Prion diseases are fatal neurodegenerative disorders resulting from conform
ational changes in the prion protein from its normal cellular isoform, PrPC
, to the infectious scrapie isoform, PrPSc. In spite of many studies, the p
hysiological function of PrPC remains unknown. Recent work shows that PrPC
binds Cu2+. internalizing it into the cytoplasm. Since many antioxidant enz
ymes depend on Cu2+ (e.g., Cu/ZnSOD), their function could be affected in p
rion diseases. Here we investigate a possible relationship between PrPC and
the cellular antioxidant systems in different structures isolated from PrP
C knockout and wild-type mice by determining oxidative damage in protein an
d lipids and activity of antioxidant enzymes (CAT, SOD) and stress-adaptive
enzymes (ODC). Our results show that. in the absence of PrPC, there is an
increased oxidation of lipid and protein in all structures investigated. De
creased SOD activity and changes in CAT/ODC activities were also observed.
Taking into account these results, we suggest that the physiological functi
on of PrPC is related to cellular antioxidant defenses. Therefore, during d
evelopment of prion diseases, the whole organism becomes more sensitive to
ROS injury, leading to a progressive oxidative disruption of tissues and vi
tal organs, especially the central nervous system. (C) 2001 Elsevier Scienc
e Inc.