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  • Title: A comprehensive study on the generation of reactive oxygen species in Cu-Aβ-catalyzed redox processes.
    Author: Huang H, Lou X, Hu B, Zhou Z, Chen J, Tian Y.
    Journal: Free Radic Biol Med; 2019 May 01; 135():125-131. PubMed ID: 30849487.
    Abstract:
    In the amyloid plaques, a signature of AD, abnormally high Cu2+ concentrations are found bound to Aβ. Most of previous studies reported that Cu-Aβ could contribute to oxidative stress, as H2O2 and •OH are catalytically generated by Cu-Aβ with the assistance of biological reductant, with only one recent report stated that free O2•- is also generated in the Cu-Aβ catalyzed processes, where an indirect technique was applied. To comprehensively investigate the free radicals produced during this Cu-Aβ-mediated process with a biological reductant, DNA-cleavage assay, an indirect method, and two direct methods including electron paramagnetic resonance (EPR) spectroscopy and transient absorption spectroscopy (TAS), both having qualitative and quantitative power, were employed in this work. All the experimental results obtained from the three methods demonstrated that Cu-Aβ in the biological reducing environment was not only able to catalyze the production of H2O2 and •OH, but also to generate free O2•-. The results further indicated that O2•- was the precursor of H2O2 and •OH. It is also important to note that the results obtained from EPR spectroscopy and TAS provided direct evidence for the presence of O2•- and •OH. By virtue of the direct techniques, we also found that the longest peptide fragments of Aβ16, Aβ40, and Aβ42 produced the least radicals with a lowest rate. More interestingly, the fibrillar forms of Aβ generated less O2•- and •OH compared with oligomeric and monomeric forms.
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