Cu(II) potentiation of Alzheimer Abeta1-40 cytotoxicity and transition on its secondary structure.
Mounting evidence has shown that dyshomeostasis of the redox-active biometals such as Cu and Fe can lead to oxidative stress, which plays a key role in the neuropathology of Alzheimer' disease (AD). Here we demonstrate that with the formation of Cu(II).beta1-40 complexes, copper markedly potentiates the neurotoxicity exhibited by beta-amyloid peptide (Ab). A greater amount of hydrogen peroxide was released when Cu(II).beta1-40 complexes was added to the xanthine oxidase/xanthine system detected by potassium iodide spectrophotometry. Copper bound to Abeta1-40 was observed by electron paramagnetic resonance (EPR) spectroscopy. Circular dichroism (CD) studies indicated that copper chelation could cause a structural transition of Abeta. The addition of copper to Ab introduced an increase on beta-sheet as well as alpha-helix, which may be responsible for the aggregation of Abeta. We hypothesized that Abeta aggregation induced by copper may be responsible for local injury in AD. The interaction between Cu(2+) and Ab also provides a possible mechanism for the enrichment of metal ions in amyloid plaques in the AD brain.
Dai
Xue-Ling
XL
College of Life Science, Capital Normal University, Beijing 100037, China.
Sun
Ya-Xuan
YX
Jiang
Zhao-Feng
ZF
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002413:Cations, Divalent; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D004578:Electron Spin Resonance Spectroscopy; D006861:Hydrogen Peroxide / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011193:Potassium Iodide / Q000737:chemistry; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry; D019820:Xanthine / Q000737:chemistry; D014969:Xanthine Oxidase / Q000737:chemistry
D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D019820:Xanthine; D011193:Potassium Iodide; D003300:Copper; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase