Copper (II) promotes the formation of soluble neurotoxic PrP oligomers in acidic environment |
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Authors: | Di Wu Wentao Zhang Qingying Luo Kan Luo Liqin Huang Wenxi Wang Tao Huang Rui Chen Yi Lin Daiwen Pang Gengfu Xiao |
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Affiliation: | 1. State Key Laboratory of Virology and Modern Virology Research Centre, College of Life Sciences, Wuhan University, Wuhan 430072, PR China;2. College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, PR China;3. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China |
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Abstract: | Prion diseases are classically considered to be “amyloid diseases” caused by the deposition of amyloid fibrils in the brain. Recent studies identified soluble oligomers of PrP (prion protein) in damaged neuronal tissue. However, the details of PrP oligomerization are still unclear. In this study, we demonstrate that Cu2+ plays a vital role in the formation of soluble PrP oligomers. A Cu2+‐triggered structural conversion of PrP (90–231) to a β‐sheet isoform in pH 5.0 buffer was revealed by circular dichroism spectra and fluorescence measurement. Soluble oligomers were isolated by size exclusion chromatography from experimental solutions, allowing atomic force microscopy to reveal their morphology. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and flow cytometry assays demonstrated that oligomeric PrP induced significant damage in and apoptosis of neuroblastoma SK‐N‐SH cells. These results indicate that in an acidic environment, Cu2+ promotes the formation of neurotoxic soluble PrP oligomers. J. Cell. Biochem. 111: 627–633, 2010. © 2010 Wiley‐Liss, Inc. |
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Keywords: | prion oligomer copper acidic pH toxicity |
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