Changes in N-linked sugar chain patterns induced by moderate-to-high expression of the galactosyltransferase I gene in a brain-derived cell line, CG4
Changes in N-linked sugar chain patterns induced by moderate-to-high expression of the galactosyltransferase I gene in a brain-derived cell line, CG4
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DOI：
10.1002/jnr.20416
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发表时间：
2005-04-01
影响因子：
4.2
通讯作者：
Ikenaka, K
中科院分区：
文献类型：
--
作者：
Menon, KN;Ikeda, T;Ikenaka, K
在β1-4三甘露醇核心(BA2)的甘露糖上附着有两个触角的寡糖和N-乙酰氨基葡萄糖(GlcNAc)的二等分残基(Ba2)在大脑中丰富，被认为是脑型糖链。我们研究了半乳糖基转移酶I(GalTase 1)与脑源性细胞系CG4中Ba2形成之间相互作用的意义。在不同的神经胶质和神经元来源的细胞系中，GalTase的表达增加伴随着Ba2的降低或检测不到，这取决于GalTase的表达水平。在表达高水平Ba2和低GalTase活性的CG4细胞中，GalTase I的强烈表达显著降低了Ba2的水平。此外，异常糖链A1(6)G1Fo增加了6倍，A2G2Fo(6)F适度增加。A1(6)G1Fo水平的升高表明N连接的糖链生物合成途径从正常转向或取消。A1(6)G1Fo的积累和A2G2Fo(6)F水平的增加伴随着高甘露糖型糖链M5A、M6B、M8A和M9A水平的下降。GalTase I表达增加还导致CG4细胞生长受阻和形态异常，死亡率增加。因此，即使是适度的GalTase I的过度表达也会扰乱N-连接糖链的正常生物合成途径，而高水平的过度表达对CG4细胞是致命的。(C)2005年Wiley-Liss，Inc.
Oligosaccharides with biantennae and bisecting N-acetyl glucosamine (GlcNAc) residues attached to the mannose in the beta 1-4 trimannosyl core (BA2) are enriched in the brain and considered brain-type sugar chains. We investigated the significance of the interplay between galactosyltransferase I (GalTase 1) and BA2 formation in a brain-derived cell line, CG4. Increased GalTase expression in different glial- and neuronal-derived cell lines was accompanied by decreased or undetectable levels of BA2, depending on the level of GalTase expression. Forceful expression of GalTase I in CG4 cells expressing high levels of BA2 and low GalTase activity significantly reduced BA2 levels. In addition, a sixfold increase in an abnormal sugar chain A1(6)G1Fo and a moderate increase in A2G2Fo(6)F were evident. The increased levels of A1(6)G1Fo indicate a diversion or abrogation of the N-linked sugar chain biosynthetic pathway from normal. The accumulation of A1(6)G1Fo and increased A2G2Fo(6)F levels were accompanied by decreased levels of the high mannose-type sugar chains, M5A, M6B, M8A, and M9A. Increased GalTase I expression also led to stunted growth and abnormal morphology of CG4 cells, with increased mortality. Even moderate overexpression of GalTase I thus disrupts the normal biosynthetic pathway of N-linked sugar chains, and high overexpression is fatal to CG4 cells. (c) 2005 Wiley-Liss, Inc.