Yu Haijia, Ren Jinsong, Qu Xiaogang
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.
Biophys J. 2007 Jan 1;92(1):185-91. doi: 10.1529/biophysj.106.093559. Epub 2006 Oct 6.
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.
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。
