title: Prion infection impairs copper binding of cultured cells.
abstract: The molecular mechanism of neurodegeneration in transmissible spongiform encephalopathies (TSEs) remains unclear. Using radioactive copper ((64)Cu) at physiological concentration, we showed that prion infected cells display a marked reduction in copper binding. The level of full-length prion protein known to bind the metal ion was not modified in infected cells, but a fraction of this protein was not releasable from the membrane by phosphatidylinositol-specific phospholipase C. Our results suggest that prion infection modulates copper content at a cellular level and that modification of copper homeostasis plays a determinant role in the neuropathology of TSE.
authors.affiliation: Laboratoire Biologie Stress Oxydant, Faculté de Pharmacie, Domaine de La Merci, 38706 La Tronche-Grenoble, France.
authors.forename: Walid
authors.initials: W
authors.lastname: Rachidi
authors.forename: Alain
authors.initials: A
authors.lastname: Mangé
authors.forename: Abderrahmene
authors.initials: A
authors.lastname: Senator
authors.forename: Pascale
authors.initials: P
authors.lastname: Guiraud
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Riondel
authors.forename: Mustapha
authors.initials: M
authors.lastname: Benboubetra
authors.forename: Alain
authors.initials: A
authors.lastname: Favier
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
mesh_terms: D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D003301:Copper Radioisotopes; D006801:Humans; D007700:Kinetics; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D017096:Prion Diseases / Q000209:etiology / Q000378:metabolism*; D011328:Prions / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D003301:Copper Radioisotopes; D011328:Prions; D003300:Copper; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase