superoxide radicals have potent degradative actions on whole cartilage in vitro. Cleavage of peptide bonds in the polypeptide of proteoglycan

Bovine nasal carti lage slices, biosynthetically labelled in their proteoglycan with SSSO~, were used as substrate for the a t tack of free radicals generated on exposure to a Co 6~ source (which allows study of single radical s p e c i e s ) , and by c h e m i c a l and e n z y m a t i c means. S y s t e m s g e n e r a t i n g hydroxyl ( O H ' ) and superoxide (02") radicals degraded the proteoglycan efficiently, w h i l e t he h y d r o p e r o x y rad ica l ( H O I " ) was less e f f i c i e n t ; add i t ion of appropriate radical scavengers inhibited degradation. The radioactive products were heterogeneous in molecular size, but with doses up to 3600 Gy were the same size range as intact chondroitin sulphate. They contained free amino groups, and more were liberated by aminopeptidase M digestion~ implying that at least a small peptide was present. Thus a major site of radical a t tack may be the polypeptide chain. We suggest that free-radical fragmentation of p o l y p e p t i d e s may be important both in extracellular catabolism and in intracellular proteolysis.