2341 Ageing and the chaperone properties of α-crystallin

w This work aims to test the hypothesis that age-related loss of the molecular chaperone activity of a-crystallin may be involved in the precipitation of lens proteins and subsequent cataract development. &&Q& acrystallins of dierent ages were isolated from concentric tissue layers removed from foetal and adull bovine lenses. They were examined for chaperone activity by measuring their ability to inhibit the thermal denaturation and precipitation of p-crystallin. They were also examined for the changes in their molecular weights (light scattering) and polypeptide properties (PAGE) which are usually attributed to Ffeing. Protein synthesis was examined by measuring incorporated C-Leu in concentric tissue layers after incubation of the whole lens. f&& The chaperone activity decreases rapidly from the epithelium towards the centre of the lens. Almost all activity is gone before fibre cells have matured and lost their capacity for protein synthesis. This occurs in both foetal and adult lenses. The loss of activity and the protein synthesis pattern closely resemble the distribution patterns that have been observed previously for glutathione reductase and hexokinase activities. No obvious correlation was found wtih agerelated modifications such as the molecular weight increases or polypeptide modification. Q&i&@ The decrease in a-crystallin chaperone activity appears to be associated with maturation of fibre cells and not with ageing of the lens. The data suggest that chaperone activity is only required in the epithelium and/or newly differentiated fibre cells. What its function may be cannot be ascertained. However, it is clear that loss of the activity is unrelated to the extensive precipitation of proteins which takes place in the age-related nuclear cataract.