L-Homocysteine is a sulfur-containing amino acid, which is an intermediate metabolite of an essential amino acid, methionine (Met)[1]. L-Homocysteine has been utilized in research aimed at regulating the functions of the nervous system and the cardiovascular system[2].
In vitro, L-Homocysteine treatment at 2000μM for 48 hours inhibited the cell viability of human umbilical vein endothelial cells (HUVECs) and significantly increased the expression of cathepsin V[3]. Treatment with 50μM L-Homocysteine for 3 hours can promote the massive release of monocyte chemoattractant protein-1 and IL-8 proteins in human aortic endothelial cells (HAECs)[4]. Treatment with 500μM L-Homocysteine for 24 hours led to an increase in the protein expression of matrix metalloproteinase-9 (MMP-9) in Raw 264.7 cells, and the expression of CD40 was significantly decreased, accompanied by increased reactive oxygen species (ROS) production[5]. In the cultured rat mesangial cells, treatment with L-Homocysteine (160μM) for 48 hours significantly increased the mRNA levels of TIMP-1 and Gp91, and led to the deposition of type I collagen, accompanied by cell proliferation and enhanced NADH oxidase activity[6].
In vivo, L-Homocysteine treatment via oral administration (2g/L, dissolved in drinking water) for 16 weeks led to an increase in fasting blood glucose levels in mice, resulting in insulin resistance in mice[7]. After oral administration of water containing L-Homocysteine (1.8g/L) for four weeks, the expression of β-catenin and mitochondrial autophagy-related proteins decreased in the myocardium of mouse, and cardiac hypertrophy occurred[8].
References:
[1] Nakao A, Suzuki H, Ueno H, et al. Discovery and structural analyses of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs[J]. Bioorganic & Medicinal Chemistry, 2015, 23(15): 4952-4969.
[2] Moretti R, Caruso P. The controversial role of homocysteine in neurology: from labs to clinical practice[J]. International journal of molecular sciences, 2019, 20(1): 231.
[3] Leng Y P, Ma Y S, Li X G, et al. l‐Homocysteine‐induced cathepsin V mediates the vascular endothelial inflammation in hyperhomocysteinaemia[J]. British journal of pharmacology, 2018, 175(8): 1157-1172.
[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] Winchester L J, Veeranki S, Givvimani S, et al. Homocysteine elicits an M1 phenotype in murine macrophages through an EMMPRIN-mediated pathway[J]. Canadian journal of physiology and pharmacology, 2015, 93(7): 577-584.
[6] Yang Z Z, Zou A P. Homocysteine enhances TIMP-1 expression and cell proliferation associated with NADH oxidase in rat mesangial cells[J]. Kidney international, 2003, 63(3): 1012-1020.
[7] Zhang X, Qu Y Y, Liu L, et al. Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation[J]. Cell Reports, 2021, 37(2).
[8] Lei Y, Hu H, Tang H, et al. Homocysteine promotes cardiomyocyte hypertrophy through inhibiting β-catenin/FUNDC1 mediated mitophagy[J]. Scientific Reports, 2025, 15(1): 22207.
L-Homocysteine是一种含硫氨基酸，作为必需氨基酸蛋氨酸（Met）的中间代谢产物存在[1]。L-Homocysteine被广泛应用于神经系统和心血管系统功能调控的研究[2]。
在体外，2000μM的L-Homocysteine处理48小时可抑制人脐静脉内皮细胞（HUVECs）活力并显著增加组织蛋白酶V表达[3]。50μM的L-Homocysteine处理3小时能促进人主动脉内皮细胞（HAECs）大量释放单核细胞趋化蛋白-1和IL-8[4]。500μM的L-Homocysteine处理Raw 264.7细胞24小时会导致基质金属蛋白酶-9（MMP-9）蛋白表达增加，CD40表达显著降低，并伴随活性氧（ROS）生成增加[5]。160μM的L-Homocysteine处理培养的大鼠系膜细胞48小时可显著升高TIMP-1和Gp91的mRNA水平，导致I型胶原沉积，并伴随细胞增殖和NADH氧化酶活性增强[6]。
在体内，小鼠通过饮用水摄入L-Homocysteine（2g/L；持续16周）后，空腹血糖水平升高并出现胰岛素抵抗[7]。饮用含L-Homocysteine（1.8g/L）的水持续4周的小鼠心肌中β-连环蛋白和线粒体自噬相关蛋白表达下降，并导致小鼠心脏肥大[8]。