The human blood fluke Schistosoma mansoni synthesizes a novel type of glycosphingolipid.
The human blood fluke Schistosoma mansoni synthesizes a novel type of glycosphingolipid.
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DOI：
10.1016/s0021-9258(18)45870-x
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发表时间：
1992-02
期刊：
影响因子：
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通讯作者：
C K Makaaru;R. Damian;D. F. Smith;R. Cummings
中科院分区：
文献类型：
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作者：
C K Makaaru;R. Damian;D. F. Smith;R. Cummings
先前的研究表明，曼氏血吸虫成虫（人类血吸虫病的病原体）合成的糖蛋白寡糖是不寻常的，因为它们含有末端β-GalNAc残基，缺乏唾液酸。这些观察结果和其他研究表明，在感染的动物中，鞘糖体糖蛋白和糖脂具有抗原性，这促使我们研究这些生物体合成的鞘糖脂的结构，并确定它们是否与脊椎动物宿主合成的鞘糖脂结构相关。在我们的研究中，成年人的鞘氨醇体代谢放射性标记的[3 H]半乳糖或[3 H]葡糖胺，和新合成的鞘糖脂的分离和表征。发现成体鞘脂体合成的主要鞘糖脂是半乳糖神经酰胺和葡萄糖神经酰胺。蠕虫不合成乳糖神经酰胺（Gal β 1- 4Glc-神经酰胺），这是脊椎动物细胞的一种常见成分;然而，发现了另一种可被神经酰胺聚糖酶裂解的含有二硫代氨基甲酸酯的鞘糖脂，其组成和甲基化分析以及外切糖苷酶处理的结果表明，这种神经酰胺二糖具有GalNAc β 1- 4Glc-神经酰胺的结构。我们还发现，成人的β-半乳糖体的提取物不能将半乳糖从UDP-半乳糖转移到葡萄糖神经酰胺，而作为对照的中国仓鼠卵巢细胞的提取物能够这样做，证实β-半乳糖体不能合成乳糖神经酰胺。低水平的较高分子量的鞘糖脂也被认为是由成年人的神经鞘脂体合成，虽然他们的水平太小，允许明确的表征，成分分析表明，他们也包含GalNAc。我们已初步命名为新的二糖结构GalNAc β 1，4Glc-“β-核心”，这可能代表了一种新型的鞘糖脂核心系列。
Previous studies have shown that the glycoprotein oligosaccharides synthesized by adult Schistosoma mansoni, the organism responsible for human schistosomiasis, are unusual in that they contain terminal beta-GalNAc residues and lack sialic acid. These observations and other studies indicating that schistosome glycoproteins and glycolipids are antigenic in infected animals led us to investigate the structures of the glycosphingolipids synthesized by these organisms and to determine whether they are structurally related to those synthesized by their vertebrate hosts. For our studies, adult schistosomes were metabolically radiolabeled with either [3H]galactose or [3H]glucosamine, and the newly synthesized glycosphingolipids were isolated and characterized. The major glycosphingolipids synthesized by adult schistosomes were found to be galactosylceramide and glucosylceramide. The adult worms synthesized no lactosylceramide (Gal beta 1-4Glc-ceramide), a common constituent of vertebrate cells; however, another disaccharide-containing glycosphingolipid cleavable by ceramide glycanase was found. The results of compositional and methylation analyses and exoglycosidase treatments demonstrated that this ceramide-disaccharide has the structure GalNAc beta 1-4Glc-ceramide. We also found that extracts of adult schistosomes are unable to transfer Gal from UDP-Gal to glucosylceramide, whereas extracts of Chinese hamster ovary cells, as a control, are able to do so, confirming that schistosomes are unable to synthesize lactosylceramide. Low levels of higher molecular weight glycosphingolipids were also found to be synthesized by adult schistosomes, and although their levels were too small to allow definitive characterization, compositional analyses indicated that they also contained GalNAc. We have tentatively designated the new disaccharide structure GalNAc beta 1, 4Glc- the “schistocore”, which may represent a new type of glycosphingolipid core series.