NR ALQI
AU Thackray,A.M.; Knight,R.; Haswell,S.J.; Bujdoso,R.; Brown,D.R.
TI Metal imbalance and compromised antioxidant function are early changes in prion disease
QU Biochemical Journal 2002 Feb 15; 362(1): 253-8
PT journal article
AB The prion protein (PrP) has been shown to bind copper. In the present study we have investigated whether prion disease in a mouse scrapie model resulted in modification of metal concentrations. We found changes in the levels of copper and manganese in the brains of scrapie-infected mice prior to the onset of clinical symptoms. Interestingly, we noted a major increase in blood manganese in the early stages of disease. Analysis of purified PrP from the brains of scrapie-infected mice also showed a reduction in copper binding to the protein and a proportional decrease in antioxidant activity between 30 and 60 days post-inoculation. We postulate that alterations in trace-element metabolism as a result of changes in metal binding to PrP are central to the pathological modifications in prion disease.
MH Animal; Antioxidants/*metabolism; Blotting, Western; Brain/enzymology/metabolism; Copper/*metabolism; Endopeptidase K/metabolism; Female; Male; Manganese/*metabolism; Mice; Mice, Inbred C57BL; Prion Diseases/*metabolism; Prions/isolation & purification/metabolism; Superoxide Dismutase/metabolism; Support, Non-U.S. Gov't
AD Alana M. Thackray, Raymond Bujdoso, Centre for Veterinary Science, Madingley Road, University of Cambridge, Cambridge CB3 0ES, U.K.; Robert Knight, Stephen J. Haswell, Department of Chemistry, University of Hull, Hull HU6 7RX, U.K.; David R. Brown (bssdrb@bath.ac.uk), Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
SP englisch
PO England