Hydrogen peroxide can be generated by tau in the presence of Cu(II)
Section snippets
Materials and methods
Peptide synthesis. R2 peptide was synthesized on Fmoc-Wang resin by means of the standard Fmoc/tBu strategy and O-benzotriazol-N,N,N′,N′-tetramethyluronium hexafluorophosphate/1-hydroxybenzotriazol (HBTU/HOBt) protocol [21]. The peptide and all protecting groups were cleaved from the resin with TFA containing phenol (5%), thioanisole (5%), ethanedithiol (2.5%), and water (5%) for 120 min [22]. The crude peptide was purified by reverse phase HPLC using an ODS-UG-5 column (Develosil) with a linear
R2 is capable of reducing copper
We first analyzed the copper reduction capacity of R2 peptide. R2 peptide, ascorbic acid (as a positive control) and BSA (as a negative control) were co-incubated with copper ions at 37 °C for 30 min. Cu(I) formation was monitored by using BC, which formed a complex with Cu(I), showing an absorbance at 480 nm. Results indicate that R2 peptide showed copper reduction capacity, though weaker than ascorbic acid, a strong reducing agent (Fig. 1). In the same experiments, BSA showed hardly any copper
Discussion
Our work clearly demonstrated that copper can be reduced by tau peptide and can catalyze tau peptide oxidation. However, iron, another redox-active metal ion, is incapable of catalyzing tau oxidation. This is different from Aβ peptide, which can reduce both copper and iron and may generate hydrogen peroxide in the presence of either of them [7], [10]. This could be attributed to the different affinity of tau with these two metals. It has been reported that copper may bind tightly with tau
Acknowledgments
The authors appreciate the financial support from the National Natural Science Foundation of China (Nos. 20532020 and 20672067), and the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, IRT0404).
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