Disruption of GM2/GD2 synthase gene resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21.
Disruption of GM2/GD2 synthase gene resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21.
复制标题
GM2/GD2合酶基因的破坏导致9-O-乙酰基GD3的明显表达，而TIS21无关。
DOI：
10.1111/j.1471-4159.2008.05232.x
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发表时间：
2008-05
影响因子：
4.7
通讯作者：
Furukawa, Koichi
中科院分区：
文献类型：
--
作者：
Furukawa, Keiko;Aixinjueluo, Wei;Kasama, Takeshi;Ohkawa, Yuki;Yoshihara, Michiko;Ohmi, Yusuke;Tajima, Orie;Suzumura, Akio;Kittaka, Daiji;Furukawa, Koichi
GM2/GD2合酶基因敲除小鼠缺乏所有复杂的神经节苷脂，而这些神经节苷脂在脊椎动物的神经系统中大量表达。反过来，它们增加了前体结构 GM3 和 GD3，可能取代了耗尽的复合神经节苷脂的作用。在这项研究中，我们发现9-O-乙酰基GD3也作为主要的鞘糖脂之一高表达，在突变小鼠的神经组织中积累。通过神经氨酸酶处理、薄层色谱-免疫染色、碱处理二维薄层色谱和质谱法证实了新成分的身份。据报道，所有候选因子可能是 9-O- 乙酰化的诱导剂，例如比特胺 D 结合蛋白、乙酰 CoA 转运蛋白或 O-乙酰神经节苷脂合酶，均未上调。据报道，Tis21 是 9-O-乙酰化诱导剂，在无效突变体中部分下调，表明 Tis21 不参与 9-O-乙酰基-GD3 的诱导，大量积累的 GD3 可能是 9-O-乙酰基 GD3 急剧增加的主要因素。对正常小鼠星形胶质细胞中外源添加的 GD3 乙酰化的能力进行了检查，结果表明野生型大脑可能能够合成非常低水平的 9-O-乙酰基 GD3。除了 GM3 和 GD3 之外，9-O-乙酰基 GD3 的增加可能在突变小鼠中缺失的复合神经节苷脂的补偿中发挥重要作用。 J.神经化学。 (2008) 105, 1057–1066。
GM2/GD2 synthase gene knockout mice lack all complex gangliosides, which are abundantly expressed in the nervous systems of vertebrates. In turn, they have increased precursor structures GM3 and GD3, probably replacing the roles of the depleted complex gangliosides. In this study, we found that 9-O-acetyl GD3 is also highly expressed as one of the major glycosphingolipids accumulating in the nervous tissues of the mutant mice. The identity of the novel component was confirmed by neuraminidase treatment, thin layer chromatography-immunostaining, two-dimensional thin layer chromatography with base treatment, and mass spectrometry. All candidate factors reported to be possible inducer of 9-O- acetylation, such as bitamine D binding protein, acetyl CoA transporter, or O-acetyl ganglioside synthase were not up-regulated. Tis21 which had been reported to be a 9-O-acetylation inducer was partially down-regulated in the null mutants, suggesting that Tis21 is not involved in the induction of 9-O-acetyl-GD3 and that accumulated high amount of GD3 might be the main factor for the dramatic increase of 9-O-acetyl GD3. The ability to acetylate exogenously added GD3 in the normal mouse astrocytes was examined, showing that the wild-type brain might be able to synthesize very low levels of 9-O-acetyl GD3. Increased 9-O-acetyl GD3, in addition to GM3 and GD3, may play an important role in the compensation for deleted complex gangliosides in the mutant mice. J. Neurochem. (2008) 105, 1057–1066.
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影响因子：
6.5
作者：
Fahr, C;Schauer, R
通讯作者：
Schauer, R
影响因子：
2.9
作者：
FURUKAWA, K;CLAUSEN, H;LLOYD, KO
通讯作者：
LLOYD, KO
DOI：
10.1073/pnas.0503658102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Hamamura, K;Furukawa, K;Furukawa, K
通讯作者：
Furukawa, K
DOI：
10.1590/s0100-879x2001000500016
发表时间：
2001-05-01
影响因子：
2.3
作者：
Miyakoshi, LM;Mendez-Otero, R;Hedin-Pereira, C
通讯作者：
Hedin-Pereira, C
DOI：
10.1016/0006-291x(88)90457-3
发表时间：
1988-01-29
影响因子：
3.1
作者：
NAKAISHI, H;SANAI, Y;NAGAI, Y
通讯作者：
NAGAI, Y