Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, People's Republic of China.
Metallomics. 2020 Nov 1;12(11):1802-1810. doi: 10.1039/d0mt00143k. Epub 2020 Oct 21.
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-Cu 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 Cu on the aggregation of NKB was studied. As evidenced by cyclic voltammetry, the redox potential of NKB-Cu 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 Cu-mediated reactive oxygen species (ROS) production in the presence of ascorbic acid (AA). In comparison with equivalent Cu, the peptide-Cu 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/Cu interactions and the toxicity mechanism of Cu associated with neurodegenerative diseases.
神经激肽 B（NKB）的速激肽神经肽是一种铜结合淀粉样肽，在中枢和外周神经系统的生理功能和病理生理过程的调节中具有重要作用。在这项工作中，通过质谱证实了 NKB-Cu 复合物以 1:1 的化学计量比形成。通过噻唑蓝 T（ThT）荧光测定法和原子力显微镜（AFM）研究了 NKB 及其突变体的自组装，同时研究了 Cu 对 NKB 聚集的影响。循环伏安法的结果表明，NKB-Cu 的氧化还原电位为 0.77 V（相对于 Ag/AgCl）。已经证明，在存在抗坏血酸（AA）的情况下，低浓度的 NKB 通过抑制 Cu 介导的活性氧（ROS）产生来发挥其神经保护功能。与等量的 Cu 相比，在没有 AA 的情况下，肽-Cu 聚集体使 PC-12 细胞的活力受到更严重的损害。这些结果对于理解 NKB/Cu 相互作用以及与神经退行性疾病相关的 Cu 的毒性机制应该具有非常重要的价值。
