Antioxidant activity related to copper binding of native prion protein.
We have developed a method to affinity-purify mouse prion protein (PrP(c)) from mouse brain and cultured cells. PrP(c) from mouse brain bound three copper atoms; PrP(c) from cultured cells bound between one and four copper atoms depending on the availability of copper in the culture medium. Purified PrP(c) exhibited antioxidant activity, as determined by spectrophotometric assay. Incubation of PrP(c) with the neurotoxic peptide, PrP106-126, inactivated the superoxide dismutase-like activity. Culture experiments showed that PrP(c) protects cells against oxidative stress relative to the amount of copper it binds. These results suggest that PrP(c) is a copper-binding protein which can incorporate varying amounts of copper and exhibit protective antioxidant activity.
Brown
D R
DR
Department of Biochemistry, Cambridge University, Cambridge, UK. drb33@cam.ac.uk
Clive
C
C
Haswell
S J
SJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002413:Cations, Divalent / Q000032:analysis; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003300:Copper / Q000378:metabolism*; D003574:Cytochrome c Group / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D018621:PrPC Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D011328:Prions / Q000378:metabolism / Q000494:pharmacology; D013052:Spectrometry, X-Ray Emission; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D000975:Antioxidants; D002413:Cations, Divalent; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; D013778:Tetrazolium Salts; D013844:Thiazoles; C082632:prion protein (106-126); D003300:Copper; D013482:Superoxide Dismutase; C022616:thiazolyl blue