Prion protein suppresses perturbation of cellular copper homeostasis under oxidative conditions.
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.
Sakudo
Akikazu
A
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Lee
Deug-chan
DC
Yoshimura
Etsuro
E
Nagasaka
Seiji
S
Nitta
Kayako
K
Saeki
Keiichi
K
Matsumoto
Yoshitsugu
Y
Lehmann
Sylvain
S
Itohara
Shigeyoshi
S
Sakaguchi
Suehiro
S
Onodera
Takashi
T
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
D000975:Antioxidants; D058851:GPI-Linked Proteins; D018621:PrPC Proteins; D011328:Prions; C122036:Prnd protein, mouse; D008345:Manganese; D003300:Copper