Chaperone-like activity of alpha-crystallin toward aldose reductase oxidatively stressed by copper ion.
The protective action of alpha-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 alpha-crystallin in a concentration-dependent manner. The rationale for the stabilization of ALR2 exerted by alpha-crystallin at low metal concentration is given on the basis of the ability of alpha-crystallin to chelate copper. However, the overall protective action exerted by alpha-crystallin at higher copper concentration may be explained invoking the contribution of the special features of alpha-crystallin to easily interact with target proteins undergoing structural rearrangement.
Moschini
Roberta
R
Department of Biology, Section of Biochemistry, University of Pisa, via S. Zeno, 51, 56126 Pisa, Italy.
Marini
Isabella
I
Malerba
Massimo
M
Cappiello
Mario
M
Del Corso
Antonella
A
Mura
Umberto
U
D000449:Aldehyde Reductase / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007477:Ions; D007908:Lens, Crystalline / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D038201:alpha-Crystallins / Q000737:chemistry*
D007477:Ions; D018832:Molecular Chaperones; D038201:alpha-Crystallins; D003300:Copper; D000449:Aldehyde Reductase; D010100:Oxygen