title: Prion infection impairs the cellular response to oxidative stress.
abstract: The molecular mechanism of neurodegeneration in transmissible spongiform encephalopathies remains uncertain. In this study, it was demonstrated that prion-infected hypothalamic neuronal GT1 cells displayed a higher sensitivity to induced oxidative stress over noninfected cells. In addition, the infected cells presented an increased lipid peroxidation and signs of apoptosis associated with a dramatic reduction in the activities of the glutathione-dependent and superoxide dismutase antioxidant systems. This study indicates for the first time that prion infection results in an alteration of the molecular mechanisms promoting cellular resistance to reactive oxygen species. This finding is vital for future therapeutic approaches in transmissible spongiform encephalopathies and the understanding of the function of the prion protein.
authors.affiliation: Institut de Génétique Humaine, Centre National de la Recherche Scientifique U.P.R. 1142, 141, rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors.forename: O
authors.initials: O
authors.lastname: Milhavet
authors.forename: H E
authors.initials: HE
authors.lastname: McMahon
authors.forename: W
authors.initials: W
authors.lastname: Rachidi
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.forename: S
authors.initials: S
authors.lastname: Katamine
authors.forename: A
authors.initials: A
authors.lastname: Mangé
authors.forename: M
authors.initials: M
authors.lastname: Arlotto
authors.forename: D
authors.initials: D
authors.lastname: Casanova
authors.forename: J
authors.initials: J
authors.lastname: Riondel
authors.forename: A
authors.initials: A
authors.lastname: Favier
authors.forename: S
authors.initials: S
authors.lastname: Lehmann
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D017096:Prion Diseases / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D013482:Superoxide Dismutase; D005978:Glutathione