Fyrst Henrik, Zhang Xinyi, Herr Deron R, Byun Hoe Sup, Bittman Robert, Phan Van H, Harris Greg L, Saba Julie D
Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
J Lipid Res. 2008 Mar;49(3):597-606. doi: 10.1194/jlr.M700414-JLR200. Epub 2007 Dec 21.
Sphingolipids comprise a complex group of lipids concentrated in membrane rafts and whose metabolites function as signaling molecules. Sphingolipids are conserved in Drosophila, in which their tight regulation is required for proper development and tissue integrity. In this study, we identified a new family of Drosophila sphingolipids containing two double bonds in the long chain base (LCB). The lipids were found at low levels in wild-type flies and accumulated markedly in Drosophila Sply mutants, which do not express sphingosine-1-phosphate lyase and are defective in sphingolipid catabolism. To determine the identity of the unknown lipids, purified whole fly lipid extracts were separated on a C18-HPLC column and analyzed using electrospray mass spectrometry. The lipids contain a LCB of either 14 or 16 carbons with conjugated double bonds at C4,6. The Delta(4,6)-sphingadienes were found as free LCBs, as phosphorylated LCBs, and as the sphingoid base in ceramides. The temporal and spatial accumulation of Delta(4,6)-sphingadienes in Sply mutants suggests that these lipids may contribute to the muscle degeneration observed in these flies.
鞘脂类是一类复杂的脂质，集中存在于膜筏中，其代谢产物作为信号分子发挥作用。鞘脂类在果蝇中是保守的，其严格调控对于果蝇的正常发育和组织完整性是必需的。在本研究中，我们鉴定出了一个新的果蝇鞘脂类家族，其长链碱基（LCB）含有两个双键。这些脂质在野生型果蝇中含量较低，而在果蝇Sply突变体中显著积累，Sply突变体不表达鞘氨醇-1-磷酸裂解酶，在鞘脂类分解代谢方面存在缺陷。为了确定这些未知脂质的身份，将纯化的全果蝇脂质提取物在C18-HPLC柱上进行分离，并用电喷雾质谱进行分析。这些脂质含有14或16个碳的LCB，在C4、6位带有共轭双键。Δ(4,6)-鞘氨二烯以游离LCB、磷酸化LCB以及神经酰胺中的鞘氨醇碱基形式存在。Δ(4,6)-鞘氨二烯在Sply突变体中的时空积累表明，这些脂质可能与这些果蝇中观察到的肌肉退化有关。
