神経突起伸長と血管新生におけるグリコサミノグリカン糖鎖の分子認識

1)在从新生小鼠脑中提纯的硫酸软骨素制剂中发现了所谓的D二糖单位。商品鲨鱼软骨硫酸软骨素D制剂具有促进神经突起生长的活性。2)商品鱿鱼软骨硫酸软骨素E制剂对培养的胚胎大鼠脑神经细胞具有促突起生长活性。进一步证明，硫酸软骨素E制剂可以结合中期因子并抑制中期因子介导的神经细胞与培养底物的黏附。3)肿瘤来源的黏附因子，血管调节蛋白，促进向培养的人肿瘤细胞系ECV304形成脐带，并被认为与肿瘤血管生成有关。4)硫酸软骨素链的硫酸盐化和硫酸转移酶活性在胚胎发育和新生鸡的生长过程中受到调节。5)参与糖胺-蛋白质连接区四糖序列合成的葡萄糖醛酸基转移酶被分子克隆，并对其性质进行了表征。6)一个截短的四糖片段Glca-Gal-Gal-Xyl，它与糖胺聚糖-蛋白连接区的连接区相对应从人肉瘤细胞系培养上清液中纯化的α-血栓调节蛋白-α-GalNAc转移酶与肿瘤抑制基因Ext基因家族的ExTL2基因编码的ExTL2蛋白完全相同，并且具有启动和决定硫酸乙酰肝素合成的α-GlcNAc转移酶活性。

1) The so-called D disaccharide unit was demonstrated in the chondroitin sulfate preparation purified from neonatal mouse brains. Neurite outgrowth promoting activity was also demonstrated for the commercial shark cartilage chondroitin sulfate D preparation which contained a high proportion of the D disaccharide unit.2) It was demonstrated that the commercial squid cartilage chondroitin sulfate E preparation had neurite outgrowth promoting activity toward cultured neuronal cells derived from embryonic rat brains. The chondroitin sulfate E preparation was further demonstrated to bind midkine and inhibit the midkine-mediated neuronal cell adhesion to the culture substrate.3) The tumor-derived adhesion factor, angiomodulin, promotes the cord formation towards the cultured human tumor cell line ECV304, and has been proposed to be associated with tumor angiogenesis. The angiomodulin-binding domain on heparan sulfate chains was shown to be larger than dodecasaccharides and highly sulfated.4) Sulfation of the chondroitin sulfate chains and sulfotransferase activities in embryonic chick brains were shown to be regulated during embryonic development and neonatal growth.5) Glucuronyltransferase that is involved in the synthesis of the glycosaminoglycan-protein linkage region tetrasaccharide sequence, GlcA-Gal-Gal-Xyl, was molecularly cloned and its properties were characterized.6) A truncated tetrasaccharide fragment, GlcA-Gal-Gal-Xyl, which corresponded to the glycosaminoglycan-protein linkage region, was demonstrated on a part-time proteoglycan, α-thrombomodulin.7) α-GalNAc transferase purified from the culture medium of a human sarcoma cell line was shown to be identical with the EXTL2 protein encoded by the EXTL2 gene, which belonged to the tumor suppressor EXT gene family, and to harbor the α-GlcNAc transferase activity that initiates and determines the heparan sulfate synthesis.