Uemura K, Hara A, Taketomi T
Department of Lipid Biochemistry, Shinshu University School of Medicine, Nagano.
J Biochem. 1993 Oct;114(4):610-4. doi: 10.1093/oxfordjournals.jbchem.a124225.
Mouse neuroblastoma NS-20Y cells were induced to grow neurites by removal of serum from the medium. The percentage of cells with neurites reached about 50-60% after 24 h, whereas in medium containing 10% serum only a few cells (1-3%) were bearing neurites. Sphingosine inhibited the neuritogenesis in serum-free medium in a dose-dependent manner; a maximal effect was observed at 1-2 microM. Sphingosine also caused retraction of neurites which had been induced to extend in serum-free medium. N,N-Dimethylsphingosine was 10 times more potent in preventing neurite outgrowth, and N-acetylsphingosine was 10 times less effective compared to sphingosine. However, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) did not inhibit the extension of neurites. Neurite outgrowth in serum-free medium and its inhibition by sphingosine were still observed in the cells made protein kinase C-deficient by prolonged treatment with phorbol ester. These results suggest that the effect of sphingosine is not mediated by inhibition of protein kinase C.
通过去除培养基中的血清，诱导小鼠神经母细胞瘤NS - 20Y细胞长出神经突。24小时后，有神经突的细胞百分比达到约50 - 60%，而在含有10%血清的培养基中，只有少数细胞（1 - 3%）有神经突。鞘氨醇以剂量依赖的方式抑制无血清培养基中的神经突生成；在1 - 2微摩尔时观察到最大效应。鞘氨醇还导致在无血清培养基中已诱导延伸的神经突回缩。N，N - 二甲基鞘氨醇在阻止神经突生长方面的效力比鞘氨醇强10倍，而N - 乙酰鞘氨醇与鞘氨醇相比效力低10倍。然而，1 -（5 - 异喹啉磺酰基）- 2 - 甲基哌嗪（H - 7）并不抑制神经突的延伸。在用佛波酯长期处理使蛋白激酶C缺陷的细胞中，仍可观察到无血清培养基中的神经突生长及其被鞘氨醇抑制的现象。这些结果表明，鞘氨醇的作用不是通过抑制蛋白激酶C介导的。
