ANTIOXIDANT POTENTIAL OF HOMOCYSTAMIDE LDL ADDUCT

同型半胱氨酸硫内酯是一种环状硫代酯 在动脉粥样硬化形成中。这种分子很容易将伯胺酰化， 形成高甲酰胺加合物，其包含伯胺和 硫醇。在这里，我们对抗氧化剂进行了表征和评估 同型半胱胺-低密度脂蛋白加合物的潜力，a 同型半胱氨酸硫内酯与硫内酯的酰化反应产物 低密度脂蛋白。同型半胱氨酸硫内酯治疗低密度脂蛋白可导致 与低密度脂蛋白结合的硫醇含量随时间增加，达到 75分钟时，约为250nmoL硫醇/mg低密度脂蛋白。这个 随着低密度脂蛋白硫醇含量的增加，低密度脂蛋白在 75分钟。低密度脂蛋白结合的硫醇的增加是可逆的 使用硫醇封闭自旋标签甲硫磺酸盐进行治疗。 通过电子自旋共振(ESR)自旋标记进行了评估 技术中，高半胱胺加合物主要暴露于 低密度脂蛋白的水相，由明显的ESR谱显示 用亲水性顺磁性松弛剂铬进行展宽 草酸盐。相对电泳迁移率 与天然低密度脂蛋白相比，同型半胱胺-低密度脂蛋白加合物增加。 同型半胱氨酸硫代内酯处理的伯氨基浓度 低密度脂蛋白与天然低密度脂蛋白无显著差异(p&lt；0.05)。这个 同型半胱胺-低密度脂蛋白加合物对铜(2+)-和2，2‘-偶氮苯的抗性 (2-氨基丙烷)介导的氧化(相对于天然低密度脂蛋白) 通过硫代巴比妥酸活性物质的形成和 维生素E的耗竭用N-乙基马来酰胺封闭硫醇 阻止同型半胱胺-低密度脂蛋白加合物的抗氧化作用。这个 同型半胱胺-低密度脂蛋白加合物与低密度脂蛋白的关系 对动脉粥样硬化的研究进展进行了讨论。

Homocysteine thiolactone is a cyclic thioester that is implicated in atherogenesis. This molecule will readily acylate primary amines, forming a homocystamide adduct, which contains a primary amine and a thiol. Here, we have characterized and evaluated the antioxidant potential of the homocystamide-low-density lipoprotein (LDL) adduct, a product of the acylation reaction between homocysteine thiolactone and LDL. Treatment of LDL with homocysteine thiolactone resulted in a time-dependent increase in LDL-bound thiol content that reached approximately 250 nmol thiol/mg LDL protein at 75 minutes. The increase in LDL thiol content was followed by aggregation of LDL after 75 minutes. The increase in LDL-bound thiols was reversible by treatment with the thiol blockersing spin label, methanethiosulfonate. As assessed by the electron spin resonance (ESR) spin labeling technique, the homocystamide adducts were predominately exposed to the aqueous phase of LDL, shown by the sharp ESR spectra that were greatly broadened by the hydrophillic paramagnetic relaxing agent, chromium oxalate. The relative electrophoretic mobility of the homocystamide-LDL adduct was increased with respect to native LDL. Primary amino group concentration of homocysteine thiolactone-treated LDL was not significantly different than native LDL (p < 0.05). The homocystamide-LDL adduct was resistant to Cu(2+)- and 2,2'-azobis (2-amidinopropane)- mediated oxidation (with respect to native LDL) as measured by the formation of thiobarbituric reactive substances and the depletion of vitamin E. Blocking thiols with N-ethylmaleamide prevented the antioxidant effect of the homocystamide-LDL adduct. The potential relationship between the homocystamide-LDL adduct and the development of atherosclerosis is discussed.