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不同结构硫酸软骨素对白血病细胞的影响:U-937细胞的增殖与分化

Effects of chondroitin sulfates with different structures on leukemia cells: U-937 cell proliferation and differentiation.

作者信息

Volpi N, Bolognani L, Conte A, Petrini M

机构信息

Department of Biologia Animale, University of Modena, Italy.

出版信息

Leuk Res. 1993 Sep;17(9):789-98. doi: 10.1016/0145-2126(93)90114-z.

DOI:10.1016/0145-2126(93)90114-z
PMID:7690435
Abstract

Chondroitin sulfates extracted and purified by different manufacturers were tested to evaluate their effects on proliferation and differentiation processes of U-937 cells. The different chondroitin sulfates were evaluated for purity, structure and physicochemical properties. The three chondroitin sulfates utilized did not present other contaminant glycosaminoglycans and proteins and had about the same relative molecular mass but different disaccharide patterns and charge density. Chondroitin sulfates with small amounts of disulfated disaccharides and low charge density, at 5 micrograms/ml concentration, doubled (about + 133%) cell proliferation in comparison to controls. In contrast, chondroitin sulfates with large amounts of disulfated disaccharides and high sulfate to carboxyl ratio were less effective (about + 15%) in stimulating cell proliferation at low concentration. A decrease of U-937 cell proliferation was observed in proportion to the increased amounts of chondroitin sulfate with low sulfate to carboxyl ratio. On the contrary, chondroitin sulfate with large amounts of disulfated disaccharides produced increased cell proliferation depending on concentration. Small amounts (5-10 micrograms/ml) of chondroitin sulfates with low charge density reduced the differentiative process of U-937 cells. Chondroitin sulfate with large amounts of disulfated disaccharides and high charge density seemed to be able to produce a significant decrease of differentiative processes only at very high concentrations (1000 micrograms/ml). These contrasting effects of chondroitin sulfates with different disaccharide patterns (and structure) and charge density on a leukemia cell line could help to explain the regulation of proliferative and/or differentiative processes of hemopoietic cells. This is underlined by the changes of types, physicochemical properties and structure of glycosaminoglycans induced by different extracellular factors and agents.

摘要

对不同制造商提取和纯化的硫酸软骨素进行了测试,以评估它们对U - 937细胞增殖和分化过程的影响。对不同的硫酸软骨素进行了纯度、结构和物理化学性质评估。所使用的三种硫酸软骨素未呈现其他污染性糖胺聚糖和蛋白质,且相对分子质量大致相同,但二糖模式和电荷密度不同。含少量双硫酸化二糖且电荷密度低的硫酸软骨素,在浓度为5微克/毫升时,与对照组相比使细胞增殖增加了一倍(约 + 133%)。相比之下,含大量双硫酸化二糖且硫酸与羧基比例高的硫酸软骨素在低浓度时刺激细胞增殖的效果较差(约 + 15%)。观察到随着硫酸与羧基比例低的硫酸软骨素含量增加,U - 937细胞增殖减少。相反,含大量双硫酸化二糖的硫酸软骨素根据浓度不同使细胞增殖增加。少量(5 - 10微克/毫升)电荷密度低的硫酸软骨素会降低U - 937细胞的分化过程。含大量双硫酸化二糖且电荷密度高的硫酸软骨素似乎仅在非常高的浓度(1000微克/毫升)时才会使分化过程显著降低。不同二糖模式(和结构)及电荷密度的硫酸软骨素对白血病细胞系的这些相反作用,可能有助于解释造血细胞增殖和/或分化过程的调节。不同细胞外因子和试剂诱导的糖胺聚糖的类型、物理化学性质和结构变化突出了这一点。

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