Copper (II) promotes the formation of soluble neurotoxic PrP oligomers in acidic environment.

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 Cu(2+) plays a vital role in the formation of soluble PrP oligomers. A Cu(2+)-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, Cu(2+) promotes the formation of neurotoxic soluble PrP oligomers.

• Authors: Di Wu, Wentao Zhang, Qingying Luo, Kan Luo, Liqin Huang, Wenxi Wang, Tao Huang, Rui Chen, Yi Lin, Daiwen Pang, Gengfu Xiao
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 111 Issue 3 Pg. 627-33 (Oct 15 2010) ISSN: 1097-4644 [Electronic] United States
• PMID: 20564047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 Wiley-Liss, Inc.

Chemical References

• Acids
• Prions
• Copper

Topics

• Acids
• Apoptosis
• Cell Line, Tumor
• Copper (pharmacology)
• Humans
• Hydrogen-Ion Concentration
• Neuroblastoma (pathology)
• Prions (biosynthesis, chemistry, toxicity)
• Protein Conformation
• Protein Multimerization (drug effects)
• Solubility