title: Chondroitin sulfate/dermatan sulfate hybrid chains from embryonic pig brain, which contain a higher proportion of L-iduronic acid than those from adult pig brain, exhibit neuritogenic and growth factor binding activities.
abstract: We have shown that over-sulfated chondroitin sulfate/dermatan sulfate (CS/DS) chains from various marine organisms exhibit growth factor binding activities and neurite outgrowth-promoting activities in embryonic mouse hippocampal neurons in vitro. In this study we demonstrated that CS/DS hybrid chains purified from embryonic pig brain displayed marked neuritogenic activity and growth factor binding activities toward fibroblast growth factor 2 (FGF2), FGF10, FGF18, pleiotrophin, and midkine, all of which exhibit neuroregulatory activities in the brain. In contrast, the CS/DS preparation from adult pig brain showed considerably less activity to bind these growth factors and no neuritogenic activity. Structural analysis indicated that the average size of the CS/DS chains was similar (40 kDa) between these two preparations, but the disaccharide compositions differed considerably, with a significant proportion of l-iduronic acid (IdoUA)-containing disaccharides (8 approximately 9%) in the CS/DS chains from embryos but not in those from adults (<1%). Interestingly, both neurite outgrowth-promoting activity and growth factor binding activities of the CS/DS chains from embryos were abolished by digestion not only with chondroitinase ABC but also with chondroitinase B, suggesting that the IdoUA-containing motifs are essential for these activities. These findings imply that the temporal expression of CS/DS hybrid structures containing both GlcUA and IdoUA and binding activities toward various growth factors play important roles in neurogenesis in the early stages of the development of the brain.
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Japan.
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Bao
authors.forename: Shuji
authors.initials: S
authors.lastname: Nishimura
authors.forename: Tadahisa
authors.initials: T
authors.lastname: Mikami
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Itoh
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D015374:Biosensing Techniques; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003871:Dermatan Sulfate / Q000737:chemistry*; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005965:Glucuronates / Q000737:chemistry; D006133:Growth Substances / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry; D006624:Hippocampus / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007067:Iduronic Acid / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013552:Swine; D013997:Time Factors
chemical_list: D004187:Disaccharides; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D005965:Glucuronates; D006133:Growth Substances; D011993:Recombinant Fusion Proteins; C113569:fibroblast growth factor 18; D016222:Fibroblast Growth Factor 2; D003871:Dermatan Sulfate; D007067:Iduronic Acid; D005346:Fibroblast Growth Factors; D006820:Hyaluronic Acid; D006493:Heparin; D002809:Chondroitin Sulfates