NR APHY
AU Hijazi,N.; Shaked,Y.; Rosenmann,H.; Ben-Hur,T.; Gabizon,R.
TI Copper binding to PrPc may inhibit prion disease propagation
QU Brain Research 2003 Dec 12; 993(1-2): 192-200
PT journal article
AB Although it has been well established that PrPc, the normal isoform of PrPsc, is a copper-binding protein, the role of this metal in the function of PrPc as well as in prion disease pathology remains unclear. Here, we show that when scrapie-infected neuroblastoma cells were cultured in the presence of copper, the accumulation of PrPsc in these cells was markedly reduced. In addition, our results indicate that when normal neuroblastoma cells were cultured in the presence of copper ions, they could no longer bind and internalize PrPsc. In another set of experiments, copper was added to the drinking water of normal and scrapie-infected hamsters. Our results show that administration of copper to normal hamsters induced cerebellar PrPc accumulation. Most important, a significant delay in prion disease onset was observed when scrapie-infected hamsters were treated with copper. As shown before for neuroblastoma cells, also in vivo most of the copper-induced accumulation of PrPc was intracellular. We hypothesized that PrPc internalization by copper may hinder PrPsc interaction with this molecule, and thereby affect prion disease propagation.
IN Durch Kupfer im Medium wurde bei Neuroblastomzellen die PrPsc-Akkubulation deutlich reduziert und Kupfer im Trinkwasser förderte in den Gehirnen normaler Hamster die PrPc-Akkumulation innerhalb der Zellen, während es bei Scrapie-infizierten Hamstern die Inkubationszeit deutlich verlängert.
MH Animals; Brain/drug effects/metabolism/pathology; Cell Line; Comparative Study; Copper Sulfate/administration & dosage/*therapeutic use; Dose-Response Relationship, Drug; Hamsters; Human; Immunoblotting/methods; Immunohistochemistry/methods; Infection; Male; Microscopy, Confocal/methods; PrPc Proteins/*metabolism; PrPsc Proteins/drug effects/genetics/*metabolism; Prion Diseases/*prevention & control; Protein Binding/drug effects; Protein Transport/drug effects; Purkinje Cells/pathology; RNA, Messenger/biosynthesis; Reverse Transcriptase Polymerase Chain Reaction/methods; Spectrophotometry, Atomic/methods; Time Factors
AD Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Ein Karem, Jerusalem 91120, Israel.
SP englisch
PO Niederlande