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Glycoconjugate Journal

, Volume 30, Issue 6, pp 619–632 | Cite as

Interaction of chondroitin sulfate and dermatan sulfate from various biological sources with heparin-binding growth factors and cytokines

  • Shuji Mizumoto
  • Duriya Fongmoon
  • Kazuyuki SugaharaEmail author
Article

Abstract

Chondroitin sulfate (CS) and dermatan sulfate (DS) interact with various extracellular molecules such as growth factors, cytokines/chemokines, neurotrophic factors, morphogens, and viral proteins, thereby playing roles in a variety of biological processes including cell adhesion, proliferation, tissue morphogenesis, neurite outgrowth, infections, and inflammation/leukocyte trafficking. CS/DS are modified with sulfate groups at C-2 of uronic acid residues as well as C-4 and/or C-6 of N-acetyl-D-galactosamine residues, yielding enormous structural diversity, which enables the binding with numerous proteins. We have demonstrated that highly sulfated CS-E from squid cartilage, for example, interacts with heparin-binding proteins including midkine, pleiotrophin, and fibroblast growth factors expressed in brain with high affinity (Kd values in the nM range). Here, we analyzed the binding of CS and DS, which have a relatively low degree of sulfation and have been widely used as a nutraceutical and a drug for osteoarthritis etc., with a number of heparin-binding neurotrophic factors/cytokines using surface plasmon resonance (SPR) and structurally characterized the CS/DS chains. SPR showed that relatively low sulfated CS-A, DS, and CS-C also bound with significant affinity to midkine, pleiotrophin, hepatocyte growth factor, monokine-induced by interferon-γ, and stromal cell derived factor-1β, although the binding was less intense than that with highly sulfated CS-D and CS-E. These findings suggest that even low sulfated CS and/or DS chains may contain binding domains, which include fine sugar sequences with specific sulfation patterns, and that sugar sequences, conformations and electrostatic potential are more important than the simple degree of sulfation represented by disaccharide composition.

Keywords

Chondroitin sulfate Dermatan sulfate Growth factors Cytokines Interaction analysis Surface plasmon resonance 

Abbreviations

CS

Chondroitin sulfate

DS

Dermatan sulfate

FGF

Fibroblast growth factor

GAG

Glycosaminoglycan

HIV

Human immunodeficiency virus

HGF

Hepatocyte growth factor

MIG

Monokine-induced by interferon-γ

MK

Midkine

PG

Proteoglycan

PTN

Pleiotrophin

RANTES

Regulated upon activation normal T cell express sequence

SDB-1β

Stromal cell derived factor-1β

SPR

Surface plasmon resonance

Notes

Acknowledgments

This work was supported in part by Grants-in-aid for Scientific Research on Innovative Areas (24110501) (to K.S.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT), Japan–Thailand Research Cooperative Program (to K. S.), Young Scientists (B) 23790066 (to S. M.) from the Japan Society for the Promotion of Science (JSPS), and the endowment from Zeria Pharmaceutical Co., Ltd.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Shuji Mizumoto
    • 1
  • Duriya Fongmoon
    • 1
    • 2
  • Kazuyuki Sugahara
    • 1
    Email author
  1. 1.Laboratory of Proteoglycan Signaling and Therapeutics, Frontier Research Center for Post-Genomic Science and TechnologyHokkaido University Graduate School of Life ScienceSapporoJapan
  2. 2.Department of Medical Services, Ministry of Public HealthThe Lampang Cancer HospitalLampangThailand

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