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.
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.
Bao
Xingfeng
X
Department of Biochemistry, Kobe Pharmaceutical University, Japan.
Nishimura
Shuji
S
Mikami
Tadahisa
T
Yamada
Shuhei
S
Itoh
Nobuyuki
N
Sugahara
Kazuyuki
K
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
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