NR APIH
AU Hutter,G.; Heppner,F.L.; Aguzzi,A.
TI No superoxide dismutase activity of cellular prion protein in vivo
QU Biological Chemistry 2003 Sep; 384(9): 1279-85
PT journal article
AB Prion diseases are characterized by the deposition of PrPsc, an abnormal form of the cellular prion protein PrPc, which is encoded by the Prnp gene. PrPc is highly expressed on neurons and its function is unknown. Recombinant PrPc was claimed to possess superoxide dismutase (SOD) activity, and it was hypothesized that abrogation of this function may contribute to neurodegeneration in prion diseases. We tested this hypothesis in vivo by studying copper/zinc and manganese SOD activity in genetically defined crosses of mice lacking the Sod1 gene with mice lacking PrPc, and with hemizygous or homozygous tga20 transgenic mice overexpressing various levels of PrPc. We failed to detect any influence of the Prnp genotype and gene dosage on SOD1 or SOD2 activity in heart, spleen, brain, and synaptosome-enriched brain fractions. Control experiments included crosses of mice lacking or overexpressing PrPc with mice overexpressing human Cu2+/Zn2+-superoxide dismutase, and confirmed that SOD enzymatic activity correlated exclusively with the gene dosage of bona fide human or murine SOD. We conclude that PrPc in vivo does not discernibly contribute to total SOD activity and does not possess an intrinsic dismutase activity.
MH Animals; Brain/cytology/ultrastructure; Gene Dosage; Human; Mice; Mice, Transgenic; PrPc Proteins/analysis/genetics/*metabolism; Prion Diseases/etiology; Superoxide Dismutase/analysis/genetics/*metabolism; Support, Non-U.S. Gov't; Synaptosomes/chemistry/enzymology; Tissue Distribution
AD Institute of Neuropathology, Schmelzbergstrasse 12, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
SP englisch
PO Deutschland