title: Prion protein prevents heavy metals overloading of cells and thus protects them against their toxicity.
abstract: Physiological function of a prion protein (PrP) is not known yet. Regarding the relation of PrP to heavy metals it is known that PrP is able to bind divalent ions of copper, zinc, manganese and nickel through its octarepeat region. It has been hypothesized but not yet confirmed that PrP could play a role in copper metabolism. In this study, cells expressing human full-length PrP (HuPrP1) and PrP-knockout (PrP0/0/1) cells were incubated with various concentrations of copper, zinc, manganese and nickel for 4 days and then were assayed for intracellular content of these metals and cell viability. The results showed that HuPrP1 cells accumulated less heavy metals than PrP0/0/1 cells when concentrations of heavy metals exceeded physiological level. In conclusion, HuPrP1 cells are more resistant to chronic overload with copper, manganese, zinc or nickel than PrP0/0/1 cells. The resistance to metals overload is caused solely by the presence of PrP, since HuPrP1 and PrP0/0/1 cells differ only in the expression of PrP. These results indicate that one of the functions of PrP can be the modulation of trace heavy metal concentrations in cells and protection of cells against heavy metals overload and subsequent oxidative stress.
authors.forename: M
authors.initials: M
authors.lastname: Prčina
authors.forename: E
authors.initials: E
authors.lastname: Kontseková
authors.forename: M
authors.initials: M
authors.lastname: Novák
mesh_terms: D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival; D003300:Copper / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008345:Manganese / Q000378:metabolism / Q000633:toxicity; D019216:Metals, Heavy / Q000378:metabolism / Q000633:toxicity*; D009532:Nickel / Q000378:metabolism / Q000633:toxicity; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism / Q000633:toxicity
chemical_list: D019216:Metals, Heavy; D018621:PrPC Proteins; D008345:Manganese; D003300:Copper; D009532:Nickel; D015032:Zinc
keywords: prion protein; copper; manganese; zinc; nickel; oxidative stress.