期刊
METALLOMICS
卷 5, 期 7, 页码 861-870出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3mt20282h
关键词
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资金
- National Natural Science Foundation of China [31070731, 21271131, 30901182]
- Natural Science Foundation of Guangdong Province [10151806001000023]
- Grants of Shenzhen Municipal Science and Technology Industry and Information Technology Commission Research [CXB201005240008A]
Aggregation and cytotoxicity of the amyloid-beta (A beta) peptide with transition metal ions in neuronal cells have been suggested to be involved in the progression of Alzheimer's disease (AD). A therapeutic strategy to combat this incurable disease is to design chemical agents to target metal-A beta species. Selenoproteins are a group of special proteins that contain the 21st amino acid Sec in their sequence. Due to the presence of Sec, studies of this group of proteins are basically focused on their roles in regulating redox potential and scavenging reactive oxygen species. Here, we reported that the His-rich domain of selenoprotein P (SelP-H) and the Sec-to-Cys mutant selenoprotein M (SelM') are capable of binding transition metal ions and modulating the Zn2+-mediated A beta aggregation, ROS production and neurotoxicity. SelM' (U48C) and SelP-H were found to coordinate 0.5 and 2 molar equivalents of Zn2+/Cd2+ with micromolar and submicromolar affinities, respectively. Metal binding induced the structural changes in SelP-H and SelM' according to the circular dichorism spectra. Zn2+ binding to A beta(42) almost completely suppressed A beta(42) fibrillization, which could be significantly restored by SelP-H and SelM', as observed by thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM). Interestingly, both SelP-H and SelM' inhibited Zn2+-A beta(42)-induced neurotoxicity and the intracellular ROS production in living cells. These studies suggest that SelP and SelM may play certain roles in regulating redox balance as well as metal homeostasis.
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