Hirano K, Ogihara T, Miki M, Yasuda H, Tamai H, Kawamura N, Mino M
Department of Pediatrics, Osaka Medical College, Japan.
Free Radic Res. 1994 Oct;21(5):267-76. doi: 10.3109/10715769409056579.
Homocystinuria is an inborn error of methionine metabolism that is characterized by the premature development of arteriosclerosis. As one of the major factors in the pathogenesis of arteriosclerosis, modification of low-density lipoprotein (LDL) has received widespread attention by many investigators. In this study, to elucidate the relationship between elevated homocysteine levels and premature arteriosclerosis, we investigated the role of homocysteine in the iron-catalyzed oxidative modification of LDL. When LDL isolated from a healthy subject was incubated with homocysteine and ferric ion, a gradual decrease of polyunsaturated fatty acids (PUFA), formation of thiobarbituric acid-reactive substances (TBARS) and fluorescent substances, and the fragmentation of apoprotein B (apoB) were observed. The extent of oxidative modification was dependent on the concentration of homocysteine. Modification of LDL was suppressed until the remaining alpha-tocopherol concentration reached a critical level. When the alpha-tocopherol content of LDL was increased by 2.6-fold, both the formation of TBARS and the fragmentation of apoB were suppressed. These results suggest that homocysteine might promote iron-catalyzed oxidation of LDL and imply its role for the development of premature arteriosclerosis.
同型胱氨酸尿症是一种甲硫氨酸代谢的先天性缺陷，其特征为动脉硬化过早发展。作为动脉硬化发病机制的主要因素之一，低密度脂蛋白（LDL）的修饰受到了众多研究者的广泛关注。在本研究中，为阐明同型半胱氨酸水平升高与过早动脉硬化之间的关系，我们研究了同型半胱氨酸在铁催化的LDL氧化修饰中的作用。当从健康受试者分离的LDL与同型半胱氨酸和铁离子一起孵育时，观察到多不饱和脂肪酸（PUFA）逐渐减少、硫代巴比妥酸反应性物质（TBARS）和荧光物质形成以及载脂蛋白B（apoB）片段化。氧化修饰的程度取决于同型半胱氨酸的浓度。直到剩余的α-生育酚浓度达到临界水平，LDL的修饰才受到抑制。当LDL的α-生育酚含量增加2.6倍时，TBARS的形成和apoB的片段化均受到抑制。这些结果表明，同型半胱氨酸可能促进铁催化的LDL氧化，并暗示其在过早动脉硬化发展中的作用。
