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Effects of Copper on Survival of Prion Protein Knockout Neurons and Glia
Author(s) -
Brown David R.,
Schmidt Bernhard,
Kretzschmar Hans A.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70041686.x
Subject(s) - prnp , toxicity , oxidative stress , cerebellum , biology , biochemistry , microbiology and biotechnology , copper toxicity , chemistry , endocrinology , gene , allele , organic chemistry
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 (Prnp 0/0 mice) are more sensitive to copper toxicity and oxidative stress. PrPOcta selectively promotes the survival of Prnp 0/0 cerebellar cells. However, PrPOcta also reduces the toxicity of CuSO 4 on cerebellar cells and abolishes the difference in increased sensitivity of Prnp 0/0 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.