Document Detail

Age-related changes in aggrecan glycosylation affect cleavage by aggrecanase.
MedLine Citation:
PMID:  10991945     Owner:  NLM     Status:  MEDLINE    
Aggrecan degradation involves proteolytic cleavage of the core protein within the interglobular domain. Because aggrecan is highly glycosylated with chondroitin sulfate (CS) and keratan sulfate (KS), we investigated whether glycosylation affects digestion by aggrecanase at the Glu(373)-Ala(374) bond. Treatment of bovine aggrecan monomers to remove CS and KS resulted in loss of cleavage at this site, suggesting that glycosaminoglycans (GAGs) play a role in cleavage at the Glu(373)-Ala(374) bond. In contrast, MMP-3 cleavage at the Ser(341)-Phe(342) bond was not affected by glycosidase treatment of aggrecan. Removal of KS, but not CS, prevented cleavage at the Glu(373)-Ala(374) bond. Thus, KS residues may be important for recognition of this cleavage site by aggrecanase. KS glycosylation has been observed at sites adjacent to the Glu(373)-Ala(374) bond in steer aggrecan, but not in calf aggrecan (Barry, F. P., Rosenberg, L. C., Gaw, J. U., Gaw, J. U., Koob, T. J., and Neame, P. J. (1995) J. Biol. Chem. 270, 20516-20524). Interestingly, although we found that aggrecanase degraded both calf and steer cartilage aggrecan, the proportion of fragments generated by cleavage at the Glu(373)-Ala(374) bond was higher in steer than in calf, consistent with our observations using aggrecan treated to remove KS. We conclude that the GAG content of aggrecan influences the specificity of aggrecanase for cleavage at the Glu(373)-Ala(374) bond and suggest that age may be a factor in aggrecanase degradation of cartilage.
M A Pratta; M D Tortorella; E C Arner
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-02-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  39096-102     Citation Subset:  IM    
Inflammatory Diseases Research, The DuPont Pharmaceutical Company, Experimental Station Wilmington, Delaware 19880-0400, USA.
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MeSH Terms
Age Factors
Alanine / chemistry
Blotting, Western
Chondroitin Sulfates / metabolism
Chondroitinases and Chondroitin Lyases / pharmacology
Endopeptidases / metabolism*
Extracellular Matrix Proteins*
Glutamine / chemistry
Glycosaminoglycans / metabolism
Glycoside Hydrolases*
Keratan Sulfate / metabolism
Lectins, C-Type
Matrix Metalloproteinase 3 / metabolism
Phenylalanine / chemistry
Proteoglycans / metabolism*
Serine / chemistry
Time Factors
beta-Galactosidase / pharmacology
Reg. No./Substance:
0/Aggrecans; 0/Extracellular Matrix Proteins; 0/Glycosaminoglycans; 0/Lectins, C-Type; 0/Proteoglycans; 56-41-7/Alanine; 56-45-1/Serine; 56-85-9/Glutamine; 63-91-2/Phenylalanine; 9007-28-7/Chondroitin Sulfates; 9056-36-4/Keratan Sulfate; EC 3.2.1.-/Glycoside Hydrolases; EC endo-1,4-beta-galactosidase; EC; EC 3.4.-/Endopeptidases; EC Metalloproteinase 3; EC 3.4.99.-/aggrecanase; EC 4.2.2.-/Chondroitinases and Chondroitin Lyases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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