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从富含N-乙酰半乳糖胺(4,6-二硫酸酯)和葡萄糖醛酸(3-硫酸酯)残基的鱿鱼肝脏外皮中分离并鉴定一种新型硫酸软骨素。

Isolation and characterization of a novel chondroitin sulfate from squid liver integument rich in N-acetylgalactosamine(4,6-disulfate) and glucuronate(3-sulfate) residues.

作者信息

Shetty Ajaya Kumar, Kobayashi Takanari, Mizumoto Shuji, Narumi Masaki, Kudo Yoshiaki, Yamada Shuhei, Sugahara Kazuyuki

机构信息

Laboratory of Proteoglycan Signaling and Therapeutics, Hokkaido University, Graduate School of Life Science, Kita-ku, Sapporo 001-0021, Japan.

出版信息

Carbohydr Res. 2009 Aug 17;344(12):1526-32. doi: 10.1016/j.carres.2009.02.029. Epub 2009 Mar 5.

Abstract

Novel chondroitin sulfate (CS) chains with an average molecular mass of 79.6 kDa were purified from squid liver integument. A compositional analysis of the CS chains using chondroitinases (CSases) ABC and AC-I revealed a range of variably sulfated disaccharides with GlcAbeta1-->3GalNAc(6-sulfate), GlcAbeta1-->3GalNAc(4-sulfate), and GlcAbeta1-->3GalNAc(4,6-disulfate) as the major ones, significant amounts of rare 3-sulfated GlcA-containing disaccharides, and a small amount of nonsulfated GlcAbeta1-->3GalNAc. The CS chains exhibited neurite outgrowth-promoting activity toward embryonic mouse hippocampal neurons, which was abolished completely by digestion with CSase ABC or AC-I. Consequently, whether these CS chains interact with heparin-binding growth factors was tested in a BIAcore system. All of the growth factors exhibited concentration-dependent and specific binding. CS chains from squid liver integument, with their unique composition and strong biological activities, may be a good candidate for therapeutic application.

摘要

从鱿鱼肝脏外皮中纯化出平均分子量为79.6 kDa的新型硫酸软骨素(CS)链。使用软骨素酶(CSases)ABC和AC-I对CS链进行的组成分析显示,一系列硫酸化程度不同的二糖中,主要的有β1,3-连接的葡萄糖醛酸(GlcA)与N-乙酰半乳糖胺(GalNAc)(6-硫酸化)、GlcAβ1→3GalNAc(4-硫酸化)和GlcAβ1→3GalNAc(4,6-二硫酸化),还有大量含罕见3-硫酸化GlcA的二糖以及少量非硫酸化的GlcAβ1→3GalNAc。这些CS链对胚胎小鼠海马神经元表现出促进神经突生长的活性,而用CSase ABC或AC-I消化后该活性完全消失。因此,在BIAcore系统中测试了这些CS链是否与肝素结合生长因子相互作用。所有生长因子均表现出浓度依赖性和特异性结合。鱿鱼肝脏外皮中的CS链具有独特的组成和强大的生物活性,可能是治疗应用的良好候选物。

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