Possible involvement of sphingomyelin in the regulation of the plasma sphingosine 1-phosphate level in human subjects
Possible involvement of sphingomyelin in the regulation of the plasma sphingosine 1-phosphate level in human subjects
复制标题
鞘磷脂可能参与人类受试者血浆 1-磷酸鞘氨醇水平的调节
DOI：
10.1016/j.clinbiochem.2015.03.019
复制
发表时间：
2015
影响因子：
2.8
通讯作者：
Yatomi Y
中科院分区：
文献类型：
--
作者：
Ohkawa R;Kurano M;Mishima Y;Nojiri T;Tokuhara Y;Kishimoto T;Nakamura K;Okubo S;Hosogaya S;Ozaki Y;Yokota H;Igarashi K;Ikeda H;Tozuka M;Yatomi Y
目的：鞘磷脂1-磷酸（S1P）是一种具有生物活性的鞘脂介质。尽管血浆S1P浓度据报道是由细胞成分决定的，包括红细胞、血小板和血管内皮细胞，但其他因素如血清鞘磷脂（SM）和autotaxin （ATX）的可能参与仍有待阐明。设计与方法：采用高效液相色谱法测定S1P，采用酶促法测定SM和溶血磷脂酸（LPA），采用双位点酶免疫法测定ATX抗原，采用溶血磷脂酶D活性法测定ATX活性。为了分离脂蛋白，血浆样品采用快速蛋白液相色谱（FPLC），利用Superose 6柱进行分离。结果血浆S1P水平与SM、溶血磷脂酰胆碱水平呈正相关，与磷脂酰胆碱水平无显著相关性。虽然SM存在于极低密度脂蛋白（VLDL）部分，但血浆S1P水平和SM水平不受饲喂的影响。血浆S1P水平与ATX活性呈负相关。虽然100 μmol/L鞘氨酰磷胆碱（SPC）与血清孵育后由于ATX的存在导致S1P水平显著升高，但SPC的生理浓度没有类似的作用。结论血浆S1P水平受血清SM水平的影响，而ATX参与血浆S1P水平升高的可能性至少在健康人中是很小的。
ObjectivesSphingosine 1-phosphate (S1P) is a bioactive sphingolipid mediator. Although the plasma S1P concentration is reportedly determined by cellular components, including erythrocytes, platelets, and vascular endothelial cells, the possible involvement of other factors, such as serum sphingomyelin (SM) and autotaxin (ATX), remains to be elucidated.Design and methodsWe measured S1P using high-performance liquid chromatography (HPLC), SM and lysophosphatidic acid (LPA) using enzymatic assays, ATX antigen using a two-site enzyme immunoassay, and ATX activity using a lysophospholipase D activity assay. To fractionate the lipoproteins, plasma samples were separated using fast protein liquid chromatography (FPLC) utilizing a Superose 6 column.ResultsThe plasma S1P level was positively correlated with the levels of SM and lysophosphatidylcholine, but not with the level of phosphatidylcholine. Although SM was present in the very low-density lipoprotein (VLDL) fraction, neither the plasma S1P level nor the SM level was affected by feeding. The plasma S1P level was negatively correlated with the ATX activity. Although the incubation of 100 μmol/L of sphingosylphosphorylcholine (SPC) with the serum resulted in a significant increase in the S1P level because of the presence of ATX, the physiological concentration of SPC did not mimic this effect.ConclusionThe plasma S1P level was affected by the serum SM level, while the possibility of ATX involvement in the increase in the plasma S1P level was considered to be remote at least in healthy human subjects.