Hoch ungesättigte Sphingolipide: Biosynthese Expression und biologische Funktion während der Spermatogenese

高度不饱和鞘脂：精子发生过程中的生物合成表达和生物学功能

• 批准号: 27849200
• 负责人: Privatdozent Dr. Roger Sandhoff
• 金额: --
• 依托单位: Abteilung Zelluläre und Molekulare Pathologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/27849200?language=en
• 关键词: Hoch; unges; ttigte; Sphingolipide; Biosynthese

In contrast to cholesterol and phospholipids including sphingomyelin, glycosphingolipids (GSLs) are cell type and differentiation stage specifically expressed in mammalian cells and contain almost exclusively saturated fatty acid residues. Not only the sugar head groups of GSLs but also their membrane anchors, i.e. the ceramide moieties including the N-linked fatty acyl chain show a cell type specific pattern (Kolter and Sandhoff, 1999). In our previous work we discovered in mouse testis, structurally characterized and to some extent histologically localized, a novel class of GSLs (8 members in mice). They were defined as a novel class because these fucosylated GSLs (FGSLs) contain almost exclusively polyunsaturated (polyenoic, 4-6 double bonds) very long chain (C28-C32) fatty acyl (VLCFA) residues (Sandhoff et al., 2005). Mice lacking ganglio-series GSLs are also deficient in this novel type of testicular polyenoic FGSLs. Spermatogenesis of such mice is arrested at the stage of immature round spermatids with the consequence of male infertility (Takamiya et al., 1998). The aim of this project is to understand the biosynthesis, localization and biological function of this novel class of polyunsaturated sphingolipids. Besides expanding the basic knowledge in this field, the expected results of this project may help to gain deeper insight into the possible causes of male infertility. They may, in addition, open new fields for male contraception.

与胆固醇和磷脂（包括鞘磷脂）相反，鞘糖脂（GSL）是在哺乳动物细胞中特异性表达的细胞类型和分化阶段，并且几乎仅含有饱和脂肪酸残基。不仅GSL的糖头基团，而且它们的膜锚，即包括N-连接的脂肪酰基链的神经酰胺部分显示出细胞类型特异性模式（Kolter和Sandhoff，1999）。在我们以前的工作中，我们在小鼠睾丸中发现了一类新的GSL（小鼠中有8个成员），其结构特征和一定程度的组织学定位。它们被定义为新的类别，因为这些岩藻糖基化GSL（FGSL）几乎仅含有多不饱和（多烯，4-6个双键）极长链（C28-C32）脂肪酰基（VLCFA）残基（Sandhoff等人，2005年）。缺乏神经节系列GSL的小鼠也缺乏这种新型的睾丸多烯FGSL。这种小鼠的精子发生在未成熟的圆形精子细胞阶段被阻止，结果导致雄性不育（Takamiya等人，1998年）。该项目的目的是了解这种新型多不饱和鞘脂的生物合成，定位和生物学功能。除了扩展该领域的基础知识外，该项目的预期结果可能有助于更深入地了解男性不育的可能原因。此外，它们还可能为男性避孕开辟新的领域。