Futerman A H
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Acta Biochim Pol. 1998;45(2):469-78.
Studies on the roles of sphingolipids (SLs) and glycosphingolipids (GSLs) at distinct stages of neuronal development have been performed using primary cultures of hippocampal neurons, which are unique among neuronal cultures inasmuch as they develop by a well-characterized and stereotypic sequence of events that gives rise to fully differentiated axons and dendrites. Our data demonstrate that SLs and GSLs play at least three distinct roles in regulating neuronal development, namely: (i) ceramide enhances the formation of minor neuronal processes from lamellipodia and the subsequent stage of axonogenesis; (ii) glucosylceramide synthesis, but not the synthesis of higher-order GSLs, is required for normal axon growth and for accelerated axonal growth upon stimulation by growth factors; and (iii) at both of these stages, ceramide at high concentrations can induce apoptotic cell death. Together, these observations are consistent with the possibility that minor process formation and apoptosis are regulated by ceramide-dependent signaling pathways, whereas axonal growth requires glucosylceramide synthesis, perhaps to support an intracellular transport pathway.
利用海马神经元原代培养物，对鞘脂（SLs）和糖鞘脂（GSLs）在神经元发育不同阶段的作用进行了研究。海马神经元原代培养物在神经元培养中独具特色，因为它们按照一系列特征明确且刻板的事件进行发育，最终形成完全分化的轴突和树突。我们的数据表明，鞘脂和糖鞘脂在调节神经元发育过程中至少发挥三种不同作用，即：（i）神经酰胺可增强片状伪足形成微小神经元突起以及随后轴突发生阶段的进程；（ii）正常轴突生长以及在生长因子刺激下加速轴突生长需要葡萄糖神经酰胺的合成，而非高阶糖鞘脂的合成；（iii）在这两个阶段，高浓度神经酰胺均可诱导凋亡性细胞死亡。综上所述，这些观察结果支持这样一种可能性，即微小突起形成和凋亡受神经酰胺依赖性信号通路调控，而轴突生长需要葡萄糖神经酰胺的合成，这可能是为了支持细胞内运输途径。
