2007年11月
Three histidine residues of amyloid-beta peptide control the redox activity of copper and iron
BIOCHEMISTRY
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- 巻
- 46
- 号
- 44
- 開始ページ
- 12737
- 終了ページ
- 12743
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/bi701079z
- 出版者・発行元
- AMER CHEMICAL SOC
Zinc, iron and copper are concentrated in senile plaques of Alzheimer disease. Copper and iron catalyze the Fenton-Haber-Weiss reaction, which likely contributes to oxidative stress in neuronal cells. In this study, we found that ascorbate oxidase activity and the intensity of ascorbate radicals measured using ESR spectroscopy, generated by free Cu(II), was decreased in the presence of amyloid-beta (A beta), the major component of senile plaques. Specifically, the ascorbate oxidase activity was strongly inhibited (85% decrease) in the presence of A beta 1-16 or A beta 1-42, whereas it was only slightly inhibited in the presence of A beta 1-12 or A beta 25-35 (< 20% inhibition). Ascorbate-dependent hydroxyl radical generation by free Cu(II) decreased in the presence of A beta in the identical order of A beta 1 -42, A beta 1-16 > A beta 1 - 12 and was abolished in the presence of 2-fold molar excess glycylhystidyllysine (GHK). Ascorbate oxidase activity and ascorbate-dependent hydroxyl radical generation by free Fe(III) were inhibited by A beta 1-42, A beta 1 - 16, and A beta 1 -12. Although Cu(II)-A beta shows a significant SOD-like activity, the rate constant for the reaction of superoxide with Cu(II)-A beta was much slower than that with SOD. Overall, our results suggest that His6, His13, and His14 residues of A beta 1-42 control the redox activity of transition metals present in senile plaques.
- リンク情報
- ID情報
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- DOI : 10.1021/bi701079z
- ISSN : 0006-2960
- PubMed ID : 17929832
- Web of Science ID : WOS:000250571800023