Assessment of the role of sphingosine 1-phosphate and its receptors in high-density lipoprotein-induced stimulation of astroglial cell function
Assessment of the role of sphingosine 1-phosphate and its receptors in high-density lipoprotein-induced stimulation of astroglial cell function
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DOI：
10.1042/bj20020867
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发表时间：
2003-03-15
影响因子：
4.1
通讯作者：
Okajima, F
中科院分区：
文献类型：
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作者：
Malchinkhuu, E;Sato, K;Okajima, F
有人提出，中枢神经系统中的脂蛋白参与调节一些独立于胆固醇代谢以及与脂质代谢相关的神经功能。我们最近证明脂蛋白是 I-磷酸鞘氨醇 (SIP) 的载体。这提出了SIP介导脂蛋白诱导的神经细胞功能的可能性。在当前的研究中，我们检查了血浆高密度脂蛋白（HDL）对星形胶质细胞功能的影响，特别关注脂蛋白相关的 SIP 的作用。在大鼠 I 型星形胶质细胞或 C6 神经胶质瘤细胞中，与 SIP 类似，HDL 刺激 DNA 合成和成纤维细胞生长因子-2 的 mRNA 表达，成纤维细胞生长因子-2 是一种有效的神经营养因子，与百日咳中细胞外信号调节激酶（ERK）的激活有关。毒素敏感方式。 HDL 分级分离研究的数据表明，SIP 可能是 ERK 激活的主要成分。在 C6 神经胶质瘤细胞中，HDL 还诱导磷脂酶 C 依赖性细胞内 Ca2+ 动员。用 SIP 使 C6 神经胶质瘤细胞脱敏，消除了这些 HDL 诱导的作用。此外，C6 神经胶质瘤细胞中 SIP 受体的过度表达导致 HDL 诱导的 ERK 激活和 Ca2+ 动员显着增强。因此，至少一些 HDL 诱导的作用可能是由星形胶质细胞中的细胞表面 SIP 受体介导的。这些结果表明，SIP 可能部分介导中枢神经系统中脂蛋白诱导的胆固醇代谢独立的神经细胞功能。
It has been suggested that lipoproteins in the central nervous system are involved in the regulation of several neural functions independent of cholesterol metabolism as well as those related to lipid metabolism. We recently demonstrated that lipoproteins are carriers for sphingosine I-phosphate (SIP). This raised the possibility that S I P mediates the neural cell functions induced by lipoproteins. In the current study, we examined the effects of plasma high-density lipoprotein (HDL) on astroglial cell functions, focusing especially on the role of the lipoprotein-associated S I P. In rat type I astrocytes or C6 glioma cells, similar to S I P, HDL stimulated DNA synthesis and mRNA expression of fibroblast growth factor-2, a potent neurotrophic factor, which was associated with the activation of extracellular signal-regulated kinase (ERK) in a pertussis toxin-sensitive manner. The data from fractionation studies of HDL indicated that S I P may be a major component for the activation of ERK. In C6 glioma cells, HDL also induced phospholipase C-dependent intracellular Ca2+ mobilization. Desensitization of the C6 glioma cells with SIP abolished these HDL-induced actions. Furthermore, overexpression of S I P receptors in C6 glioma cells led to a significant enhancement of HDL-induced ERK activation and Ca2+ mobilization. Thus, at least some HDL-induced actions may be mediated by cell-surface SIP receptors in astroglial cells. These results imply that SIP might partially mediate lipoprotein-induced cholesterol metabolism-independent neural cell functions in the central nervous system.