LIPID ADVANCED GLYCOSYLATION - PATHWAY FOR LIPID OXIDATION IN-VIVO
LIPID ADVANCED GLYCOSYLATION - PATHWAY FOR LIPID OXIDATION IN-VIVO
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DOI：
10.1073/pnas.90.14.6434
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发表时间：
1993-07-15
影响因子：
11.1
通讯作者：
VLASSARA, H
中科院分区：
文献类型：
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作者：
BUCALA, R;MAKITA, Z;VLASSARA, H
为了研究体内脂质氧化修饰的潜在机制，我们研究了磷脂与葡萄糖直接反应形成晚期糖基化终产物（AGEs）的可能性，这些终产物随后引发脂质氧化。磷脂连接的AGEs在体外很容易形成，模仿了蛋白质糖基化晚期产生的AGEs的吸光度、荧光和免疫化学特性。不饱和脂肪酸残基的氧化，通过反应性醛的形成来评估，其发生的速率与脂质晚期糖基化的速率相似。氨基胍，一种阻止蛋白质晚期糖基化的药物，同时抑制脂质晚期糖基化和氧化修饰。低密度脂蛋白（LDL）与葡萄糖孵育产生AGE片段，这些片段同时附着在脂质和载脂蛋白组分上。氧化LDL与age修饰LDL同时形成。具有重要意义的是，对糖尿病患者LDL样本的AGE ELISA分析显示，与正常非糖尿病对照组样本相比，载脂蛋白和脂质相关的AGEs水平均有所增加。糖尿病患者循环中氧化LDL水平升高，且与脂质AGE水平显著相关。这些数据支持了AGE氧化在体内启动脂质氧化中起重要且可能是主要作用的概念。
To address potential mechanisms for oxidative modification of lipids in vivo, we investigated the possibility that phospholipids react directly with glucose to form advanced glycosylation end products (AGEs) that then initiate lipid oxidation. Phospholipid-linked AGEs formed readily in vitro, mimicking the absorbance, fluorescence, and immunochemical properties of AGEs that result from advanced glycosylation of proteins. Oxidation of unsaturated fatty acid residues, as assessed by reactive aldehyde formation, occurred at a rate that paralleled the rate of lipid advanced glycosylation. Aminoguanidine, an agent that prevents protein advanced glycosylation, inhibited both lipid advanced glycosylation and oxidative modification. Incubation of low density lipoprotein (LDL) with glucose produced AGE moieties that were attached to both the lipid and the apoprotein components. Oxidized LDL formed concomitantly with AGE-modified LDL. Of significance, AGE ELISA analysis of LDL specimens isolated from diabetic individuals revealed increased levels of both apoprotein- and lipid-linked AGEs when compared to specimens obtained from normal, nondiabetic controls. Circulating levels of oxidized LDL were elevated in diabetic patients and correlated significantly with lipid AGE levels. These data support the concept that AGE oxidation plays an important and perhaps primary role in initiating lipid oxidation in vivo.