The α and β domains of human metallothionein-3 co-operatively protect against Aβ1-42-Cu2+ cytotoxicity

Cytotoxicity of A beta with redox active metals in neuronal cells has been implicated in the progression of Alzheimer's disease (AD). Zn7MT-3 protects cell against A beta-Cu2+ toxicity. The roles of single domain proteins (alpha/beta) and a P domain domain interaction of Zn7MT-3 in its anti-A beta(1-42)-Cu2+ toxicity activity were investigated herein. A beta(1-42) and four mutants of human MT3 (alpha/beta domain, beta (MT3)-alpha (MT1) and Delta 31-34) were prepared and characterized. A beta(1-42)-Cu2+ induced hydroxyl radical and ROS production with/without Zn-MTs were measured by fluorescence spectroscopy and DCFH-DA in living cells, respectively. These results indicate that the two domains form a co-operative unit and each of them is indispensable in conducting its bioactivity. (C) 2012 Xiang Shi Tan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.