Role of Hyaluronidases in the Catabolism of Chondroitin Sulfate

  • Shuhei YamadaEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 842)


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.


Chondroitin sulfate Glycosaminoglycan Hyaluronan Hyaluronidase Hydrolase 







Chondroitin sulfate




d-Glucuronic acid






High performance liquid chromatography



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.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Pathobiochemistry, Faculty of PharmacyMeijo UniversityNagoyaJapan

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