Homocysteine thiolactone and protein homocysteinylation in human endothelial cells - Implications for atherosclerosis
Homocysteine thiolactone and protein homocysteinylation in human endothelial cells - Implications for atherosclerosis
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DOI：
10.1161/01.res.87.1.45
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发表时间：
2000-07-07
影响因子：
20.1
通讯作者：
Aviv, A
中科院分区：
文献类型：
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作者：
Jakubowski, H;Zhang, L;Aviv, A
某些氨酰-tRNA合成酶对非蛋白质氨基酸同型半胱氨酸的编辑导致硫酯同型半胱氨酸硫内酯的形成。在这里，我们表明，在存在的同型半胱氨酸，蛋氨酸和叶酸的生理浓度，人脐静脉内皮细胞有效地转换同型半胱氨酸硫内酯。这种转化的程度与同型半胱氨酸浓度成正比，与甲硫氨酸浓度成反比，表明甲硫氨酰-tRNA合成酶的参与。叶酸通过降低内皮细胞中的同型半胱氨酸和增加蛋氨酸浓度来抑制硫内酯的合成。我们还表明，在内皮细胞培养物中，蛋白质翻译后同型半胱氨酸化的程度随着同型半胱氨酸水平的增加而增加，但随着叶酸和HDL水平的增加而减少。这些数据支持了一个假设，即同型半胱氨酸代谢转化为硫内酯和蛋白质同型半胱氨酸化硫内酯可能发挥作用，同型半胱氨酸诱导的血管损伤。
Editing of the nonprotein amino acid homocysteine by certain aminoacyl-tRNA synthetases results in the formation of the thioester homocysteine thiolactone. Here we show that in the presence of physiological concentrations of homocysteine, methionine, and folic acid, human umbilical vein endothelial cells efficiently convert homocysteine to thiolactone. The extent of this conversion is directly proportional to homocysteine concentration and inversely proportional to methionine concentration, suggesting involvement of methionyl-tRNA synthetase. Folic acid inhibits the synthesis of thiolactone by lowering homocysteine and increasing methionine concentrations in endothelial cells. We also show that the extent of post-translational protein homocysteinylation increases with increasing homocysteine levels but decreases with increasing folic acid and HDL levels in endothelial cell cultures. These data support a hypothesis that metabolic conversion of homocysteine to thiolactone and protein homocysteinylation by thiolactone may play a role in homocysteine-induced vascular damage.