Prion-derived copper-binding peptide fragments catalyze the generation of superoxide anion in the presence of aromatic monoamines.
Prion-derived copper-binding peptide fragments catalyze the generation of superoxide anion in the presence of aromatic monoamines.
复制标题
DOI：
10.7150/ijbs.3.57
复制
发表时间：
2006-11-09
影响因子：
9.2
通讯作者：
Kawano T
中科院分区：
文献类型：
--
作者：
Kawano T
目的：研究已经提出铜结合形式的朊蛋白（PrP）作为支持神经元功能的抗氧化剂和作为导致涉及活性氧物质产生的神经退行性过程的促氧化剂的两种相反的作用。本研究的目的是测试的假设，其中假定的铜结合肽来自PrP功能作为可能的催化剂的单胺依赖性转化过氧化氢超氧化物在体外。材料与方法：四个肽对应的铜（II）结合图案在PrP的合成和用于分析的肽催化生成的超氧化物的存在下，铜（II）和其他因素自然存在于神经元组织。结果如下：在测试的铜结合肽中，对应于在螺旋区域中的铜结合位点的氨基酸序列被证明是最活跃的超氧化物生成在铜（II），过氧化氢和芳香族单胺，已知的前体或中间体的神经递质的存在下。在测试的单胺中，三种化合物，即苯乙胺，酪胺和苄胺被证明是由铜结合的螺旋肽产生超氧化物反应的良好底物。结论：这些反应可能在朊病毒病的发展中发挥作用。
Objectives: Studies have proposed two opposing roles for copper-bound forms of prion protein (PrP) as an anti-oxidant supporting the neuronal functions and as a pro-oxidant leading to neurodegenerative process involving the generation of reactive oxygen species. The aim of this study is to test the hypothesis in which putative copper-binding peptides derived from PrP function as possible catalysts for monoamine-dependent conversion of hydrogen peroxide to superoxide in vitro. Materials and methods: Four peptides corresponding to the copper (II)-binding motifs in PrP were synthesized and used for analysis of peptide-catalyzed generation of superoxide in the presence of Cu (II) and other factors naturally present in the neuronal tissues. Results: Among the Cu-binding peptides tested, the amino acid sequence corresponding to the Cu-binding site in the helical region was shown to be the most active for superoxide generation in the presence of Cu(II), hydrogen peroxide and aromatic monoamines, known precursors or intermediates of neurotransmitters. Among monoamines tested, three compounds namely phenylethylamine, tyramine and benzylamine were shown to be good substrates for superoxide-generating reactions by the Cu-bound helical peptide. Conclusions: Possible roles for these reactions in development of prion disease were suggested.