Chondroitin Hydrolase in Caenorhabditis elegans

Abstract

At the initial stage of cellular degradation of chondroitin sulfate/dermatan sulfate, an endo-type hydrolase is thought to degrade the long chain polysaccharides. Thus far, no endoglycosidases that are speciˆc for chondroitin sulfate/dermatan sulfate have been reported; however, hyaluronan-degrading enzymes, hyaluronidases, are considered responsible. The nematode, Caenorhabditis elegans, is an ideal model for studies in a wide range of fundamental biological disciplines. Studies using the nematode have elucidated the biosynthetic mechanisms and functions of glycosaminoglycans. However, the catabolic pathways for glycosaminoglycans in C. elegans have not been investigated. Since C. elegans contains nonsulfated chondroitin but no hyaluronan, it is an ideal system for studying the hyaluronidase-independent catabolic mechanism of chondroitin/chondroitin sulfate. We have identiˆed a chondroitin-speciˆc endo-type hydrolase in C. elegans for theˆrst time. The discovery of this enzyme suggests the presence of chondroitin sulfate/dermatan sulfate-speciˆc endoglycosidases in mammalian systems.

Hyaluronidases Have Strong Hydrolytic Activity toward Chondroitin 4-Sulfate Comparable to that for Hyaluronan

“…Therefore, we have sought a CS-specific endo-type hydrolase [24,25], and demonstrated HYAL4 to be a CS-specific hydrolase [10,11]. However, the expression of human HYAL4 is not ubiquitous but restricted to the placenta, skeletal muscle, and testis [12,13].…”

“…The genuine substrate of hyaluronidases has been considered to be HA, although the enzymes also depolymerize CS, because HYAL1 was reported to digest CS more slowly than HA [ 8 , 9 ]. Therefore, we have sought a CS-specific endo-type hydrolase [ 24 , 25 ], and demonstrated HYAL4 to be a CS-specific hydrolase [ 10 , 11 ]. However, the expression of human HYAL4 is not ubiquitous but restricted to the placenta, skeletal muscle, and testis [ 12 , 13 ].…”