Phosphorylated cis-4-Methylsphingosine Mimics the Mitogenic Effect of Sphingosine-1-phosphate in Swiss 3T3 Fibroblasts*
Phosphorylated cis-4-Methylsphingosine Mimics the Mitogenic Effect of Sphingosine-1-phosphate in Swiss 3T3 Fibroblasts*
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磷酸化顺 4-甲基鞘氨醇模拟 1-磷酸鞘氨醇在 Swiss 3T3 成纤维细胞中的促有丝分裂作用*
DOI：
10.1074/jbc.273.36.23585
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
B. Schnieders
中科院分区：
文献类型：
--
作者：
G. van Echten;Andreas Schick;T. Heinemann;B. Schnieders
鞘氨醇的磷酸化衍生物，鞘氨醇-1-磷酸，是神经酰胺最终降解的短命代谢物，并被证明作为细胞内信号分子，刺激静止的Swiss 3T3成纤维细胞的细胞增殖，并诱导细胞内储存的钙的释放(Zhang， H., Desai， N. N., Olivera, a ., Seki， T., Brooker， G., and Spiegel， S. (1991) J. cell。生物学114,155-167)。在本研究中，用合成的鞘氨醇类似物-4-甲基鞘氨醇处理Swiss 3T3成纤维细胞24小时后，静止的Swiss 3T3成纤维细胞的增殖能力比等量鞘氨醇-1-磷酸强3倍。顺-4-甲基鞘氨醇的磷酸化衍生物在细胞内大量积累。与鞘氨醇激酶抑制剂orl-threo-sphinganine同时处理，磷酸化的顺式-4-甲基鞘氨醇的数量和该化合物诱导的细胞增殖均减少了约50%，表明磷酸化衍生物介导了增殖刺激。顺式-4-甲基鞘氨醇的有丝分裂作用与瑞士3T3成纤维细胞内钙的动员有关，这与鞘氨醇-1-磷酸诱导的相似。结果表明，磷酸化的顺-4-甲基鞘氨醇衍生物模拟了先前报道的鞘氨醇-1-磷酸在瑞士3T3细胞中的有丝分裂作用，并且更强的作用很可能与该化合物的异常积累相对应。
The phosphorylated derivative of sphingosine, sphingosine-1-phosphate, is a short-living metabolite of ultimate ceramide degradation and was shown to act as an intracellular signaling molecule, stimulating cell proliferation in quiescent Swiss 3T3 fibroblasts and inducing the release of calcium from intracellular stores (Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G., and Spiegel, S. (1991) J. Cell. Biol. 114, 155–167). In the present study, 24-h treatment of Swiss 3T3 fibroblasts with the synthetic sphingosine analoguecis-4-methylsphingosine resulted in proliferation of quiescent Swiss 3T3 fibroblasts that was 3-fold stronger than that of equimolar sphingosine-1-phosphate. The phosphorylated derivative ofcis-4-methylsphingosine accumulated drastically in the cells. Simultaneous treatment with the sphingosine kinase inhibitorl-threo-sphinganine reduced both the amount of phosphorylated cis-4-methylsphingosine and cell proliferation induced by this compound by about 50%, indicating that the phosphorylated derivative mediated the proliferative stimulus. The mitogenic effect of cis-4-methylsphingosine was associated with a mobilization of intracellular calcium in Swiss 3T3 fibroblasts that was similar to that induced by sphingosine-1-phosphate. The results demonstrate that the phosphorylated derivative ofcis-4-methylsphingosine mimics the previously reported mitogenic action of sphingosine-1-phosphate in Swiss 3T3 cells, and the stronger effect most likely corresponds to the unusual accumulation of this compound.
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影响因子：
56.9
作者：
Lee, MJ;Van Brocklyn, JR;Hla, T
通讯作者：
Hla, T
Sphingosine-1-磷酸是鞘氨醇的代谢产物，通过磷脂酶 D 激活增加磷脂酸水平。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Desai,NN;Zhang,H;Olivera,A;Mattie,ME;Spiegel,S
通讯作者：
Spiegel,S
体外和血小板中鞘氨醇激酶的抑制。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Buehrer,BM;Bell,RM
通讯作者：
Bell,RM
DOI：
10.1016/s0021-9258(19)40197-x
发表时间：
1990-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hong Zhang;N. E. Buckley;Karen Gibson;Sarah Spiegel
通讯作者：
Hong Zhang;N. E. Buckley;Karen Gibson;Sarah Spiegel
影响因子：
2.9
作者：
Y. Yatomi;F. Ruan;J. Ohta;R. Welch;S. Hakomori;Y. Igarashi
通讯作者：
Y. Yatomi;F. Ruan;J. Ohta;R. Welch;S. Hakomori;Y. Igarashi