Shetty Ajaya Kumar, Kobayashi Takanari, Mizumoto Shuji, Narumi Masaki, Kudo Yoshiaki, Yamada Shuhei, Sugahara Kazuyuki
Laboratory of Proteoglycan Signaling and Therapeutics, Hokkaido University, Graduate School of Life Science, Kita-ku, Sapporo 001-0021, Japan.
Carbohydr Res. 2009 Aug 17;344(12):1526-32. doi: 10.1016/j.carres.2009.02.029. Epub 2009 Mar 5.
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.
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。