Action of monensin, a monovalent cationophore, on cultured human fibroblasts: evidence that it induces high cellular accumulation of glucosyl- and lactosylceramide (gluco- and lactocerebroside).
Action of monensin, a monovalent cationophore, on cultured human fibroblasts: evidence that it induces high cellular accumulation of glucosyl- and lactosylceramide (gluco- and lactocerebroside).
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莫能菌素（一种单价阳离子载体）对培养的人成纤维细胞的作用：有证据表明它会诱导葡萄糖基神经酰胺和乳糖神经酰胺（葡萄糖脑苷脂和乳糖脑苷脂）在细胞内大量积累。
DOI：
10.1021/bi00301a001
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
A. Rosenberg
中科院分区：
文献类型：
--
作者：
M. Saito;A. Rosenberg
我们已经将培养的人成纤维细胞暴露于微摩尔浓度的离子载体莫能菌素。一个显著的结果是葡萄糖神经酰胺(葡萄糖脑苷脂，GlcCer)和乳糖基神经酰胺(乳脑苷脂，LacCer)在这些细胞中迅速积累。当我们用放射性标记的半乳糖孵育这些细胞时，GlcCer和LacCer变得高度标记。这些结果表明，莫能菌素大大增加了这些最简单的糖鞘糖脂，这些糖脂是主要的质膜糖鞘糖脂的前体。同时，我们观察到，标记的半乳糖掺入一些糖基化程度较高的中性鞘糖脂和唾液酸鞘糖脂(神经节苷脂)中的比例降低，与GlcCer和LacCer不同，这些高度糖基化的化合物在存在或不存在莫能菌素的情况下细胞含量保持不变。我们发现，培养的高谢病成纤维细胞，具有遗传受损的溶酶体葡萄糖脑苷酶活性，在暴露于莫能菌素时，比正常细胞积累更多的GlcCer和LacCer。这一发现表明，莫能菌素影响生物合成，而不仅仅是破坏溶酶体的降解，而溶酶体的降解已经在高谢病细胞中删除了GlcCer。这些结果首次表明单价离子载体莫能菌素对质膜糖鞘糖脂的生物合成有明显的显著影响。证据表明，最初的细胞内糖基化步骤和更高的细胞内糖基化步骤之间存在监管差异。莫能菌素不会减少并可能增强最初的合成代谢单糖化和二糖基化，而且似乎还抑制糖鞘糖脂的较高糖基化。
We have exposed cultured human fibroblasts to micromolar concentrations of the ionophore monensin. A salient result was a rapid accumulation in these cells of glucosylceramide (glucocerebroside, GlcCer) and lactosylceramide (lactocerebroside, LacCer). When we incubated these cells with radioactively labeled galactose, GlcCer and LacCer became highly labeled. These results indicate that monensin greatly increases these simplest glycosphingolipids that are the precursor to the major plasma membrane glycosphingolipids. We observed, simultaneously, a decreased incorporation of labeled galactose into some more highly glycosylated neutral glycosphingolipids and sialoglycosphingolipids (gangliosides), and unlike GlcCer and LacCer, the cellular content of these more highly glycosylated compounds remained the same in the presence or absence of monensin. We have found that cultured Gaucher disease fibroblasts, with genetically impaired lysosomal glucocerebrosidase activity, accumulated even more GlcCer and LacCer than normal cells upon exposure to monensin. This finding shows that monensin affects biosynthesis rather than merely disrupting lysosomal degradation that is already deleted with respect to GlcCer in Gaucher disease cells. These results represent the first indication of an apparently remarkable effect of the monovalent ionophore, monensin, on plasma membrane glycosphingolipid biosynthesis. The evidence suggests a regulatory distinction between initial and higher intracellular glycosylation steps. Monensin does not diminish and may augment initial anabolic mono- and diglycosylations and also appears to inhibit higher glycosylations of glycosphingolipids.
离子载体莫能菌素对培养软骨细胞 II 型胶原和蛋白聚糖合成和分泌的影响。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Nishimoto,SK;Kajiwara,T;Ledger,PW;Tanzer,ML
通讯作者：
Tanzer,ML
莫能菌素存在时分泌的人纤连蛋白糖基化异常。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ledger,PW;Nishimoto,SK;Hayashi,S;Tanzer,ML
通讯作者：
Tanzer,ML
莫能菌素抑制大鼠纤维肉瘤细胞中透明质酸的合成。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Goldberg,RL;Toole,BP
通讯作者：
Toole,BP