Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.
Adv Exp Med Biol. 2010;688:118-30. doi: 10.1007/978-1-4419-6741-1_8.
An important metabolite of ceramide is ceramide-1-phosphate (C1P). This lipid second messenger was first demonstrated to be mitogenic for fibroblasts and macrophages and later shown to have antiapoptotic properties. C1P is also an important mediator of the inflammatory response, by stimulating the release of arachidonic acid through activation of group IVA cytosolic phospholipase A2, the initial rate-limiting step of eicosanoid biosynthesis. C1P is formed from ceramide by the action of a specific ceramide kinase (CerK), which is distinct from the sphingosine kinases that synthesize sphingosine-1-phosphate. CerK is specific for natural ceramides with the erythro configuration in the base component and esterified to long-chain fatty acids. CerK can be activated by different agonists, including interleukin 1-beta, macrophage colony stimulating factor, or calcium ions. Most of the effects of C1P so far described seem to take place in intracellular compartments; however, the recent observation that C1P stimulates cell migration implicates a specific plasma membrane receptor that is coupled to a G(i) protein. Therefore, C1P has a dual regulatory capacity acting as an intracellular second messenger to regulate cell survival, or as extracellular receptor ligand to stimulate chemotaxis.
神经酰胺的一种重要代谢产物是神经酰胺-1-磷酸（C1P）。这种脂质第二信使最初被证明对成纤维细胞和巨噬细胞具有有丝分裂原作用，后来又被证明具有抗凋亡作用。C1P 也是炎症反应的重要介质，通过激活 IVA 胞质磷脂酶 A2，刺激花生四烯酸的释放，从而刺激花生四烯酸的释放，从而刺激花生四烯酸的释放，从而刺激花生四烯酸的释放。花生四烯酸的释放。花生四烯酸的释放。C1P 是由特定的神经酰胺激酶（CerK）作用于神经酰胺形成的，CerK 与合成神经酰胺-1-磷酸的鞘氨醇激酶不同。CerK 对具有赤型构型的天然神经酰胺具有特异性，并且与长链脂肪酸酯化。CerK 可以被不同的激动剂激活，包括白细胞介素 1-β、巨噬细胞集落刺激因子或钙离子。迄今为止，C1P 描述的大多数作用似乎发生在细胞内隔室中；然而，最近的观察结果表明，C1P 刺激细胞迁移，暗示存在与 G(i) 蛋白偶联的特定质膜受体。因此，C1P 具有双重调节能力，作为细胞内第二信使调节细胞存活，或作为细胞外受体配体刺激趋化性。
