Department of Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Department of Laboratory Medicine, the Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Curr Mol Med. 2019;19(2):120-126. doi: 10.2174/1566524019666190308115624.
Homocysteine (Hcy) has been suggested as an independent risk factor for atherosclerosis. Apolipoprotein M (apoM) is a constituent of the HDL particles. The goal of this study was to examine the serum levels of homocysteine and apoM and to determine whether homocysteine influences apoM synthesis.
Serum levels of apoM and Hcy in 17 hyperhomocysteinemia (HHcy) patients and 19 controls were measured and their correlations were analyzed. Different concentrations of homocysteine (Hcy) and LY294002, a specific phosphoinositide 3- kinase (PI3K) inhibitor, were used to treat HepG2 cells. The mRNA levels were determined by RT-PCR and the apoM protein mass was measured by western blot.
We found that decreased serum apoM levels corresponded with serum HDL levels in HHcy patients, while the serum apoM levels showed a statistically significant negative correlation with the serum Hcy levels. Moreover, apoM mRNA and protein levels were significantly decreased after the administration of Hcy in HepG2 cells, and this effect could be abolished by addition of LY294002.
Present study demonstrates that Hcy downregulates the expression of apoM by mechanisms involving the PI3K signal pathway.
同型半胱氨酸(Hcy)已被认为是动脉粥样硬化的独立危险因素。载脂蛋白 M(apoM)是 HDL 颗粒的组成部分。本研究的目的是检测血清同型半胱氨酸和载脂蛋白 M 的水平,并确定同型半胱氨酸是否影响载脂蛋白 M 的合成。
测定 17 例高同型半胱氨酸血症(HHcy)患者和 19 例对照者的血清 apoM 和 Hcy 水平,并分析其相关性。用不同浓度的同型半胱氨酸(Hcy)和 LY294002,一种特异性磷脂酰肌醇 3-激酶(PI3K)抑制剂,处理 HepG2 细胞。用 RT-PCR 测定 apoM mRNA 水平,用 Western blot 测定 apoM 蛋白质量。
我们发现 HHcy 患者血清 apoM 水平与血清 HDL 水平呈负相关,而血清 apoM 水平与血清 Hcy 水平呈显著负相关。此外,Hcy 处理 HepG2 细胞后,apoM mRNA 和蛋白水平显著降低,加入 LY294002 可消除这种作用。
本研究表明,Hcy 通过涉及 PI3K 信号通路的机制下调 apoM 的表达。