title: Effects of copper on survival of prion protein knockout neurons and glia.
abstract: The N-terminal region of the prion protein (PrP) contains an octameric repeat region suggested to bind copper. A 32-amino acid peptide (PrPOcta) based on this region in the protein was tested for its effects on cultured cerebellar cells. Cerebellar cells from mice deficient in cellular PrP (Prnp0/0 mice) are more sensitive to copper toxicity and oxidative stress. PrPOcta selectively promotes the survival of Prnp0/0 cerebellar cells. However, PrPOcta also reduces the toxicity of CuSO4 on cerebellar cells and abolishes the difference in increased sensitivity of Prnp0/0 cells to both copper toxicity and also oxidative stress from xanthine oxidase. PrPOcta does not promote the survival or proliferation of astrocytes or microglia. The survival-promoting effects of PrPOcta on neurons may be due to its ability to effectively chelate copper. The octameric repeat region of PrP may represent a functional domain of the native protein.
authors.affiliation: Institut für Neuropathologie, Biochemie II, Universität Göttingen, Germany.
authors.forename: D R
authors.initials: DR
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: H A
authors.initials: HA
authors.lastname: Kretzschmar
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D003300:Copper / Q000494:pharmacology* / Q000506:poisoning; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011328:Prions / Q000235:genetics* / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D011328:Prions; D003300:Copper