Prion protein expression and superoxide dismutase activity

Abstract

The function of the prion protein (PrP(c)) remains uncertain. It has been suggested that prion protein expression may aid cellular resistance to oxidative stress by influencing the activity of Cu/Zn superoxide dismutase (Cu,Zn SOD). The activity of Cu,Zn SOD was investigated in mice with different levels of PrP(c) expression. Increasing levels of PrP(c) expression were linked to increased levels of Cu,Zn SOD activity. Western-blot and Northern-blot analysis indicated that mice either lacking or overexpressing PrP(c) had levels of Cu,Zn SOD mRNA equivalent to those expressed in wild-type mice. Mice overexpressing the prion protein had lower levels of resistance to oxidative stress but higher expression levels of glutathione peroxidase, probably due to increased levels of hydrogen peroxide produced by increased Cu,Zn SOD activity. When cells were metabolically labelled with radioactive copper, increased radioactivity was immunoprecipitated with Cu,Zn SOD from mice with higher levels of PrP(c). In addition, diethyl-dithiocarbamate, a copper chelator that inactivates Cu,Zn SOD by capturing copper from the molecule, is more able to inactivate Cu,Zn SOD expressed in animals with higher levels of PrP(c). As recent studies have suggested that PrP(c) may regulate some aspect of copper metabolism, it is suggested that PrP(c) expression may regulate Cu,Zn SOD activity by influencing copper incorporation into the molecule.