Sphingosine 1-phosphate (S1P) induces shape change in rat C6 glioma cells through the S1P2 receptor:: development of an agonist for S1P receptors
Sphingosine 1-phosphate (S1P) induces shape change in rat C6 glioma cells through the S1P2 receptor:: development of an agonist for S1P receptors
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DOI：
10.1211/jpp.59.7.0017
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发表时间：
2007-07-01
影响因子：
3.3
通讯作者：
Im, Dong-Soon
中科院分区：
文献类型：
--
作者：
Kim, Kyeok;Kim, Yu-Lee;Im, Dong-Soon
异丙肾上腺素治疗导致大鼠C6胶质瘤细胞形态的改变。这种形态变化通过加入鞘氨醇1-磷酸（S1P）而恢复。利用这种形态变化作为反应标记，我们确定DS-SG-44 (（2.5,3R)-2-氨基-3羟基-4-（4-辛基苯基）丁基磷酸）是SlP受体的激动剂。与ds - sg -44结构相关的分子如DS-SG-45 (（2S,3R)-2-氨基-3-羟基-4-（3-辛基苯基）丁基磷酸）和DS-SG-12 (（2S,3R)2-氨基-4-（4-辛基苯基）丁烷-1,3-二醇）未观察到ds - sg -44诱导的形态逆转。S1P-和ds - sg -44诱导的形状变化既不能被S1P(1)/S1P(3)受体激动剂VPC24191复制，也不能被S1P(1)/S1P(3)受体拮抗剂VPC230119抑制。S1P(2)受体小干扰RNA （siRNA）转染极大地抑制了ds - sg -44诱导的形状变化，部分抑制了slp诱导的反应。在VPC23019存在的情况下，siRNA转染S1P(2)受体几乎完全阻断了S1P-和ds - sg -44诱导的形状变化。结果表明，新合成的S1P类似物DS-SG-44具有S1P受体激动剂的作用，S1P诱导的大鼠C6胶质瘤细胞形状变化主要通过S1P(2)受体介导，并通过S1P(1)/S1P(3)受体协同介导。
Treatment with isoprenaline led to a change in the cell morphology of rat C6 glioma cells. This morphological change was reverted by the addition of sphingosine 1-phosphate (S1P). Using this morphological change as a response marker we determined that DS-SG-44 ((2.5,3R)-2-amino-3hydroxy-4-(4-octylphenyl)butyl phosphoric acid) was an agonist of SlP receptors. The DS-SG-44-induced morphological reversion was not observed with such structurally related molecules as DS-SG-45 ((2S,3R)-2-amino-3-hydroxy-4-(3-octylphenyl)butyl phosphoric acid) and DS-SG-12 ((2S,3R)2-amino-4-(4-octylphenyl)butane-1,3-diol). The S1P- and DS-SG-44-induced shape changes were nseither reproduced with the S1P(1)/S1P(3) receptor agonist VPC24191 nor inhibited by the S1P(1)/S1P(3) receptor antagonist, VPC230119. Transfection with small interfering RNA (siRNA) for the S1P(2) receptor greatly inhibited the DS-SG-44-induced shape change, and in part an SlP-induced response. In the presence of VPC23019, siRNA transfection for the S1P(2) receptor almost completely blocked the S1P- and DS-SG-44-induced shape changes. Our results suggested that DS-SG-44, a newly-synthesized S1P analogue, acted as an S1 P receptor agonist and that the S1P-induced shape change in rat C6 glioma cells was mediated mainly through the S1P(2) receptor, and cooperatively through the S1P(1)/S1P(3) receptors.