Conversion of cellular sialic acid expression from N-acetyl- to N-glycolylneuraminic acid using a synthetic precursor, N-glycolylmannosamine pentaacetate: inhibition of myelin-associated glycoprotein binding to neural cells
Conversion of cellular sialic acid expression from N-acetyl- to N-glycolylneuraminic acid using a synthetic precursor, N-glycolylmannosamine pentaacetate: inhibition of myelin-associated glycoprotein binding to neural cells
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DOI：
10.1093/glycob/10.1.11
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发表时间：
2000-01-01
期刊：
影响因子：
4.3
通讯作者：
Schnaar, RL
中科院分区：
文献类型：
--
作者：
Collins, BE;Fralich, TJ;Schnaar, RL
唾液酸是哺乳动物糖缀合物的主要末端，并且是细胞-细胞识别凝集素的关键结合决定簇。唾液酸依赖性凝集素、髓鞘相关糖蛋白（MAG）与神经细胞的结合涉及损伤后神经再生的抑制。因此，阻断MAG与神经细胞唾液酸糖缀合物的结合可能增强神经再生。以前，我们报道了某些携带N-乙酰神经氨酸（NeuAc）但不携带N-羟乙酰神经氨酸（NeuGc）的唾液酸糖缀合物支持MAG结合（柯林斯et at，1997 a）。我们现在报道了使用新的合成代谢前体N-羟乙酰甘露糖胺五乙酸酯（ManNGcPA）将活神经细胞上的唾液酸从仅NeuAc高效转化为主要的NeuGc。当NG 108 -15神经母细胞瘤-神经胶质瘤杂交细胞（通常仅表达NeuAc（并与MAG结合））在1 mM ManNGcPA存在下培养时，它们在24 h内将80-90%的唾液酸前体库表达为NeuGc，在5天内，80%的神经节苷脂相关唾液酸和70%的糖蛋白相关唾液酸转化为NeuGc。与该结果一致，用ManNGcPA处理NG 108 -15细胞导致MAG结合几乎完全消除。这些结果表明，ManNGcPA治疗有效地改变了活细胞上的唾液酸结构，在识别生理上重要的凝集素的相应变化。
Sialic acids are prominent termini of mammalian glycoconjugates and are key binding determinants for cell-cell recognition lectins, Binding of the sialic acid-dependent lectin, myelin-associated glycoprotein (MAG), to nerve cells is implicated in the inhibition of nerve regeneration after injury. Therefore, blocking MAG binding to nerve cell sialoglycoconjugates might enhance nerve regeneration. Previously, we reported that certain sialoglycoconjugates bearing N-acetylneuraminic acid (NeuAc) but not N-glycolylneuraminic acid (NeuGc) support MAG binding (Collins et at, 1997a), We now report highly efficient conversion of sialic acids on living neural cells from exclusively NeuAc to predominantly NeuGc using a novel synthetic metabolic precursor, N-glycolylmannosamine pentaacetate (ManNGcPA). When NG108-15 neuroblastoma-glioma hybrid cells, which normally express only NeuAc (and bind to MAG), mere cultured in the presence of 1 mM ManNGcPA, they expressed 80-90% of their sialic acid precursor pool as NeuGc within 24 h, Within 5 days, 80% of their ganglioside-associated sialic acids and 70% of their glycoprotein-associated sialic acids were converted to NeuGc. Consistent with this result, treatment of NG108-15 cells with ManNGcPA resulted in nearly complete abrogation of MAG binding. These results demonstrate that ManNGcPA treatment efficiently alters the sialic acid structures on living cells, with a commensurate change in recognition by a physiologically important lectin.