Skip to main content

Role of Hyaluronidases in the Catabolism of Chondroitin Sulfate

  • Conference paper
  • First Online:
Biochemical Roles of Eukaryotic Cell Surface Macromolecules

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 842))

Abstract

Chondroitin sulfate (CS) is widely distributed as the glycosaminoglycan side chain of proteoglycans in extracellular matrices and at cell surfaces. The mechanism underlying the catabolism of CS has yet to be elucidated in detail. We recently identified hyaluronidase-4 (HYAL4) as a CS-specific endo-β-N-acetylgalactosaminidase for the first time. However, the expression of HYAL4 mRNA was not ubiquitous but restricted to the placenta, skeletal muscle, and testis. These findings suggested that HYAL4 may not be involved in the systemic catabolism of CS, but rather has specific functions in particular organs or tissues. Of the hyaluronidase family members, hyaluronidase-1 (HYAL1) is known to be ubiquitously expressed and can degrade CS chains, although its activity toward CS was previously shown to be limited. Its preferred substrate was suggested to be HA, not CS. However, to the best of our knowledge, no quantitative comparison of the hydrolytic activities of hyaluronidases toward CS and HA has been performed to date. Therefore, a new method was developed to determine glycosaminoglycan-hydrolyzing activity with high sensitivity, and we measured and compared the hydrolytic activity of hyal1 towards CS variants as well as HA. We found that HYAL1 hydrolyzed CS-A more rapidly than HA. Based on the appearance of CS prior to HA during evolution, hyaluronidases may originally have been CS hydrolases that subsequently acquired hydrolytic activity toward HA. Thus, hyaluronidases appear to recognize CS chains as their primary substrate and play a role in various biological processes by degrading CS chains.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

2AB:

2-Aminobenzamide

Chn:

Chondroitin

CS:

Chondroitin sulfate

GalNAc:

N-Acetyl-d-galactosamine

GlcUA:

d-Glucuronic acid

GPI:

Glycosylphosphatidylinositol

HA:

Hyaluronan

HPLC:

High performance liquid chromatography

References

  • Chao KL, Muthukumar L, Herzberg O (2007) Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis. Biochemistry 46:6911–6920

    Article  CAS  Google Scholar 

  • Csoka AB, Frost GI, Stern R (2001) The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol 20:499–508

    Article  CAS  Google Scholar 

  • Esko JD, Selleck SB (2002) Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem 71:435–471

    Article  CAS  Google Scholar 

  • Gushulak L, Hemming R, Martin D, Seyrantepe V, Pshezhetsky A, Triggs-Raine B (2012) Hyaluronidase 1 and β-exosaminidase have redundant functions in hyaluronan and chondroitin sulfate degradation. J Biol Chem 287:16689–16697

    Article  CAS  Google Scholar 

  • Honda T, Kaneiwa T, Mizumoto S, Sugahara K, Yamada S (2012) Hyaluronidases have strong hydrolytic activity toward chondroitin 4-sulfate comparable to that for hyaluronan. Biomolecules 2:549–563

    Article  CAS  Google Scholar 

  • Iozzo RV (1998) Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem 67:609–652

    Article  CAS  Google Scholar 

  • Jedrzejas MJ, Stern R (2005) Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis. Proteins 61:227–238

    Article  CAS  Google Scholar 

  • Kaneiwa T, Yamada S, Mizumoto S, Montaño AM, Mitani S, Sugahara K (2008) Identification of a novel chondroitin hydrolase in Caenorhabditis elegans. J Biol Chem 283:14971–14979

    Article  CAS  Google Scholar 

  • Kaneiwa T, Mizumoto S, Sugahara K, Yamada S (2010) Identification of human hyaluronidase-4 as a novel chondroitin sulfate hydrolase that preferentially cleaves the galactosaminidic linkage in the trisulfated tetrasaccharide sequence. Glycobiology 20:300–309

    Article  CAS  Google Scholar 

  • Kaneiwa T, Miyazaki A, Kogawa R, Mizumoto S, Sugahara K, Yamada S (2012) Identification of amino acid residues required for the substrate specificity of human and mouse chondroitin sulfate hydrolase (conventional hyaluronidase-4). J Biol Chem 287:42119–42128

    Article  CAS  Google Scholar 

  • Marković-Housley Z, Miglierini G, Soldatova L, Rizkallah PJ, Müller U, Schirmer T (2000) Crystal structure of hyaluronidase, a major allergen of bee venom. Structure 8:1025–1035

    Article  Google Scholar 

  • Mikami T, Koyama S, Yabuta Y, Kitagawa H (2012) Chondroitin sulfate is a crucial determinant for skeletal muscle development/regeneration and improvement of muscular dystrophies. J Biol Chem 287:38531–38542

    Article  CAS  Google Scholar 

  • Prabhakar V, Sasisekharan R (2006) The biosynthesis and catabolism of galactosaminoglycans. Adv Pharmacol 53:69–115

    Article  CAS  Google Scholar 

  • Rauch U, Kappler L (2006) Chondroitin/dermatan sulfates in the central nervous system: their structures and functions in health and disease. Adv Pharmacol 53:337–356

    Article  CAS  Google Scholar 

  • Rodén L (1980) Structure and metabolism of connective tissue proteoglycans. In: Lennarz WJ (ed) The biochemistry of glycoproteins and proteoglycans. Plenum Publishing Corp, New York, pp 267–371

    Chapter  Google Scholar 

  • Stern R (2008) Hyaluronidases in cancer biology. Semin Cancer Biol 18:275–280

    Article  CAS  Google Scholar 

  • Sugahara K, Yamada S (2000) Structure and function of oversulfated chondroitin sulfate variants: unique sulfation patterns and neuroregulatory activities. Trends Glycosci Glycotechnol 12:321–349

    Article  CAS  Google Scholar 

  • Sugahara K, Mikami T, Uyama T, Mizuguchi S, Nomura K, Kitagawa H (2003) Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate. Curr Opin Struct Biol 13:612–620

    Article  CAS  Google Scholar 

  • Sugahara KN, Hirata T, Tanaka T, Ogino S, Takeda M, Shimada I, Tamura J, ten Dam GB, van Kuppevelt TH, Miyasaka M (2008) Chondroitin sulfate E fragments enhance CD44 cleavage and CD44-dependent motility in tumor cells. Cancer Res 68:7191–7199

    Article  CAS  Google Scholar 

  • Uyama T, Kitagawa H, Sugahara K (2007) Biosynthesis of glycosaminoglycans and proteoglycans. In: Kamerling JP (ed) Comprehensive glycoscience, vol 3. Elsevier, Amsterdam, pp 79–104

    Chapter  Google Scholar 

  • Yamada S, Sugahara K (2008) Potential therapeutic application of chondroitin sulfate/dermatan sulfate. Curr Drug Discov Technol 5:289–301

    Article  CAS  Google Scholar 

  • Yamada S, Van Die I, Van den Eijnden DH, Yokota A, Kitagawa H, Sugahara K (1999) Demonstration of glycosaminoglycans in Caenorhabditis elegans. FEBS Lett 459:327–331

    Article  CAS  Google Scholar 

  • Yamada S, Okada Y, Ueno M, Iwata S, Deepa SS, Nishimura S, Fujita M, Van Die I, Hirabayashi Y, Sugahara K (2002) Determination of the glycosaminoglycan-protein linkage region oligosaccharide structures of proteoglycans from Drosophila melanogaster and Caenorhabditis elegans. J Biol Chem 277:31877–31886

    Article  CAS  Google Scholar 

  • Yamada S, Morimoto H, Fujisawa T, Sugahara K (2007) Glycosaminoglycans in Hydra magnipapillata (Hydrozoa, Cnidaria): demonstration of chondroitin in the developing nematocyst, sting organelle, and structural characterization of glycosaminoglycans. Glycobiology 17:886–894

    Article  CAS  Google Scholar 

  • Yamada S, Mizumoto S, Sugahara K (2009a) Chondroitin hydrolase in Caenorhabditis elegans. Trends Glycosci Glycotechnol 21:149–162

    Article  CAS  Google Scholar 

  • Yamada S, Onishi M, Fujinawa R, Tadokoro Y, Okabayashi K, Asashima M, Sugahara K (2009b) Structural and functional changes of sulfated glycosaminoglycans in Xenopus laevis during embryogenesis. Glycobiology 19:488–498

    Article  CAS  Google Scholar 

  • Yamada S, Sugahara K, Özbek S (2011) Evolution of glycosaminoglycans: comparative biochemical study. Commun Integr Biol 4:150–158

    Article  CAS  Google Scholar 

  • Yoshida H, Nagaoka A, Kusaka-Kikushima A, Tobiishi M, Kawabata K, Sayo T, Sakai S, Sugiyama Y, Enomoto H, Okada Y, Inoue S (2013) KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization. Proc Natl Acad Sci U S A 110:5612–5617

    Article  CAS  Google Scholar 

  • Zhang L, Bharadwaj AG, Casper A, Barkley J, Barycki JJ, Simpson MA (2009) Hyaluronidase activity of human Hyal1 requires active site acidic and tyrosine residues. J Biol Chem 284:9433–9442

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Grants-in-aid for Scientific Research (C) (24590071) and for Scientific Research on Innovative Areas (26110719) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT), and the Research Institute of Meijo University, Japan. I thank Professor Kazuyuki Sugahara (Hokkaido University) for his helpful suggestions as well as Tomoko Honda, Tomoyuki Kaneiwa, and Shuji Mizumoto (Hokkaido University) for their substantial contribution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shuhei Yamada .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this paper

Cite this paper

Yamada, S. (2015). Role of Hyaluronidases in the Catabolism of Chondroitin Sulfate. In: Chakrabarti, A., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 842. Springer, Cham. https://doi.org/10.1007/978-3-319-11280-0_12

Download citation

Publish with us

Policies and ethics