Elevation of ceramide within distal neurites inhibits neurite growth in cultured rat sympathetic neurons
Elevation of ceramide within distal neurites inhibits neurite growth in cultured rat sympathetic neurons
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DOI：
10.1074/jbc.272.5.3028
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发表时间：
1997-01-31
影响因子：
4.8
通讯作者：
Vance, JE
中科院分区：
文献类型：
--
作者：
deChaves, EIP;Bussiere, M;Vance, JE
鞘脂是神经元膜的丰富成分，参与细胞内信号传导。我们发现鞘糖脂生物合成中间体的两种类似物，伏马菌素B-1（抑制二氢神经酰胺合成）和dl -1-苯基-2-棕榈酰氨基-3- morpholinos -1-丙醇（PPMP）（抑制葡萄糖神经酰胺合成）减少大鼠交感神经元鞘糖脂合成。虽然伏马菌素和PPMP都抑制鞘糖脂合成，但这些抑制剂对轴突神经酰胺代谢的影响不同。三ppmp，而不是红ppmp或伏马菌素，诱导[H-3]棕榈酸标记神经酰胺的积累并损害轴突生长。此外，外源性添加的细胞渗透性c -6神经酰胺，而不是c -6-二氢神经酰胺，模仿PPMP的效果。我们的研究表明，脂质第二信使神经酰胺作为神经突生长的负调节因子作用于远端轴突，而不是细胞体。
Sphingolipids are abundant constituents of neuronal membranes and have been implicated in intracellular signaling. We show that two analogs of glycosphingolipid biosynthetic intermediates, fumonisin B-1 (which inhibits dihydroceramide synthesis) and DL-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) (which inhibits glucosylceramide synthesis) decrease glycosphingolipid synthesis in rat sympathetic neurons. Although both fumonisin and PPMP inhibit glycosphingolipid synthesis, these inhibitors have differential effects on ceramide metabolism in axons. threo-PPMP, but not erythro-PPMP or fumonisin, induces an accumulation of [H-3]palmitate-labeled ceramide and impairs axonal growth. Moreover, exogenously added, cell-permeable C-6-ceramide, but not C-6-dihydroceramide, mimicks the effect of PPMP. Our studies suggest that the lipid second messenger ceramide acts in distal axons, but not cell bodies, as a negative regulator of neurite growth.