Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity.
The cellular function of the prion protein (PrPc), a cell surface glycoprotein expressed in neurones and astrocytes, has not been elucidated. Cell culture experiments reveal that cerebellar cells lacking PrPc are more sensitive to oxidative stress and undergo cell death more readily than wild-type cells. This effect is reversible by treatment with vitamin E. In vivo studies show that the activity of Cu/Zn superoxide dismutase is reduced in Prnp gene-ablated (Prnp0/0) mice. Constitutively high Mn superoxide dismutase activity in these animals may compensate for this loss of responsiveness to oxidative stress. These findings suggest that PrPc may influence the activity of Cu/Zn superoxide dismutase and may be important for cellular resistance to oxidative stress.
Brown
D R
DR
Institut für Neuropathologie, Universität Göttingen, Germany.
Schulz-Schaeffer
W J
WJ
Schmidt
B
B
Kretzschmar
H A
HA
D000595:Amino Acid Sequence; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004050:Ditiocarb / Q000494:pharmacology; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007527:Isoenzymes / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011190:Potassium Cyanide / Q000494:pharmacology; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000737:chemistry / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000172:deficiency / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
D007527:Isoenzymes; D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; D014810:Vitamin E; D018698:Glutamic Acid; D015759:Ionomycin; D004050:Ditiocarb; D013482:Superoxide Dismutase; D011190:Potassium Cyanide; D019331:NG-Nitroarginine Methyl Ester; D000640:Amitrole