Selective activation of heparin cofactor II by a sulfated polysaccharide isolated from the leaves of Artemisia princeps

Selective activation of heparin cofactor II by a sulfated polysaccharide isolated from the leaves of Artemisia princeps
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从蒿叶中分离出的硫酸化多糖选择性激活肝素辅因子 II

DOI:
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发表时间:
1995
影响因子:
1.1
通讯作者:
N. Sakuragawa
N. Sakuragawa
中科院分区:
医学4区
文献类型:
--
作者:
Y. Hayakawa;Toshimitsu Hayashi;T. Hayashi;K. Niiya;N. Sakuragawa

文献摘要

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在检测瓦坎草(Wakan-Yakus)粗提物抗凝血活性的同时,我们检测了青蒿叶多糖部位的抗凝血酶活性。通过DEAE-纤维素离子交换层析和Sepharose6B凝胶过滤从粗提物中分离得到一种硫酸多糖,它能增强肝素辅因子II(HC II)依赖的抗凝血酶活性,但不能增强AT III(AT III)的抗凝血酶活性。该多糖可使HC II-凝血酶反应增强6000倍以上。在2 5~12 5μ/ml浓度范围内,HC II抑制凝血酶的表观二级速率常数由3.8×10 4(无多糖时)增加到2 3×10 8M-1min-1。在人血浆中,该多糖可加速凝血酶-HC II复合体的形成。软骨素酶AC I、肝素酶或肝素酶对HC II依赖的抗凝血酶活性的刺激作用几乎完全消失,而软骨素酶ABC或软骨素酶AC II几乎不起作用。这些结果表明,该多糖是一种糖胺多糖样物质,其性质与肝素或硫酸皮肤素截然不同。
While checking anticoagulant activities in crude fractions from Wakan-Yakus (traditional herbal drugs), we detected antithrombin activity in the polysaccharide fraction of the leaves of Artemisia princeps Pamp. A sulfated polysaccharide purified from the crude fractions by ion-exchange chromatography on DEAE-cellulose and gel filtration on Sepharose 6B potentiated the heparin cofactor II (HC II)-dependent antithrombin activity but not the antithrombin activity of antithrombin III (AT III). The polysaccharide enhanced the HC II-thrombin reaction more than 6000-fold. The apparent second-order rate constant of thrombin inhibition by HC II increased from 3.8 × 104 (in the absence of the polysaccharide) to 23 × 108 M-1 min-1 in the presence of 25–125 μ/ml of the polysaccharide. In human plasma, the poly saccharide accelerated the formation of thrombin—HC II complex. The stimulating effect on HC II-dependent antithrombin activity was almost totally abolished by treatment with chondroitinase AC I, heparinase or heparitinase, while chondroitinase ABC or chondroitinase AC II had little or no effect. These results suggest that the polysaccharide is a glycosaminoglycan-like material with properties that are quite distinct from heparin or dermatan sulfate.