Sato Koichi, Malchinkhuu Enkhzol, Horiuchi Yuta, Mogi Chihiro, Tomura Hideaki, Tosaka Masahiko, Yoshimoto Yuhei, Kuwabara Atsushi, Okajima Fumikazu
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
Biochem Biophys Res Commun. 2007 Aug 3;359(3):649-54. doi: 10.1016/j.bbrc.2007.05.131. Epub 2007 May 29.
High-density lipoprotein (HDL)-associated sphingosine 1-phosphate mediates a variety of lipoprotein-induced actions in vascular cell systems. However, it remains unknown whether extracellular S1P is associated with lipoproteins to exert biological actions in central nervous system. Human cerebrospinal fluid (CSF) induced rat astrocyte migration in a manner sensitive to S1P receptor antagonist VPC23019 and the migration activity was recovered in S1P fraction by thin-layer chromatography. Density-gradient separation of CSF revealed that the major S1P activity was detected in the HDL fraction. In conditioned medium of rat astrocytes cultured with sphingosine, the S1P activity was recovered again in the HDL fraction. The HDL fraction also induced migration of astrocytes and process retraction of oligodendrocytes in a manner similar to S1P. We concluded that S1P is accumulated in HDL-like lipoproteins in CSF and mediates some of lipoprotein-induced neural cell functions in central nervous system.
高密度脂蛋白（HDL）相关的1-磷酸鞘氨醇介导了血管细胞系统中多种脂蛋白诱导的作用。然而，细胞外1-磷酸鞘氨醇是否与脂蛋白相关以在中枢神经系统中发挥生物学作用仍不清楚。人脑脊液（CSF）以对1-磷酸鞘氨醇受体拮抗剂VPC23019敏感的方式诱导大鼠星形胶质细胞迁移，并且通过薄层色谱法在1-磷酸鞘氨醇组分中恢复了迁移活性。脑脊液的密度梯度分离显示，在HDL组分中检测到主要的1-磷酸鞘氨醇活性。在用鞘氨醇培养的大鼠星形胶质细胞的条件培养基中，HDL组分中再次恢复了1-磷酸鞘氨醇活性。HDL组分还以类似于1-磷酸鞘氨醇的方式诱导星形胶质细胞迁移和少突胶质细胞的突起回缩。我们得出结论，1-磷酸鞘氨醇在脑脊液中类似HDL的脂蛋白中积累，并介导中枢神经系统中一些脂蛋白诱导的神经细胞功能。
