Chaperone-like activity of α-crystallin toward aldose reductase oxidatively stressed by copper ion

The protective action of α-crystallin against copper-induced protein stress is studied using bovine lens aldose reductase (ALR2) as protein model. The oxidative inactivation of ALR2 induced by CuCl2 at the stoichiometric Cu2+/ALR2 ratio of 2/1 [I. Cecconi, M. Moroni, P.G. Vilardo, M. Dal Monte, P. Borella, G. Rastelli, L. Costantino, D. Garland, D. Carper, J.M. Petrash, A. Del Corso, U. Mura, Biochemistry 37 (1998) 14167–14174] is accompanied by protein aggregation phenomena when the metal ion concentration is increased (Cu2+/ALR2 > 3). Protein oxidation precedes protein precipitation. Both inactivation and precipitation of ALR2 are prevented by α-crystallin in a concentration-dependent manner. The rationale for the stabilization of ALR2 exerted by α-crystallin at low metal concentration is given on the basis of the ability of α-crystallin to chelate copper. However, the overall protective action exerted by α-crystallin at higher copper concentration may be explained invoking the contribution of the special features of α-crystallin to easily interact with target proteins undergoing structural rearrangement.