β-淀粉样肽诱导的时间依赖性DNA凝聚
Time-dependent DNA condensation induced by amyloid beta-peptide.
作者信息
Yu Haijia, Ren Jinsong, Qu Xiaogang
机构信息
Division of Biological Inorganic Chemistry, Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Changchun, Jilin, China.
出版信息
Biophys J. 2007 Jan 1;92(1):185-91. doi: 10.1529/biophysj.106.093559. Epub 2006 Oct 6.
Abstract
The major protein component of the amyloid deposition in Alzheimer's disease is a 39-43 residue peptide, amyloid beta (Abeta). Abeta is toxic to neurons, although the mechanism of neurodegeneration is uncertain. Evidence exists for non-B DNA conformation in the hippocampus of Alzheimer's disease brains, and Abeta was reportedly able to transform DNA conformation in vitro. In this study, we found that DNA conformation was altered in the presence of Abeta, and Abeta induced DNA condensation in a time-dependent manner. Furthermore, Abeta sheets, serving as condensation nuclei, were crucial for DNA condensation, and Cu(2+) and Zn(2+) ions inhibited Abeta sheet-induced DNA condensation. Our results suggest DNA condensation as a mechanism of Abeta toxicity.
摘要
阿尔茨海默病中淀粉样沉积的主要蛋白质成分是一种由39 - 43个氨基酸残基组成的肽，即β淀粉样蛋白（Aβ）。尽管神经退行性变的机制尚不清楚，但Aβ对神经元有毒性。有证据表明，在阿尔茨海默病患者大脑的海马体中存在非B型DNA构象，且据报道Aβ能够在体外改变DNA构象。在本研究中，我们发现Aβ存在时DNA构象会发生改变，并且Aβ能以时间依赖的方式诱导DNA凝聚。此外，作为凝聚核的Aβ片层对于DNA凝聚至关重要，而铜离子（Cu²⁺）和锌离子（Zn²⁺）会抑制Aβ片层诱导的DNA凝聚。我们的结果表明，DNA凝聚是Aβ毒性作用的一种机制。
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本文引用的文献
1
Cu Inhibits the Aggregation of Amyloid β-Peptide(1-42) in vitro.铜在体外抑制β-淀粉样肽（1-42）的聚集。
Angew Chem Int Ed Engl. 2001 Jun 18;40(12):2274-2277. doi: 10.1002/1521-3773(20010618)40:12<2274::AID-ANIE2274>3.0.CO;2-5.
2
Carbon nanotubes selective destabilization of duplex and triplex DNA and inducing B-A transition in solution.碳纳米管对双链和三链DNA的选择性去稳定作用以及在溶液中诱导B - A转变。
Nucleic Acids Res. 2006 Aug 2;34(13):3670-6. doi: 10.1093/nar/gkl513. Print 2006.
3
PolydA and polyrA self-structured by a europium and amino acid complex.由铕和氨基酸络合物自组装而成的聚dA和聚rA。
FEBS Lett. 2006 Jun 26;580(15):3726-30. doi: 10.1016/j.febslet.2006.05.046. Epub 2006 May 30.
4
Reversible B/Z-DNA transition under the low salt condition and non-B-form polydApolydT selectivity by a cubane-like europium-L-aspartic acid complex.在低盐条件下，类立方烷铕-L-天冬氨酸配合物实现可逆的B型/Z型DNA转变以及对非B型聚dA聚dT的选择性。
Biophys J. 2006 May 1;90(9):3203-7. doi: 10.1529/biophysj.105.078402. Epub 2006 Feb 10.
5
Monomolecular DNA nanoparticles for intravenous delivery of genes.用于基因静脉内递送的单分子DNA纳米颗粒。
J Am Chem Soc. 2005 Aug 17;127(32):11436-41. doi: 10.1021/ja0522332.
6
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Nat Cell Biol. 2004 Nov;6(11):1054-61. doi: 10.1038/ncb1104-1054.
7
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Free Radic Biol Med. 2004 Jan 15;36(2):180-8. doi: 10.1016/j.freeradbiomed.2003.10.018.
8
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J Mol Neurosci. 2004;22(1-2):19-31. doi: 10.1385/jmn:22:1-2:19.
9
Polyamine-dependent gene expression.多胺依赖性基因表达
Cell Mol Life Sci. 2003 Jul;60(7):1394-406. doi: 10.1007/s00018-003-2332-4.
10
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