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乙醇会损害培养的大鼠星形胶质细胞中的单糖摄取和糖基化作用。

Ethanol impairs monosaccharide uptake and glycosylation in cultured rat astrocytes.

作者信息

Tomás M, Fornas E, Megías L, Durán J-M, Portolés M, Guerri C, Egea G, Renau-Piqueras J

机构信息

Centro de Investigación, Department of Biology and Cellular Pathology, Hospital Universitario La Fe, Avda. Campenar 21, E-46009 Valencia, Spain.

出版信息

J Neurochem. 2002 Nov;83(3):601-12. doi: 10.1046/j.1471-4159.2002.01167.x.

Abstract

Astrocyte and glial-neuron interactions have a critical role in brain development, which is partially mediated by glycoproteins, including adhesion molecules and growth factors. Ethanol affects the synthesis, intracellular transport, subcellular distribution and secretion of these glycoproteins, suggesting alterations in glycosylation. We analyzed the effect of long-term exposure to low doses of ethanol (30 mm) on glycosylation process in growing cultured astrocytes in vitro. Cells were incubated for short (5 min) and long (90 min) periods with several radioactively labeled carbohydrate precursors. The uptake, kinetics and metabolism of these precursors, as well as the radioactivity distribution in protein gels were analyzed. The levels of GLUT1 and mannosidase II were also determined. Ethanol increased the uptake of monosaccharides and the protein levels of GLUT1 but decreased those of mannosidase II. It altered the carbohydrate moiety of proteins and increased cell surface glycoproteins containing terminal non-reduced mannose. These results indicate that ethanol impairs glycosylation in rat astrocytes, thus disrupting brain development.

摘要

星形胶质细胞与神经胶质-神经元的相互作用在大脑发育中起着关键作用,这一过程部分由糖蛋白介导,包括黏附分子和生长因子。乙醇会影响这些糖蛋白的合成、细胞内运输、亚细胞分布和分泌,提示糖基化发生改变。我们分析了长期暴露于低剂量乙醇(30 mM)对体外培养的生长中的星形胶质细胞糖基化过程的影响。用几种放射性标记的碳水化合物前体对细胞进行短时间(5分钟)和长时间(90分钟)孵育。分析了这些前体的摄取、动力学和代谢,以及蛋白质凝胶中的放射性分布。还测定了葡萄糖转运蛋白1(GLUT1)和甘露糖苷酶II的水平。乙醇增加了单糖的摄取和GLUT1的蛋白质水平,但降低了甘露糖苷酶II的水平。它改变了蛋白质的碳水化合物部分,并增加了含有末端非还原甘露糖的细胞表面糖蛋白。这些结果表明,乙醇损害大鼠星形胶质细胞的糖基化,从而破坏大脑发育。

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