Brain copper content and cuproenzyme activity do not vary with prion protein expression level

Prion diseases are neurodegenerative disorders that result from conformatio nal transformation of a normal cell surface glycoprotein, PrPC, into a path ogenic isoform, PrPSc. Although the normal physiological function of PrPC h as remained enigmatic, the recent observation that the protein binds copper ions with micromolar affinity suggests a possible role in brain copper met abolism, In this study, we have used mice that express 0, 1, and 10 times t he normal level of PrP to assess the effect of PrP expression level on the amount of brain copper and on the properties of two brain cuproenzymes, Usi ng mass spectrometry, we find that the amount of ionic copper in subcellula r fractions from brain is similar in all three lines of mice. In addition, the enzymatic activities of Cu-Zn superoxide dismutase and cytochrome c oxi dase in brain extracts are similar in these groups of animals, as is the in corporation of Cu-64 into Cu-Zn superoxide dismutase both in cultured cereb ellar neurons and in vivo, Our results differ from those of another set of published studies, and they require a re-evaluation of the role of PrPC in copper metabolism.