DL-Homocysteine is a thiol-containing non-essential amino acid that acts a weak neurotoxin[1]. DL-Homocysteine has been widely used in both cell and animal models to regulate cardiovascular functions[2].
In vitro, DL-Homocysteine treatment at 100μM for 18 hours significantly induced adhesion of U937 cells without affecting the viability of cells[3]. Treatment with 50μM DL-Homocysteine for 8 hours significantly upregulated the expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in human aortic endothelial cells[4]. Exposure of rat neuronal cells to 100μM DL-Homocysteine for 6 days resulted in a significant decrease in cell viability and a large number of cell deaths[5]. Treatment with 500μM DL-Homocysteine for 24 hours significantly inhibited the proliferation of bovine aortic endothelial cells[6].
In vivo, DL-Homocysteine treatment via oral administration at 3g/kg/day for 5 months can counteract the inflammation caused by cholesterol in male Sprague Dawley rats and improve the spatial learning ability[7]. A single intraperitoneal injection of 1.3mmol/kg of DL-Homocysteine for 60 minutes can significantly promote the production of kynurenic acid (KYNA) in the male Wistar rats' bodies[8].
References:
[1] Bleich S, Degner D, Sperling W, et al. Homocysteine as a neurotoxin in chronic alcoholism[J]. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2004, 28(3): 453-464.
[2] Stühlinger M C, Tsao P S, Her J H, et al. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine[J]. Circulation, 2001, 104(21): 2569-2575.
[3] Silverman M D, Tumuluri R J, Davis M, et al. Homocysteine upregulates vascular cell adhesion molecule-1 expression in cultured human aortic endothelial cells and enhances monocyte adhesion[J]. Arteriosclerosis, thrombosis, and vascular biology, 2002, 22(4): 587-592.
[4] Poddar R, Sivasubramanian N, DiBello P M, et al. Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease[J]. Circulation, 2001, 103(22): 2717-2723.
[5] Lipton S A, Kim W K, Choi Y B, et al. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor[J]. Proceedings of the National Academy of Sciences, 1997, 94(11): 5923-5928.
[6] Wejksza K, Rzeski W, Turski W A. Kynurenic acid protects against the homocysteine-induced impairment of endothelial cells[J]. Pharmacological Reports, 2009, 61(4): 751-756.
[7] Pirchl M, Ullrich C, Sperner-Unterweger B, et al. Homocysteine has anti-inflammatory properties in a hypercholesterolemic rat model in vivo[J]. Molecular and Cellular Neuroscience, 2012, 49(4): 456-463.
[8] Luchowska E, Luchowski P, Paczek R, et al. Dual effect of DL‐homocysteine and S‐adenosylhomocysteine on brain synthesis of the glutamate receptor antagonist, kynurenic acid[J]. Journal of neuroscience research, 2005, 79(3): 375-382.
DL-Homocysteine是一种含硫非必需氨基酸，具有弱神经毒性[1]。DL-Homocysteine已广泛应用于细胞和动物模型的心血管功能调控研究[2]。
在体外，100μM 的DL-Homocysteine处理U937细胞18小时可显著诱导细胞黏附且不影响细胞活力[3]。50μM的DL-Homocysteine处理人主动脉内皮细胞8小时能显著上调单核细胞趋化蛋白-1（MCP-1）和白细胞介素-8（IL-8）表达[4]。100μM的DL-Homocysteine处理大鼠神经元细胞6天会导致细胞活力显著下降并引发大量细胞死亡[5]。500μM的DL-Homocysteine处理牛主动脉内皮细胞24小时可显著抑制细胞增殖[6]。
在体内，雄性Sprague Dawley大鼠每日口服DL-Homocysteine（3g/kg；持续5个月）可拮抗胆固醇引起的炎症并改善空间学习能力[7]。雄性Wistar大鼠单次腹腔注射1.3mmol/kg的DL-Homocysteine（60分钟）能显著促进体内犬尿喹啉酸（KYNA）生成[8]。