolysis of phosphatidylcholine, and fragmentation of apolipoprotein B. Under conditions highly favorable to oxidation, a similar modification can occur even in the absence of cells. In the present studies, oxidation of LDL simply by exposure to 5μMCu++ resulted in a modification that was indistinguishable from that produced by endothelial cells. Moreover, it was demonstrated that LDL oxidation by either method is accompanied by a marked decrease in amino group reactivity, comparable to that seen with the chemical modifications of LDL that lead to recognition by the acetyl LDL receptor. Inhibitors of proteolytic enzymes did not reduce fragmentation of apolipoprotein B during oxidation. The rate of cataboiism of intravenously injected oxidized LDL in guinea pigs was very rapid, and over 80% of the degradation occurred in the liver. These studies demonstrate that all of the changes associated with endothelial cell modification of LDL can be attributed to oxidation. The cells can, however, promote oxidation under conditions where it would otherwise occur very slowly. Modification of LDL by endothelial cells or 5 μM Cu++ results in a marked decrease in LDL amino group reactivity that correlates with accelerated LDL clearance via the acetyl LDL receptor and decreased clearance by the classical LDL receptor in cultured cells and in vivo.
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兔子白蛋白分解代谢的组织位点。
DOI：
10.1152/ajpendo.1983.244.1.e101
发表时间：
1983
期刊：
The American journal of physiology
影响因子：
--
作者：
Yedgar,S;Carew,TE;Pittman,RC;Beltz,WF;Steinberg,D
通讯作者：
Steinberg,D
影响因子：
6.5
作者：
R. Mahley;T. Innerarity;Michael S. Brown;Y. K. Ho;J. Goldstein
通讯作者：
R. Mahley;T. Innerarity;Michael S. Brown;Y. K. Ho;J. Goldstein
一种放射性碘标记的细胞内捕获配体，用于确定体内血浆蛋白降解的位点。
DOI：
10.1042/bj2120791
发表时间：
1983
期刊：
The Biochemical journal
影响因子：
--
作者：
Pittman,RC;Carew,TE;Glass,CK;Green,SR;TaylorJr,CA;Attie,AD
通讯作者：
Attie,AD
脂蛋白脂肪酶在巨噬细胞代谢富含甘油三酯的脂蛋白中的作用。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lindqvist,P;Ostlund-Lindqvist,AM;Witztum,JL;Steinberg,D;Little,JA
通讯作者：
Little,JA
DOI：
--
发表时间：
1981-05
期刊：
The American journal of pathology
影响因子：
--
作者：
R. Gerrity
通讯作者：
R. Gerrity