Effect of D-glucosamine on growth and several functions of cultured mastocytoma P-815 cells.
Effect of D-glucosamine on growth and several functions of cultured mastocytoma P-815 cells.
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D-葡萄糖胺对培养的肥大细胞瘤 P-815 细胞生长和多种功能的影响。
DOI：
10.1248/bpb1978.3.577
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
K. Tomita
中科院分区：
文献类型：
--
作者：
A. Ichikawa;M. Takagi;K. Tomita
为了阐明D-氨基葡萄糖对肿瘤细胞选择性细胞毒作用的生化基础，本文研究了D-氨基葡萄糖对肥大细胞瘤P-815细胞生长和某些功能的影响。肥大细胞瘤细胞与5 mM葡萄糖胺孵育导致生长显著抑制，细胞摄取和葡萄糖氧化以及细胞三磷酸腺苷酶（ATP）水平显著降低。氨基葡萄糖还减少了尿苷核苷酸池的大小，并积累了尿苷二磷酸（UDP）-N-乙酰氨基葡萄糖。然而，葡萄糖胺的生长抑制，这是由葡萄糖逆转，不能阻止外源性尿苷。此外，葡糖胺抑制胸苷的磷酸化及其与脱氧核糖核酸（DNA）的结合。葡萄糖胺对细胞分裂的抑制伴随着肥大细胞瘤细胞几种功能的升高，包括腺苷-3 '，5'-单磷酸（cAMP）、组胺和5-羟色胺的积累。[（35）S]SO（4）（2-）掺入酸性糖胺聚糖的量也增加。在这些功能改变中，cAMP水平的升高是最早可检测到的变化，表明肥大细胞瘤细胞的生长和功能也受cAMP调节。然而，葡萄糖胺在体外并不影响质膜腺苷酸环化酶的活性，这表明葡萄糖胺的作用需要完整的膜结构。
In order to elucidate the biochemical basis for the selective cytotoxicity of D-glucosamine to neoplastic cells, the effect of glucosamine on the growth and several functions of mastocytoma P-815 cells were examined. Incubation of mastocytoma cells with 5 mM glucosamine resulted in a marked inhibition of growth and a significant reduction of cellular uptake and oxidation of glucose and of cellular levels of adenosine triphosphatase (ATP). Glucosamine also reduced the uridine nucleotide pool sizes, and accumulated uridine diphosphate (UDP)-N-acetylglucosamine. However, growth inhibition by glucosamine, which was reversed by glucose, was not prevented by exogenous uridine. In addition, glucosamine suppressed the phosphorylation of thymidine and its incorporation into deoxyribonucleic acid (DNA). The suppression of cell division by glucosamine was accompanied by the elevation of several functions of mastocytoma cells, including the accumulation of adenosine-3', 5'-monophosphate (cAMP), histamine, and serotonin. The incorporation of [(35)S]SO(4)(2-) into acidic glycosaminoglycan was also increased. Of these functional alterations, the elevation of cAMP levels was the earliest detectable change, indicating that growth and functions of mastocytoma cells are also regulated by cAMP. However, glucosamine did not affect the adenylate cyclase activity of plasma membrane in vitro, suggesting the necessity of intact membrane structure for the action of glucosamine.