Sullards M C, Wang E, Peng Q, Merrill A H
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA.
Cell Mol Biol (Noisy-le-grand). 2003 Jul;49(5):789-97.
Sphingolipids participate in membrane structure and signaling in neuronal cells, and an emerging strategy for control of gliomas is to inhibit growth and/or induce apoptosis using ceramide and ceramide analogs. Nonetheless, some sphingolipids (ceramides and sphingosine) induce and others (sphingosine 1-phosphate) inhibit apoptosis; therefore, when testing putative anti-cancer agents, it is critical to obtain precise knowledge of the types and quantities of not only the test compounds, but also their effects on endogenous species. Combination of liquid chromatography and tandem mass spectrometry affords a "metabolomic" profile of all of the intermediates of ceramide biosynthesis (3-ketosphinganine, sphinganine and dihydroceramides) and the direct products of ceramide metabolism (sphingomyelins and monohexosylceramides as well as sphingosine and sphingosine 1-phosphate). This method has been applied to four human glioma cell lines (LN18, LN229, LN319 and T98G), and differences in the amounts and types of sphingolipids were found. For example, LN229 and LN319 have approximately twice the sphingosine 1-phosphate of LN18 and T98G; LN229 and LN319 have more monohexosylceramides than lactosylceramides, whereas the opposite is the case for LN18 and T98G; and the fatty acyl chain distributions of the sphingolipids differ among the cell lines. The ability to obtain this type of "metabolomic" profile allows studies of how anti-cancer agents (especially sphingolipids and sphingolipid analogs) affect the amounts of these bioactive species, and may lead to a better understanding of the abnormal phenotypes of gliomas.
鞘脂参与神经元细胞膜结构及信号传导，而控制胶质瘤的一种新策略是使用神经酰胺及其类似物抑制肿瘤生长和/或诱导细胞凋亡。然而，一些鞘脂（神经酰胺和鞘氨醇）可诱导细胞凋亡，而另一些（1-磷酸鞘氨醇）则抑制细胞凋亡；因此，在测试潜在抗癌药物时，不仅要精确了解测试化合物的种类和数量，还要了解其对内源性物质的影响。液相色谱与串联质谱联用可提供神经酰胺生物合成所有中间体（3-酮二氢鞘氨醇、二氢鞘氨醇和二氢神经酰胺）以及神经酰胺代谢直接产物（鞘磷脂、单己糖神经酰胺以及鞘氨醇和1-磷酸鞘氨醇）的“代谢组”图谱。该方法已应用于四种人类胶质瘤细胞系（LN18、LN229、LN319和T98G），并发现了鞘脂在数量和种类上的差异。例如，LN229和LN319的1-磷酸鞘氨醇含量约为LN18和T98G的两倍；LN229和LN319的单己糖神经酰胺比乳糖基神经酰胺多，而LN18和T98G则相反；并且不同细胞系中鞘脂的脂肪酰基链分布也有所不同。获得这种“代谢组”图谱的能力有助于研究抗癌药物（尤其是鞘脂及其类似物）如何影响这些生物活性物质的含量，并可能有助于更好地理解胶质瘤的异常表型。
