title: Prion protein suppresses perturbation of cellular copper homeostasis under oxidative conditions.
abstract: Prion protein (PrP) binds copper and exhibits superoxide dismutase-like activity, while the roles of PrP in copper homeostasis remain controversial. Using Zeeman graphite furnace atomic absorption spectroscopy, we quantified copper levels in immortalized PrP gene (Prnp)-deficient neuronal cells transfected with Prnp and/or Prnd, which encodes PrP-like protein (PrPLP/Dpl), in the presence or absence of oxidative stress induced by serum deprivation. In the presence of serum, copper levels were not significantly affected by the expression of PrP and/or PrPLP/Dpl, whereas serum deprivation induced a decrease in copper levels that was inhibited by PrP but not by PrPLP/Dpl. The inhibitory effect of PrP on the decrease of copper levels was prevented by overexpression of PrPLP/Dpl. These findings indicate that PrP specifically stabilizes copper homeostasis, which is perturbed under oxidative conditions, while PrPLP/Dpl overexpression prevents PrP function in copper homeostasis, suggesting an interaction of PrP and PrPLP/Dpl and distinct functions between PrP and PrPLP/Dpl on metal homeostasis. Taken together, these results strongly suggest that PrP, in addition to its antioxidant properties, plays a role in stabilizing cellular copper homeostasis under oxidative conditions.
authors.affiliation: Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Akikazu
authors.initials: A
authors.lastname: Sakudo
authors.forename: Deug-chan
authors.initials: DC
authors.lastname: Lee
authors.forename: Etsuro
authors.initials: E
authors.lastname: Yoshimura
authors.forename: Seiji
authors.initials: S
authors.lastname: Nagasaka
authors.forename: Kayako
authors.initials: K
authors.lastname: Nitta
authors.forename: Keiichi
authors.initials: K
authors.lastname: Saeki
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Suehiro
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D003300:Copper / Q000378:metabolism*; D058851:GPI-Linked Proteins; D006706:Homeostasis; D008297:Male; D008345:Manganese / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000975:Antioxidants; D058851:GPI-Linked Proteins; D018621:PrPC Proteins; D011328:Prions; C122036:Prnd protein, mouse; D008345:Manganese; D003300:Copper