Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions
Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions
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DOI：
10.1042/0264-6021:3520809
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发表时间：
2000-12-15
影响因子：
4.1
通讯作者：
Okajima, F
中科院分区：
文献类型：
--
作者：
Murata, N;Sato, K;Okajima, F
血浆或血清中 1-磷酸鞘氨醇 (S1P) 的浓度远高于刺激其受体所需的鞘脂的半最大浓度。然而，Edg-.3（在中国仓鼠卵巢细胞中过度表达的 S1P 受体之一）介导的肌醇磷酸盐对血浆或血清的反应远小于这些样品中 S1P 总量的预期反应。在木炭处理的低 S1P 血清存在下，磷酸肌醇对外源性 S1P 的反应显着减弱。煮沸会使抑制作用消失，但血清透析不会消失。血清的抑制作用是针对 S1P 的，并且与外源性 S1P 的捕获有关；木炭处理的血清在一定程度上增强了磷酸肌醇对 P-2-嘌呤能激动剂的反应。在血浆或血清的成分中，脂蛋白如低密度脂蛋白和高密度脂蛋白表现出比脂蛋白缺乏的血清更强的捕获S1P的活性。与这一观察结果一致，我们检测到脂蛋白中每单位蛋白量的 S1P 含量比脂蛋白缺乏血清中高 15-100 倍。因此，尽管脂蛋白级分的蛋白质含量仅占血浆或血清总蛋白质含量的4%，但超过60%的S1P分布在该级分中。这些结果表明，S1P 与血清或血浆成分（包括脂蛋白）的紧密结合可能会干扰 S1P 与其受体的结合，从而减弱细胞中脂质受体介导的作用。
The concentration of sphingosine 1-phosphate (S1P) in plasma or serum is much higher than the half-maximal concentration of the sphingolipid needed to stimulate its receptors. Nevertheless, the inositol phosphate response to plasma or serum mediated by Edg-.3, one of the S1P receptors, which was overexpressed in Chinese hamster ovary cells, was much smaller than the response expected from the total amount of S1P in these samples. The inositol phosphate response to exogenous S1P was markedly attenuated in the presence of charcoal-treated low-S1P serum. The inhibitory effect was lost by boiling but not by dialysis of the serum. The inhibitory action of the serum was specific to S1P and was associated with the trapping of exogenous S1P; the inositol phosphate response to P-2-purinergic agonists was somewhat enhanced by the charcoal-treated serum. Among the components of plasma or serum, lipoproteins such as low-density and high-density lipoproteins showed a stronger activity for trapping S1P than lipoprotein-deficient serum. Consistent with this observation, we detected a 15-100-fold higher amount of S1P per unit amount of protein in lipoproteins than in the lipoprotein-deficient serum. Thus even though the protein content of the lipoprotein fraction contributes to only 4% of the total protein content of plasma or serum, more than 60% of S1P is distributed in this fraction. These results suggest that the tight binding of S1P to the components of serum or plasma, including lipoproteins, may interfere with the S1P binding to its receptors and thereby attenuate the lipid-receptor-mediated actions in the cells.