Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Atherosclerosis. 2013 Jul;229(1):102-9. doi: 10.1016/j.atherosclerosis.2013.04.024. Epub 2013 Apr 28.
Sphingosine 1-phosphate (S1P) is a vasoprotective lipid mediator that is mainly carried on HDL in the circulation and several anti-atherosclerotic properties of HDL is considered to be ascribed to S1P. Since S1P riding on HDL was recently shown to bind to apolipoprotein M (apoM), which is derived from liver, we analyzed the possible involvement of liver in S1P metabolism.
Using adenoviruses, we overexpressed apoM in HepG2 cells and mice livers and found that both the medium/plasma and cell/liver S1P contents increased. Among lipoprotein subclasses, S1P contents increased mainly in HDL fractions. On the other hand, hepatectomy resulted in the reduction of plasma S1P levels in mice. The incubation of S1P in the conditional medium of apoM-overexpressing HepG2 cells interfered with S1P degradation. Furthermore, adenoviral hepatic overexpression of apoM resulted in increase in the S1P level of plasma but not of blood cells, while combination of hepatic apoM overexpression and intraperitoneal administration of C₁₇-sphingosine resulted in the increase in the C₁₇-S1P level both in livers and in plasma, but again not in blood cells.
Livers are involved in S1P dynamism, and it was suggested that apoM, produced from livers, increases circulating plasma S1P by augmenting the S1P output from livers and modifies extracellular S1P metabolism.
鞘氨醇 1-磷酸（S1P）是一种血管保护性脂质介质，主要在循环中与高密度脂蛋白（HDL）结合，而 HDL 的几种抗动脉粥样硬化特性被认为归因于 S1P。由于最近发现 S1P 与载脂蛋白 M（apoM）结合，而 apoM 来源于肝脏，因此我们分析了肝脏在 S1P 代谢中的可能作用。
我们使用腺病毒在 HepG2 细胞和小鼠肝脏中过表达 apoM，发现细胞/肝脏和中/血浆 S1P 含量均增加。在脂蛋白亚类中，S1P 含量主要在 HDL 部分增加。另一方面，肝切除术导致小鼠血浆 S1P 水平降低。将 S1P 孵育在 apoM 过表达 HepG2 细胞的条件培养基中会干扰 S1P 的降解。此外，apoM 在肝脏中的过表达会增加血浆中的 S1P 水平，但不会增加血细胞中的 S1P 水平，而同时进行肝脏 apoM 过表达和腹腔内给予 C₁₇-鞘氨醇会导致肝脏和血浆中的 C₁₇-S1P 水平增加，但不会增加血细胞中的 C₁₇-S1P 水平。
肝脏参与 S1P 动力学，提示肝脏产生的 apoM 通过增加肝脏的 S1P 输出和改变细胞外 S1P 代谢来增加循环血浆 S1P。
