Antioxidant activity related to copper binding of native prion protein

Abstract

We have developed a method to affinity-purify mouse prion protein (PrPc) from mouse brain and cultured cells. PrPc from mouse brain bound three copper atoms; PrPc from cultured cells bound between one and four copper atoms depending on the availability of copper in the culture medium. Purified PrPc exhibited antioxidant activity, as determined by spectrophotometric assay. Incubation of PrPc with the neurotoxic peptide, PrP106-126, inactivated the superoxide dismutase-like activity. Culture experiments showed that PrPc protects cells against oxidative stress relative to the amount of copper it binds. These results suggest that PrPc is a copper-binding protein which can incorporate varying amounts of copper and exhibit protective antioxidant activity.