Degradation of cartilage proteoglycans by elastase is dependent on charge-mediated interactions.
We investigated the mechanism of cartilage degradation by pancreatic elastase as a model system for the action of cationic proteases such as leukocyte elastase and cathepsin-G. It is shown that the cationic properties of elastase contribute to its proteolytic potential with respect to cartilage degradation. Elastase preparations with neutral or negative charge, obtained by chemical modification were far less effective in cartilage degradation than the cationic, native enzyme. Modification of elastase did not affect the active site of the enzyme as shown by kinetic studies, nor did it alter the complexing with alpha-1-proteinase inhibitor. Quantitative and autoradiographic studies indicate that the positive charge of the enzyme favors the penetration in cartilage and interaction with the polyanionic proteoglycan substrate. It is concluded that the potent cartilage-degrading activity of elastase is dependent on charge-mediated interactions with its substrate.
Schalkwijk
J
J
Department of Rheumatology, St. Radboud Hospital, Nijmegen, The Netherlands.
Joosten
L A
LA
van den Berg
W B
WB
van de Putte
L B
LB
D002358:Cartilage, Articular / Q000378:metabolism*; D002412:Cations; D002850:Chromatography, Gel; D007525:Isoelectric Focusing; D007700:Kinetics; D010196:Pancreatic Elastase / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D013387:Succinic Anhydrides / Q000378:metabolism
D002412:Cations; D011509:Proteoglycans; D013387:Succinic Anhydrides; D010196:Pancreatic Elastase