ABSTRACT
Hyaluronan (HA) is a glycosaminoglycan (GAG) widely distributed in vertebrate tissues. Due to its unique biophysicochemical properties, it is involved in many biological processes under both normal and pathological conditions. In addition, HA and its derivatives are used in various medical and aesthetic applications. However, the biophysicochemical properties and biological functions of HA strongly depend on its chain size. By catalyzing HA hydrolysis hyaluronidases (HAases) play an important role in the control of the HA chain size. Our study of the kinetics of the HA hydrolysis catalyzed by HAase led us to the conclusion that two phenomena should be taken into account to properly describe the behavior of the hyaluronan/hyaluronidase system: (i) formation of catalytic complexes which leads to HA hydrolysis and (ii) formation of electrostatic hyaluronan hyaluronidase complexes in which hyaluronidase is catalytically inactive. As a consequence, the hyaluronidase activity can be strongly modulated by formation of electrostatic complexes involving either HA and/or hyaluronidase. The present report shows that this knowledge of the behavior of the hyaluronan/hyaluronidase system is important with respect to the detection, quantification, characterization, and use of hyaluronidase. It also strongly suggests that this behavior could be of importance under in vivo conditions, since, for example, it was shown that, according to its concentration, a hyaladherin (protein able to specifically bind HA) is able to either enhance or suppress the activity of a tumoral hyaluronidase.
