Age-related changes in proteolysis of aberrant crystallin in bovine lens cell-free preparations

Bovine alpha-crystallin fragments were prepared by H2O2/Cu2(+)-mediated free-radical treatment (which generated 15.1 and 16.6 K Mr fragments) and cyanogen bromide cleavage (which generated 8.4, 13.8 and 16.8 K Mr fragments). Proteolysis of the fragments and native and denatured alpha-crystallin was then compared using bovine lens homogenates prepared from either cortex or cores of lenses obtained from animals of different ages (foetal, 1.5 years and 6.5 years old). In all preparations the fragments were more rapidly degraded than the denatured but uncleaved protein, while the untreated crystallin was only slightly susceptible to proteolytic attack. Both developmental and age-related differences in proteolytic activity towards the aberrant crystallins were detected, most notably a marked age-related decline in the fragment catabolism in preparations obtained from the cores. Should a similar decline occur in human lenses then the changes which we have detected may be important contributary factors towards cataractogenesis.