Sphingolipids which regulate the cell functions in neuronal cells.

(1)血清剥夺诱导的小鼠神经母细胞瘤NS-20Y细胞神经突生长受到shingosin （1- 2mum）和葡萄糖神经酰胺合成酶抑制剂（1-phenyl-2-decanoylamino-3-morpholino-3-propanol）的抑制。通过检测几种抑制剂对神经突发生的影响，探讨了蛋白激酶和钙调蛋白在调节神经突生长中的作用。W-7 (10muM)，卡咪唑（0.3muM）和三氟拉嗪（0.1muM），这些药物被报道可以抑制钙调素依赖事件，减少神经突起的生长。另一方面，H-7和H-89无效，染料木素不影响携带神经突的细胞数量。被这些抑制剂阻断的蛋白激酶的激活似乎对神经突的延伸和维持不是必需的。KN-62和KN-93 （Ca^<2+>/钙调素依赖性蛋白激酶II的抑制剂）不抑制神经突的生长。这些结果表明，在无血清培养基中，除Ca^<2+>/钙调素依赖性蛋白激酶II的活性增加外，一个钙调素依赖性过程参与了小鼠神经母细胞瘤NS-20Y细胞的神经发生。鞘氨醇对神经突生长的抑制作用很可能是由于钙调蛋白的抑制作用。(2)采用流式细胞术研究了一系列鞘氨醇衍生物和糖基神经酰胺合成酶抑制剂PDMP（1-苯基-2-癸酰氨基-3- morpholinos -1-丙醇）对小鼠神经母细胞瘤NS-20Y细胞周期进程的影响。在PDMP的作用下（50muM,24h）， S期细胞比例减少，而G0/G1期细胞比例显著增加。鞘氨醇、鞘氨醇、鞘氨醇-1-磷酸、短链神经酰胺（n -乙酰或n -己醇-鞘氨醇）或鞘氨醇-磷胆碱对细胞周期没有影响。未观察到细胞凋亡特征的DNA峰。这些结果表明，PDMP对NS-20Y细胞增殖的抑制是由其对细胞周期进程的影响引起的，更可能是由于鞘糖脂水平的降低而不是神经酰胺或鞘脂水平的增加。少

(1) Neurite outgrowth in murine neuroblastoma NS-20Y cells induced by serum deprivation was inhibited by shingosine (1-2muM) as well as by an inhibitor of glucosylceramide synthase (1-phenyl-2-decanoylamino-3-morpholino-3-propanol). The roles of protein kinases and calmodulin in regulating neurite outgrowth were investigated by testing the effect of several inhibitors on the neuritogenesis. W-7 (10muM), calmidazolium (0.3muM) and trifluoperazine (0.1muM), drugs reported to inhibit calmodulin-dependent events, reduced neurite outgrowth. On the other hand, H-7 and H-89 were ineffective, and genistein did not affect the number of cells bearing neurites. Activation of protein kinases, which are blocked by these inhibitors, does not appear to be essential to the extension and maintenance of neurites. KN-62 and KN-93 (inhibitors of Ca^<2+>/calmodulin-dependent protein kinase II) did not inhibit neurite outgrowth. These results suggest that a calmodulin-dependent process, other than the activ … More ation of Ca^<2+>/calmodulin-dependent protein kinase II,is involved in neuritogenesis of murine neuroblastoma NS-20Y cells in serum-free medium. The inhibitory effect of sphingosine on neurite outgrowth is most likely due to calmodulin inhibition.(2) The effects of a series of sphingosine derivatives and an inhibitor of glucosylceramide synthase, PDMP (1-phenyl-2-decanoylamino-3-morpholino-1-propanol), on the cell cycle progression of murine neuroblastoma NS-20Y cells were investigated by flow cytometry. In the presence of PDMP (50muM,24h) the proportion of cells in the S phase was reduced, whereas that in the G0/G1 phase significantly increased. Incubation of cells with sphingosine, sphinganine, sphingosine-1-phosphate, short-chain ceramides (N-acethyl-or N-hexanoyl-sphingosine) or sphingosyl-phosphocholine did not affect the cell cycle. The DNA peaks characteristic of apoptosis were not observed. These results suggest that the inhibition of the proliferation of NS-20Y cells by PDMP is caused by its effect on cell cycle progression and is more likely due to the reduced levels of glycosphingolipids rather than the increased levels of ceramide or sphingosine. Less