Książek Monika, Baranowska Urszula, Chabowski Adrian, Baranowski Marcin
Department of Physiology, Medical University of Białystok, Białystok, Poland.
Department of Pharmacology Medical University of Białystok, Białystok, Poland.
Cell Physiol Biochem. 2018;45(1):67-77. doi: 10.1159/000486223. Epub 2017 Dec 22.
BACKGROUND/AIMS: Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in high concentration in plasma. The majority of plasma S1P is transported bound to HDL and albumin. Although the major sources of circulating S1P have been identified, it remains obscure what is the contribution of different organs/tissues to S1P homeostasis in plasma. Answering this question was the major aim of the present study.
The experiment was performed on male Wistar rats from whom blood samples were taken from either: 1) femoral vein, right ventricle of the heart, and abdominal aorta (n=15) or 2) hepatic vein, portal vein, and abdominal aorta (n=11). Plasma was fractionated by sequential flotation ultracentrifugation and sphingolipids were quantified by a HPLC method.
Compared to the mixed venous blood sampled from the right ventricle, total plasma and lipoprotein-depleted plasma (LPDP) concentration of S1P in the arterial blood was lower. On the other hand, the level of S1P increased across the leg both in plasma and LPDP. The concentration of S1P, sphingosine, and sphinganine in the plasma, HDL, and LPDP isolated from the blood taken from the hepatic vein was markedly higher compared to both arterial and portal blood.
We conclude that, in contrast to HDL-bound S1P, albumin-associated S1P is very labile in the circulation. It is degraded in the pulmonary, and to a lesser extent, gastrointestinal circulation, and released across the liver and skeletal muscle. We also conclude that liver is an important source of HDL-bound S1P and circulating free sphingoid bases.
背景/目的：鞘氨醇-1-磷酸（S1P）是一种生物活性溶血鞘脂，在血浆中浓度较高。血浆中的大部分S1P与高密度脂蛋白（HDL）和白蛋白结合运输。虽然已确定循环S1P的主要来源，但不同器官/组织对血浆中S1P稳态的贡献仍不清楚。回答这个问题是本研究的主要目的。
对雄性Wistar大鼠进行实验，从以下部位采集血样：1）股静脉、心脏右心室和腹主动脉（n = 15）或2）肝静脉、门静脉和腹主动脉（n = 11）。通过连续浮选超速离心法对血浆进行分级分离，并用高效液相色谱法对鞘脂进行定量。
与从右心室采集的混合静脉血相比，动脉血中S1P的总血浆浓度和无脂蛋白血浆（LPDP）浓度较低。另一方面，腿部血浆和LPDP中的S1P水平均升高。从肝静脉采集的血液中分离出的血浆、HDL和LPDP中的S1P、鞘氨醇和二氢鞘氨醇浓度明显高于动脉血和门静脉血。
我们得出结论，与HDL结合的S1P不同，与白蛋白结合的S1P在循环中非常不稳定。它在肺部降解，在胃肠道循环中降解程度较小，并通过肝脏和骨骼肌释放。我们还得出结论，肝脏是HDL结合的S1P和循环游离鞘氨醇碱基的重要来源。
