Acrolein is a product of lipid peroxidation reaction - Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins
Acrolein is a product of lipid peroxidation reaction - Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins
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DOI：
10.1074/jbc.273.26.16058
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发表时间：
1998-06-26
影响因子：
4.8
通讯作者：
Niki, E
中科院分区：
文献类型：
--
作者：
Uchida, K;Kanematsu, M;Niki, E
脂蛋白过氧化，尤其是载脂蛋白B-100的修饰，在动脉粥样硬化的发病机制中发挥着重要作用。然而，载脂蛋白在氧化过程中衍生化的化学机制还没有得到详细的研究。在本研究中，我们提供的证据表明，有毒污染物丙烯醛（CH_2 = CH-CHO）及其与赖氨酸残基的缀合物的形成参与了人低密度脂蛋白（LDL）的氧化修饰。为了确定蛋白质中丙烯醛-赖氨酸加合物的结构，进行了丙烯醛与赖氨酸衍生物的反应。使用N-α-乙酰赖氨酸，我们检测到一个单一的产品，这是一个新的丙烯醛-赖氨酸加合物，N-α-乙酰基-N-α-（3-甲酰基-3，4-脱氢哌啶子基）赖氨酸。加合物的酸水解导致可通过氨基酸分析检测的衍生物。结果表明，在体外孵育的LDL与丙烯醛，赖氨酸残基已经消失了部分恢复的N-α-（3-甲酰基-3，4-脱氢哌啶子基）赖氨酸。此外，我们发现，相同的衍生物中检测到的氧化修饰的LDL与Cu 2+和加合物的形成与LDL过氧化评估消耗的α-生育酚和胆固醇酯和伴随形成的胆固醇酯氢过氧化物。酶联免疫吸附试验，测量游离丙烯醛显示，相当数量的丙烯醛从铜+氧化的LDL释放。此外，金属催化氧化的花生四烯酸与丙烯醛的形成，表明多不饱和脂肪酸，包括花生四烯酸的LDL的过氧化过程中产生的丙烯醛的潜在来源。这些结果表明，丙烯醛不仅是一种污染物，而且是一种脂质过氧化产物，在生物系统中可能无处不在。
Lipoprotein peroxidation, especially the modification of apolipoprotein B-100, has been implicated to play an important role in the pathogenesis of atherosclerosis. However, there have been few detailed insights into the chemical mechanism of derivatization of apolipoproteins during oxidation, In the present study, we provide evidence that the formation of the toxic pollutant acrolein (CH2=CH-CHO) and its conjugate with lysine residues is involved in the oxidative modification of human low density lipoprotein (LDL), Upon incubation with LDL, acrolein preferentially reacted with lysine residues. To determine the structure of acrolein-lysine adduct in protein, the reaction of acrolein with a lysine derivative was carried out. Employing N-alpha-acetyllysine, we detected a single product, which was identified to be a novel acrolein-lysine adduct, N-alpha-acetyl-N-epsilon-(3-formyl-3,4-dehydropiperidino)lysine. The acid hydrolysis of the adduct led to the derivative that was detectable with amino acid analysis. It was revealed that, upon in vitro incubation of LDL with acrolein, the lysine residues that had disappeared were partially recovered by N-epsilon-(3-formyl-3,4-dehydropiperidino)lysine. In addition, we found that the same derivative was detected in the oxidatively modified LDL with Cu2+ and that the adduct formation was correlated with LDL peroxidation assessed by the consumption of alpha-tocopherol and cholesteryl ester and the concomitant formation of cholesteryl ester hydroperoxide. Enzyme-linked immunosorbent assay that measures free acrolein revealed that a considerable amount of acrolein was released from the Cu2+-oxidized LDL. Furthermore, metal-catalyzed oxidation of arachidonate was associated with the formation of acrolein, indicating that polyunsaturated fatty acids including arachidonate represent potential sources of acrolein generated during the peroxidation of LDL. These results indicate that acrolein is not just a pollutant but also a lipid peroxidation product that could be ubiquitously generated in biological systems.