Time-dependent DNA condensation induced by amyloid beta-peptide.
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.
Yu
Haijia
H
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.
Ren
Jinsong
J
Qu
Xiaogang
X
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008670:Metals / Q000737:chemistry; D009474:Neurons / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D015032:Zinc / Q000737:chemistry
D016229:Amyloid beta-Peptides; D007477:Ions; D008670:Metals; D010455:Peptides; D003300:Copper; D004247:DNA; D015032:Zinc