Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2
Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2
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DOI：
10.1007/s00418-007-0344-0
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发表时间：
2008-02-01
影响因子：
2.3
通讯作者：
Eckhardt, Matthias
中科院分区：
文献类型：
--
作者：
Becker, Ivonne;Wang-Eckhardt, Lihua;Eckhardt, Matthias
二氢神经酰胺的合成由（二氢）神经酰胺脱氢酶（CerS）家族催化，该家族首先在酵母中被鉴定为长寿保证基因。在哺乳动物中已经鉴定出该基因家族的六个成员（CerS 1 -6; Lass 1 -6）。我们通过北方印迹分析、实时荧光定量RT-PCR和原位杂交检测了CerS基因在小鼠出生后发育过程中的表达。原位杂交实验表明，CerS 1是整个大脑神经元中的主要CerS。这一观察结果与神经元中C18：0-神经酰胺的高水平和CerS 1的底物特异性一致。CerS 4和CerS 6的分布相似，但表达水平较低。然而，在白色物质中只有少量或检测不到的CerS 1、CerS 4和CerS 6。相反，CerS 5 mRNA在所有脑区域的灰质和白色物质内的大多数细胞中检测到，表明这种棕榈酰辅酶A特异性CerS的普遍表达。CerS 2的表达在活跃的髓鞘形成期间短暂增加。此外，CerS 2的表达特异性地定位于脑的白色物质束。此外，CerS 2是坐骨神经雪旺细胞中的主要CerS。这些数据表明CerS 2对于用于合成髓鞘鞘脂的二氢神经酰胺的合成是重要的。
Synthesis of dihydroceramide is catalyzed by a family of (dihydro)ceramide synthases (CerS), first identified in yeast as longevity-assurance genes. Six members (CerS1-6; Lass1-6) of this gene family have been identified in mammals. We examined expression of CerS genes during postnatal development in mouse brain by means of Northern blot analysis, real-time RT-PCR, and in situ-hybridization. In situ-hybridization experiments showed that CerS1 was the predominant CerS in neurons throughout the brain. This observation is in line with the high levels of C18:0-ceramide in neurons and the substrate specificity of CerS1. A similar distribution, but lower expression levels, were found for CerS4 and CerS6. Only low or undetectable amounts of CerS1, CerS4 and CerS6 were, however, present in white matter. In contrast, CerS5 mRNA was detected in most cells within gray and white matter of all brain regions, suggesting ubiquitous expression of this palmitoyl-CoA specific CerS. Expression of CerS2 was transiently increased during the period of active myelination. Furthermore, expression of CerS2 was specifically localized to white matter tracts of the brain. Furthermore, CerS2 was the predominant CerS in Schwann cells of sciatic nerves. These data suggest that CerS2 is important for the synthesis of dihydroceramide used for synthesis of myelin sphingolipids.