MODULATION OF CELL-SURFACE HEPARAN-SULFATE STRUCTURE BY GROWTH OF CELLS IN THE PRESENCE OF CHLORATE
MODULATION OF CELL-SURFACE HEPARAN-SULFATE STRUCTURE BY GROWTH OF CELLS IN THE PRESENCE OF CHLORATE
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DOI：
10.1021/bi00446a021
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发表时间：
1989-10-03
期刊：
影响因子：
2.9
通讯作者：
KELLER, JM
中科院分区：
文献类型：
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作者：
KELLER, KM;BRAUER, PR;KELLER, JM
瑞士小鼠3 T3细胞，当在5 mM氯酸盐（PAPS合成的抑制剂）存在下生长时，产生硫酸乙酰肝素糖胺聚糖链，其仅含有约8%的通常存在的硫酸盐，并且其已经失去了与纤连蛋白结合的能力。这些未充分硫酸化的链在pH 4.5下对亚硝酸敏感，表明许多葡糖胺基残基具有未取代的氨基。在氯酸盐存在下产生的硫酸乙酰肝素的艾杜糖醛酸含量降低至小于7%，相比之下，来自未处理细胞的艾杜糖醛酸含量为36%。氯酸盐处理的细胞在其生长控制中未表现出任何改变。然而，与未处理细胞的更典型的成纤维细胞外观相比，这些细胞的铺展行为改变为扁平圆形形态。软骨素链的硫酸化也被抑制，但在较低的氯酸盐浓度下，这不会改变细胞的生长控制或扩散能力。这些数据表明（a）3 T3细胞表面硫酸乙酰肝素蛋白聚糖不参与生长控制，但可能参与细胞铺展，（B）氯酸盐的使用应该是研究硫酸化糖胺聚糖的生物合成和结构/功能关系的有价值的方法，和（c）从无细胞提取物的研究结果预测的硫酸乙酰肝素链修饰反应的时间顺序也在细胞中起作用。
Swiss mouse 3T3 cells, when grown in the presence of 5 mM chlorate, an inhibitor of PAPS synthesis, produce heparan sulfate glycosaminoglycan chains containing only about 8% of the sulfate normally present and which have lost the ability to bind to fibronectin. These undersulfated chains are sensitive to nitrous acid at pH 4.5, indicating that many glucosaminyl residues have unsubstituted amino groups. The iduronic acid content of the heparan sulfate produced in the presence of chlorate is reduced to less than 7% as compared to the 36% in that from untreated cells. The chlorate-treated cells do not demonstrate any alterations in their growth control. However, the spreading behavior of these cells is altered to a flat rounded morphology compared to the more typical fibroblastic appearance of the untreated cell. The sulfation of chondroitin chains is also inhibited, but at a lower chlorate concentration which does not alter growth control or the spreading ability of the cells. These data indicate that (a) 3T3 cell surface heparan sulfate proteoglycan is not involved in growth control but may be involved in cell spreading, (b) the use of chlorate should be a valuable method for the study of the biosynthesis and structure/function relationships of sulfated glycosaminoglycans, and (c) the temporal sequence of the heparan sulfate chain modification reactions predicted from results of studies with cell-free extracts also operates in the cell.