Free radical generation of protease-resistant prion after substitution of manganese for copper in bovine brain homogenate.
The exchange between copper and seven transition metals is studied in a bovine brain obex homogenate according to the redox status of the medium. In reductive conditions, almost all the studied metals can substitute for copper when it is in the reduced form Cu+. This substitution is reversible, since copper uptake as Cu++ is restored in an oxidizing medium but only Co++, Ni++ and Mn++, in this decreasing order, can substitute perfectly for copper in bovine brain homogenate. To study free radical effects on bovine brain proteins, at first a copper substitution was processed in order to inhibit superoxide dismutase-like protective properties against free radicals in copper metalloproteins. Manganese was selected since a brain copper decrease correlated with a manganese increase is well-known in transmissible spongiform encephalopathies. Results for bovine brain homogenate, initially negative in the Western blot Prionics test, indicate that the substitution of manganese for copper in a reducing medium and exposure to UVA-induced free radicals produce proteinase K resistant prion. These findings suggest that an impairment in brain metal homeostasis leading to oxidative abnormalities may be involved in transmissible spongiform encephalopathies.
Deloncle
Roger
R
Université François Rabelais de Tours, Bio-Inorganic Chemistry Laboratory, Faculty of Pharmacy, 31 Avenue Monge, 37200 Tours, France. deloncle@univ-tours.fr
Guillard
Olivier
O
Bind
Jean Louis
JL
Delaval
José
J
Fleury
Nadia
N
Mauco
Gérard
G
Lesage
Gérard
G
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D003300:Copper / Q000494:pharmacology*; D003956:Dialysis / Q000379:methods; D005609:Free Radicals / Q000378:metabolism*; D046911:Macromolecular Substances / Q000737:chemistry; D008345:Manganese / Q000494:pharmacology*; D019216:Metals, Heavy; D010084:Oxidation-Reduction / Q000187:drug effects; D010447:Peptide Hydrolases / Q000378:metabolism; D011328:Prions / Q000737:chemistry*; D014466:Ultraviolet Rays / Q000009:adverse effects
D005609:Free Radicals; D046911:Macromolecular Substances; D019216:Metals, Heavy; D011328:Prions; D008345:Manganese; D003300:Copper; D010447:Peptide Hydrolases