IMPORTANCE OF 6-O-SULFATE GROUPS OF GLUCOSAMINE RESIDUES IN HEPARIN FOR ACTIVATION OF FGF-1 AND FGF-2

IMPORTANCE OF 6-O-SULFATE GROUPS OF GLUCOSAMINE RESIDUES IN HEPARIN FOR ACTIVATION OF FGF-1 AND FGF-2
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DOI:
10.1093/oxfordjournals.jbchem.a125015
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发表时间:
1995-12-01
影响因子:
2.7
通讯作者:
YOSHIDA, K
YOSHIDA, K
中科院分区:
生物学4区
文献类型:
--
作者:
ISHIHARA, M;TAKANO, R;YOSHIDA, K

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为了评价N-硫酸氨基葡萄糖残基中6-O-硫酸酯基团对成纤维细胞生长因子-1和成纤维细胞生长因子-S活性的促进作用,将肝素的吡啶盐与N-甲基三甲基硅基-三氟乙酰胺在不同温度下处理2 h,使三硫代二糖单元发生不同程度的6-O-脱硫化反应,而没有发现解聚或其他化学变化。定量检测了不同的6-O-去硫酸(6-O-DS-)肝素对成纤维细胞生长因子-1和成纤维细胞生长因子-2诱导的BALB/c3T3克隆A31(A31)细胞和氯酸盐处理的细胞增殖的促进或抑制作用。结果表明,激活成纤维细胞生长因子-1需要GlcNS残基中高含量的6-O-硫酸盐基团,而不需要激活成纤维细胞生长因子-2。然而,肝素中三硫代二糖单元的6-O-完全脱除会导致失去激活成纤维细胞生长因子-2的能力,尽管脱硫化产物与成纤维细胞生长因子2结合很强。
Treatment of the pyridinium salts of heparin with N-metlhyltrimethylsilyl-trifluoroacetamide (MTSTFA) in pyridine for 2 h at various temperatures caused specific 6-O-desulfations from trisulfated disaccharide units to various degrees without detectable depolymerization or other chemical changes, In order to assess the importance of 6-O-sulfate groups in N-sulfated glucosamine (GlcNS) residues to promote FGF-1 and FGF-S activities, various 6-O-desulfated (6-O-DS-) heparins were quantitatively examined for activity as enhancers or inhibitors of specific FGF-1- and FGF-2-induced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlorate-treated cells. The present results suggested that a high content of 6-O-sulfate groups in GlcNS residues was required for activation of FGF-1, but not FGF-2, However, complete 6-O-desulfation of trisulfated disaccharide units in heparin resulted in loss of the ability to activate FGF-2, although the desulfated product bound strongly to FGF-2.