Ethanol triggers sphingosine 1-phosphate elevation along with neuroapoptosis in the developing mouse brain.
Ethanol triggers sphingosine 1-phosphate elevation along with neuroapoptosis in the developing mouse brain.
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DOI：
10.1111/j.1471-4159.2012.07723.x
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发表时间：
2012-06
影响因子：
4.7
通讯作者：
Saito M
中科院分区：
文献类型：
--
作者：
Chakraborty G;Saito M;Shah R;Mao RF;Vadasz C;Saito M
Our previous studies have indicated that de novo ceramide synthesis plays a critical role in ethanol-induced apoptotic neurodegeneration in the 7-day-old mouse brain. Here, we examined whether the formation of sphingosine 1-phosphate (S1P), a ceramide metabolite, is associated with this apoptotic pathway. Analyses of basal levels of S1P-related compounds indicated that S1P, sphingosine, sphingosine kinase 2, and S1P receptor 1 increased significantly during postnatal brain development. In the 7-day-old mouse brain, sphingosine kinase 2 was localized mainly in neurons. Subcellular fractionation studies of the brain homogenates showed that sphingosine kinase 2 was enriched in the plasma membrane and the synaptic membrane/synaptic vesicle fractions, but not in the nuclear and mitochondrial/lysosomal fractions. Ethanol exposure in 7-day-old mice induced sphingosine kinase 2 activation and increased the brain level of S1P transiently 2-4h after exposure, followed by caspase-3 activation that peaked around 8h after exposure. Treatment with dimethylsphingosine, an inhibitor of sphingosine kinases, attenuated the ethanol-induced caspase-3 activation and the subsequent neurodegeneration. These results indicate that ethanol activates sphingosine kinase 2, leading to a transient increase in S1P, which may be involved in neuroapoptotic action of ethanol in the developing brain.
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DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S
影响因子：
4.8
作者：
Araki, Y;Tomita, S;Suzuki, T
通讯作者：
Suzuki, T
烟酰胺可预防发育中的小鼠大脑中乙醇诱导的凋亡神经变性。
影响因子：
15.8
作者：
Ieraci, Alessandro;Herrera, Daniel G.
通讯作者：
Herrera, Daniel G.
DOI：
10.1016/j.jchromb.2009.02.048
发表时间：
2009-04-01
影响因子：
3
作者：
He, Xingxuan;Huang, Chien-Ling;Schuchman, Edward H.
通讯作者：
Schuchman, Edward H.
影响因子：
4.8
作者：
Ding, Guo;Sonoda, Hirofumi;Nakamura, Shun-ichi
通讯作者：
Nakamura, Shun-ichi