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Copper (II) ions potently inhibit purified PrPres amplification
Author(s) -
Orem Nicholas R.,
Geoghegan James C.,
Deleault Nathan R.,
Kascsak Richard,
Supattapone Surachai
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03650.x
Subject(s) - in vitro , in vivo , chemistry , pathogenesis , scrapie , hamster , gene isoform , microbiology and biotechnology , chelation , molecule , peptide , biochemistry , biology , prion protein , inorganic chemistry , immunology , medicine , disease , organic chemistry , pathology , gene
The structural conversion of a host protein, PrP C , into a protease‐resistant isoform, PrPres, is the central event in the pathogenesis of infectious prion diseases. Purification of native PrP C molecules from hamster brain by either cation exchange or immobilized chelator chromatographic resins yielded preparations that supported efficient amplification of scrapie‐induced PrPres in vitro . Using these purified preparations, we determined that in vitro PrPres amplification was inhibited by CuCl 2 and ZnCl 2 at IC 50 concentrations of ∼400 n m and 10 μ m , respectively. In contrast, 100 μ m MnCl 2 did not directly inhibit PrPres amplification or block Cu 2+ ‐mediated inhibition. Additionally, the inhibition of PrPres amplification by Cu 2+ ions could be reversed by addition of either neocuproine or imidazole. Cu 2+ inhibited PrPres amplification in both the presence and absence of stimulatory polyanion molecules. These biochemical findings support the hypothesis that Cu 2+ ions might regulate the pathogenesis of prion diseases in vivo .