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

• Published in: Chinese chemical letters Vol. 23; no. 10; pp. 1193 - 1196
• Main Authors: Luo, Ying, Xu, Yu Xia, Bao, Qin Gui, Ding, Zhi Chun, Zhu, Cui Qing, Huang, Zhong Xian, Tan, Xiang Shi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2012; Department of Chemistry, Fudan University, Shanghai 200433, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China%State Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, China%Department of Chemistry, Fudan University, Shanghai 200433, China%Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China
• Subjects: Alzheimer's disease; Aβ1–42; ROS; Toxicity; Zn7MT3; 保护; 合作; 活性金属; 细胞毒作用; 羟基自由基; 金属硫蛋白; 铜毒性; 阿尔茨海默氏病; Zn7MT3; Toxicity; Aβ1–42; Alzheimer's disease; ROS; Aβ1-42
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2012.08.002

Cytotoxicity of Aft with redox active metals in neuronal cells has been implicated in the progression of Alzheimer＇s disease （AD）. Zn7MT-3 protects cell against AβCu2＋ toxicity. The roles of single domain proteins （α/β） and α-β domain-domain interaction of ZnTMT-3 in its anti-Aβ1-42-Cu2＋ toxicity activity were investigated herein. Aβ1-42 and four mutants of human MT3 （α/β domain, β（MT3）--α（MT1） and △31-34） were prepared and characterized. Aβ1-42-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.