Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein.
Although minor abnormalities have been reported in prion protein (PrP) knock-out (Prnp-/-) mice, the normal physiological function of PrP, the causative agent implicated in transmissible spongiform encephalopathies (TSE), remains unresolved. Since there are increasing correlations between oxidative stress and amyloidoses, we decided to investigate whether PrP plays a role in oxidative modulation. We found higher levels of oxidative damage to proteins and lipids in the brain lysates of Prnp-/- as compared to wild-type (WT) mice of the same genetic background. These two indicators, protein oxidation and lipid peroxidation, are hallmarks of cellular oxidative damage. Elevated levels of ubiquitin-protein conjugates were also observed in Prnp-/- mice, a probable consequence of cellular attempts to remove the damaged proteins as indicated by increased proteasome activity. Taken together, these findings are indicative of a role for PrP in oxidative homeostasis in vivo.
Wong
B S
BS
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Liu
T
T
Li
R
R
Pan
T
T
Petersen
R B
RB
Smith
M A
MA
Gambetti
P
P
Perry
G
G
Manson
J C
JC
Brown
D R
DR
Sy
M S
MS
D000447:Aldehydes / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D007659:Ketones / Q000032:analysis; D015227:Lipid Peroxidation; D008055:Lipids / Q000737:chemistry; D046911:Macromolecular Substances; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D018621:PrPC Proteins / Q000172:deficiency* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry
D000447:Aldehydes; D015415:Biomarkers; D007659:Ketones; D008055:Lipids; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D018621:PrPC Proteins; D011506:Proteins; D025801:Ubiquitin; D008315:Malondialdehyde; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex