Inhibition of sphingolipid synthesis affects axonal outgrowth in cultured hippocampal neurons.
Inhibition of sphingolipid synthesis affects axonal outgrowth in cultured hippocampal neurons.
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发表时间：
1993-07
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通讯作者：
Rotem Harel;A. Futerman
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作者：
Rotem Harel;A. Futerman
神经元的生长受到细胞外和细胞决定因素的调节，并且被认为是通过在生长锥处添加新的膜材料来进行的。为了确定脂质合成是否是维持神经元生长所必需的，我们研究了神经酰胺合成抑制剂伏马菌素 B1 对培养的海马神经元发育的影响。 Fumonisin B1 在体内和体外均可抑制海马神经元的神经酰胺合成。伏马菌素 B1 处理后神经节苷脂合成和含量减少，免疫荧光在细胞表面检测不到神经节苷脂 GD1b。伏马菌素 B1 抑制鞘脂合成对轴突生长有显着影响。在培养第2-3天之间，平均轴突长度从170微米增加到240微米，但在伏马菌素处理的细胞中，没有观察到轴突长度增加。添加神经酰胺荧光衍生物和伏马菌素 B1 可逆转这种效应，证实伏马菌素 B1 通过抑制神经酰胺合酶发挥作用。此外，神经酰胺本身导致轴突长度显着增加。我们讨论了抑制鞘脂合成可能破坏轴突生长的三种可能机制，其中可能是持续的鞘脂合成对于为生长的轴突提供新的膜材料是必要的。
Neuronal growth is regulated by both extracellular and cellular determinants and is believed to proceed by the addition of new membrane material at the growth cone. To determine whether lipid synthesis is necessary to maintain neuronal growth, we have examined the effect of Fumonisin B1, an inhibitor of ceramide synthesis, on the development of cultured hippocampal neurons. Fumonisin B1 inhibits ceramide synthesis in hippocampal neurons both in vivo and in vitro. Ganglioside synthesis and content was reduced after Fumonisin B1 treatment, and ganglioside GD1b was not detectable at the cell surface by immunofluorescence. Inhibition of sphingolipid synthesis by Fumonisin B1 had a significant effect on axonal growth. Between days 2-3 in culture, mean axon length increased from 170 to 240 microns, but in Fumonisin-treated cells, no increase in axon length was observed. Addition of a fluorescent derivative of ceramide together with Fumonisin B1 reversed this effect, confirming that Fumonisin B1 acts via inhibition of ceramide synthase. Further, ceramide by itself caused a significant increase in axon length. We discuss three possible mechanisms by which inhibition of sphingolipid synthesis could disrupt axonal growth, among them the possibility that ongoing sphingolipid synthesis is necessary to provide new membrane material to the growing axon.