1. A copper complex formed with neurokinin B: binding stoichiometry, redox properties, self-assembly and cytotoxicity
- Author
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Ping Yang, Miao Chen, Yaliang Huang, Jianxiu Wang, Ning Xia, and Lin Liu
- Subjects
inorganic chemicals ,Time Factors ,Amyloid ,Cell Survival ,Neurokinin B ,Biophysics ,Peptide ,Biochemistry ,Redox ,PC12 Cells ,Mass Spectrometry ,Biomaterials ,chemistry.chemical_compound ,Electrochemistry ,Animals ,Benzothiazoles ,Cytotoxicity ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Death ,Metals and Alloys ,Ascorbic acid ,Rats ,chemistry ,Chemistry (miscellaneous) ,Thioflavin ,Oxidation-Reduction ,Copper ,Protein Binding - Abstract
The tachykinin neuropeptide of neurokinin B (NKB) is a copper-binding amyloid peptide with important roles in the regulation of physiological functions and pathophysiological processes in the central and peripheral nervous systems. In this work, the formation of a NKB–Cu2+ complex in a 1 : 1 stoichiometry was confirmed by mass spectrometry. The self-assembly of NKB and its mutant species was investigated by Thioflavin T (ThT) fluorescence assay and atomic force microscopy (AFM), and at the same time, the effect of Cu2+ on the aggregation of NKB was studied. As evidenced by cyclic voltammetry, the redox potential of NKB–Cu2+ was determined to be 0.77 V (vs. Ag/AgCl). It has been demonstrated that NKB at low concentrations exerts its neuroprotective function by inhibiting Cu2+-mediated reactive oxygen species (ROS) production in the presence of ascorbic acid (AA). In comparison with equivalent Cu2+, the peptide–Cu2+ aggregates aggravated the viability of PC-12 cells more seriously in the absence of AA. These results should be extremely valuable for understanding the NKB/Cu2+ interactions and the toxicity mechanism of Cu2+ associated with neurodegenerative diseases.
- Published
- 2020