title: Copper brain protein protection against free radical-induced neuronal death: Survival ratio in SH-SY5Y neuroblastoma cell cultures.
abstract: In Creutzfeldt Jakob, Alzheimer and Parkinson diseases, copper metalloproteins such as prion, amyloid protein precursor and α-synuclein are able to protect against free radicals by reduction from cupric Cu+2to cupreous Cu+. In these pathologies, a regional copper (Cu) brain decrease correlated with an iron, zinc or manganese (Mn) increase has previously been observed, leading to local neuronal death and abnormal deposition of these metalloproteins in β-sheet structures. In this study we demonstrate the protective effect of Cu metalloproteins against deleterious free-radical effects. With neuroblastoma SH-SY5Y cell cultures, we show that bovine brain prion protein in Cu but not Mn form prevents free radical-induced neuronal death. The survival ratio of SH-SY5Y cells has been measured after UV irradiation (free radical production), when the incubating medium is supplemented with bovine brain homogenate in native, Cu or Mn forms. This ratio, about 28% without any addition or with bovine brain protein added in Mn form, increases by as much as 54.73% with addition to the culture medium of native bovine brain protein and by as much as 95.95% if the addition is carried out in cupric form. This protective effect of brain copper protein against free radical-induced neuronal death has been confirmed with Inductively Coupled Plasma Mass Spectrometry Mn and Cu measurement in bovine brain homogenates: respectively lower than detection limit and 9.01μg/g dry weight for native form; lower than detection limit and 825.85μg/g dry weight for Cu-supplemented form and 1.75 and 68.1μg/g dry weight in Mn-supplemented brain homogenate.
authors.affiliation: Université François Rabelais de Tours, Toxicology Laboratory Faculty of Pharmacy, 31 Avenue Monge, 37200 Tours, France. Electronic address: roger.deloncle@univ-tours.fr.
authors.forename: Roger
authors.initials: R
authors.lastname: Deloncle
authors.affiliation: GREVIC, EA 3808, Biology and Health Pole, 86022 Poitiers, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Fauconneau
authors.affiliation: University of Poitiers, Faculty of Medicine and Pharmacy, 86000 Poitiers, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Guillard
authors.affiliation: Touraine Laboratory, Indre et Loire General Council, BP 67357- 37073 Tours Cedex 02, France.
authors.forename: José
authors.initials: J
authors.lastname: Delaval
authors.affiliation: Université François Rabelais de Tours, Virology-Immunology Laboratory Faculty of Pharmacy, 31 Avenue Monge, 37200 Tours, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lesage
authors.affiliation: Université de Nantes, Toxicology Laboratory Faculty of Pharmacy, 9 Rue Bias, BP 53508- 44035 Nantes Cedex 1, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Pineau
mesh_terms: D000818:Animals; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology; D009447:Neuroblastoma / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D000072002:Prion Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D005609:Free Radicals; D000072002:Prion Proteins; D008345:Manganese; D003300:Copper
keywords: Copper; Free radicals; Inductively Coupled Plasma Mass Spectrometry (ICP-MS); Manganese; Neuronal death; SH-SY5Y cells