α-晶体蛋白对受铜离子氧化应激的醛糖还原酶的伴侣样活性。

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

作者信息

Moschini Roberta, Marini Isabella, Malerba Massimo, Cappiello Mario, Del Corso Antonella, Mura Umberto

机构信息

Department of Biology, Section of Biochemistry, University of Pisa, via S. Zeno, 51, 56126 Pisa, Italy.

出版信息

Arch Biochem Biophys. 2006 Sep 1;453(1):13-7. doi: 10.1016/j.abb.2006.03.008. Epub 2006 Mar 27.

DOI:10.1016/j.abb.2006.03.008

PMID:16615933

Abstract

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.

摘要

以牛晶状体醛糖还原酶（ALR2）作为蛋白质模型，研究了α-晶状体蛋白对铜诱导的蛋白质应激的保护作用。在化学计量比Cu2+/ALR2为2/1时，CuCl2诱导的ALR2氧化失活[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]，当金属离子浓度增加（Cu2+/ALR2>3）时，会伴随蛋白质聚集现象。蛋白质氧化先于蛋白质沉淀。α-晶状体蛋白以浓度依赖的方式阻止了ALR2的失活和沉淀。基于α-晶状体蛋白螯合铜的能力，给出了在低金属浓度下α-晶状体蛋白对ALR2的稳定作用的原理。然而，在较高铜浓度下α-晶状体蛋白发挥的整体保护作用，可能是由于α-晶状体蛋白易于与经历结构重排的靶蛋白相互作用的特殊特性所致。