Identification of biologically active domains of neuroglycan C that can be applicable to repair of brain injuries

鉴定可用于修复脑损伤的神经聚糖 C 的生物活性结构域

基本信息

批准号：
14370449
负责人：
OOHIRA Atsuhiko
金额：
$ 6.78万
依托单位：
Institute for Developmental Research, Aichi Human Service Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

The purpose of this project is identification of biologically active domains of neuroglycan C (NGC), a brain-specific transmembrane chondroitin sulfate proteoglycan. The major results obtained are as follows.1. A single EGF-like module exists in the ectodomain of the NGC core protein. A recombinant peptide containing the EGF-like module promoted phosphorylation of EGF-receptors, ErbB2 and ErbB3, and proliferation of cell lines that express all of four EGF-receptors, indicating that NGC is a novel member of the EGF family.2. A recombinant NGC ectodomain promoted neurite elongation from neocortical neurons in culture. Inhibitors of phosphatidylinositol 3-kinase and of protein kinase C prevented NGC-mediated neurite elongation. The active sites for promotion of neurite elongation existed on the acidic domain and the EGF-like domain of the NGC ectodomain.3. NGC bore achondroitin sulfate (CS) side chain only at Ser-123 on the core protein. NGC isolated from postnatal day-10 rat brains had a relatively high content of E-disaccharide units, an oversulfated CS disaccharide unit, compared with neurocan and phosphacan.4. CS-E, a commercial preparation of highly sulfated CS, promoted FGF-2-mediated proliferation of neural stem cells. To identify the minimum size of CS-E-derived oligosaccharides that have a promotive activity for neural stem cell growth, CS-E was partially degraded, and activities of the degradation products with different molecular sizes were determined. A fraction of 3 kDa (〜12 sugars) showed a strong activity for promotion of neural stem cell proliferation. Quartz-crystal microbalance method revealed that both the 3 kDa fraction and a hexasulfated hexasaccharide had a high affinity to FGF-2,but the latter did not have the promotive activity for cell proliferation.Thus, the EGF-like domain of the NGC core protein and a 3 kDa oligosaccharide derived from E-unit-rich CS have properties that can be applicable to repair of brain injuries.

该oteoglycan的目的如下。1。所有EGF受体中的所有，表明NGC是EGF家族的一个NO成员。2培养物中的重组神经化神经元。单位是一种过度硫化的CS二糖单位，CS-E是高度硫化CS的商业制剂，促进了FGF-2介导的神经干细胞的介导的含量。确定神经干细胞的生长ZE的比例为3 kDa（-22糖），在促进神经干细胞增殖的活性很强。 2 TTER没有细胞泛滥的促进活性。因此，从富含E-UNIT的CS得出的NGC核心蛋白和3 kDa寡糖的EGF样域具有可用于修复脑损伤的特性。