Anelli Viviana, Bassi Rosaria, Tettamanti Guido, Viani Paola, Riboni Laura
Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Segrate, Milan, Italy.
J Neurochem. 2005 Mar;92(5):1204-15. doi: 10.1111/j.1471-4159.2004.02955.x.
Sphingosine-1-phosphate (S1P) is a potent biomediator that can act as either an intracellular or an intercellular messenger. In the nervous system it exerts a wide range of actions, and specific membrane receptors for it have been identified in various regions. However, the physiological origin of extracellular S1P in the nervous system is largely unknown. We investigated cerebellar granule cells at different stages of differentiation and astrocytes in primary cultures as possible origins of extracellular S1P. Although these cells show marked differences in S1P metabolism, we found that they can all release S1P and express mRNAs for S1P specific receptors. Extracellular S1P derives from the export of newly synthesized intracellular S1P, and not from the action of a released sphingosine kinase. S1P release is rapid, efficient, and can be regulated by exogenous stimuli. Phorbol ester treatment resulted in an increase in sphingosine kinase 1 activity in the membranes, accompanied by a significant increase in extracellular S1P. S1P release in cells from the cerebellum emerges as a regulated mechanism, possibly related to a specific pool of newly synthesized S1P. To our knowledge, this is the first evidence of the extracellular release of S1P by primary cells from the CNS, which supports a role of S1P as autocrine/paracrine physiological messenger in the cerebellum.
鞘氨醇-1-磷酸（S1P）是一种强效生物介质，可作为细胞内或细胞间信使发挥作用。在神经系统中，它发挥着广泛的作用，并且已在各个区域鉴定出其特异性膜受体。然而，神经系统中细胞外S1P的生理来源在很大程度上尚不清楚。我们研究了原代培养中处于不同分化阶段的小脑颗粒细胞和星形胶质细胞，将其作为细胞外S1P的可能来源。尽管这些细胞在S1P代谢方面表现出明显差异，但我们发现它们都能释放S1P并表达S1P特异性受体的mRNA。细胞外S1P源自新合成的细胞内S1P的输出，而非来自释放的鞘氨醇激酶的作用。S1P的释放迅速、高效，且可受外源刺激调节。佛波酯处理导致膜中鞘氨醇激酶1活性增加，同时细胞外S1P显著增加。小脑细胞中S1P的释放是一种受调节的机制，可能与新合成的S1P的特定池有关。据我们所知，这是中枢神经系统原代细胞释放细胞外S1P的首个证据，支持了S1P在小脑中作为自分泌/旁分泌生理信使的作用。
