Institute of General Pharmacology and Toxicology, Pharmazentrum Frankfurt, Goethe University, Frankfurt am Main, 60596, Frankfurt, Germany.
Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen, Goethe University Hospital, 60528, Frankfurt Am Main, Germany.
Pflugers Arch. 2024 Dec;476(12):1833-1843. doi: 10.1007/s00424-024-03018-8. Epub 2024 Sep 19.
Sphingosine-1-phosphate (S1P) is a bioactive lipid signaling molecule with pleiotropic implications by both auto- and paracrine signaling. Signaling occurs by engaging five G protein-coupled receptors (S1P) or intracellular pathways. While the extensively studied S1P with a chain length of 18 carbon atoms (d18:1 S1P) affects lymphocyte trafficking, immune cell survival and inflammatory responses, the biological implication of atypical S1Ps such as d16:1 or d20:1 remains elusive. As S1P lipids have far-reaching implications in health and disease states in mammalian organisms, the previous contrasting results may be attributed to differences in S1P's alkyl chain length. Current research is beginning to appreciate these less abundant atypical S1P moieties. This review provides an up-to-date foundation of recent findings on the biological implications of atypical S1P chain lengths and offers a perspective on future research endeavors on S1P alkyl chain length-influenced signaling and its implications for drug discovery.
鞘氨醇-1-磷酸(S1P)是一种具有多种生物学意义的生物活性脂质信号分子,通过自分泌和旁分泌信号传导。信号传导通过与五个 G 蛋白偶联受体(S1P)或细胞内途径结合来实现。虽然广泛研究的具有 18 个碳原子链长的 S1P(d18:1 S1P)影响淋巴细胞的迁移、免疫细胞的存活和炎症反应,但 d16:1 或 d20:1 等非典型 S1P 的生物学意义仍不清楚。由于 S1P 脂质在哺乳动物的健康和疾病状态中有广泛的影响,以前的对比结果可能归因于 S1P 烷基链长的差异。目前的研究开始认识到这些较少的非典型 S1P 部分。本综述提供了关于非典型 S1P 链长的生物学意义的最新研究结果的基础,并对 S1P 烷基链长影响的信号传导及其对药物发现的意义的未来研究工作提供了一个视角。