Enhancement of intracellular sphingosine-1-phosphate production by inositol 1,4,5-trisphosphate-evoked calcium mobilisation in HEK-293 cells:: endogenous sphingosine-1-phosphate as a modulator of the calcium response
Enhancement of intracellular sphingosine-1-phosphate production by inositol 1,4,5-trisphosphate-evoked calcium mobilisation in HEK-293 cells:: endogenous sphingosine-1-phosphate as a modulator of the calcium response
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DOI：
10.1016/j.cellsig.2004.11.022
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Törnquist, K
中科院分区：
文献类型：
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作者：
Blom, T;Slotte, JP;Törnquist, K
鞘氨醇-1-磷酸（SIP）调节许多细胞功能，如迁移，分化和生长。S1 P的作用被认为主要是由G蛋白偶联受体介导的，但也提出了作为钙释放第二信使的细胞内功能。在这里，我们表明，在HEK-293细胞中，外源性SIP动员螯合钙的机制主要依赖于磷脂酶C（PLC）/肌醇1，4，5-三磷酸（IP 3）途径，其次是在随后的细胞内S1 P的合成。用SIP外源性刺激HEK-293细胞增加肌醇磷酸和细胞内S1 P的产生。在用2-APB、咖啡因或U 73122处理的细胞中，钙反应被抑制，表明用于钙释放的PLC/IP 3途径响应于外源性S1 P而被激活。在用鞘氨醇激酶抑制剂DMS处理的细胞和表达催化失活的鞘氨醇激酶的细胞中，钙响应被部分抑制，这表明内源性产生的S1 P也参与其中。重要的是，2-APB和U 73122抑制S1 P诱导的细胞内S1 P的产生。因此，S1 P不太可能是HEK-293细胞中主要的钙释放第二信使，而是钙动员的次级调节剂。(c)2004年爱思唯尔公司All rights reserved.
Sphingosine-1-phosphate (SIP) regulates many cellular functions, such as migration, differentiation and growth. The effects of S1P are thought to be primarily mediated by G-protein coupled receptors, but an intracellular function as a calcium releasing second messenger has also been proposed. Here we show that in HEK-293 cells, exogenous SIP mobilises sequestered calcium by a mechanism primarily dependent on the phospbolipase C (PLC)/inositol 1,4,5-trisphosphate (IP3) pathway, and secondarily on the subsequent synthesis of intracellular S1P. Stimulating HEK-293 cells exogenously with SIP increased the production of both inositol phosphates and intracellular S1P. The calcium response was inhibited in cells treated with 2-APB, caffeine or U73122, showing that the PLC/IP3 pathway for calcium release is activated in response to exogenous S1P. The calcium response was partially inhibited in cells treated with the sphingosine kinase inhibitor DMS and in cells expressing a catalytically inactive sphingosine kinase, showing that endogenously produced S1P is also involved. Importantly, 2-APB and U73122 inhibited the S1P-evoked production of intracellular S1P. S1P is therefore not likely a major calcium releasing second messenger in HEK-293 cells, but rather a secondary regulator of calcium mobilisation. (c) 2004 Elsevier Inc. All rights reserved.