title: Oxidized SOD1 alters proteasome activities in vitro and in the cortex of SOD1 overexpressing mice.
abstract: Premature ageing, one of the characteristics of Down syndrome (DS), may involve oxidative stress and impairment of proteasome activity. Transgenic mice overexpressing the human copper/zinc superoxide dismutase (SOD1) gene are one of the first murine models for DS and it has been shown that SOD1 overexpression might be either deleterious or beneficial. Here, we show a reduction in proteasome activities in the cortex of SOD1 transgenic mice and an associated increase in the content of oxidized SOD1 protein. As we demonstrate that in vitro oxidized SOD can inhibit purified proteasome peptidase activities, modified SOD1 might be partially responsible for proteasome inhibition shown in SOD1 transgenic mice.
authors.affiliation: EA3508, Modèles de dérégulation génique: Trisomie 21 et Hyperhomocysteinémie. Université Paris 7, Denis Diderot, Campus Jussieu, Tour 54, 2 étage, couloir 54/53, Case 7104, 2, place Jussieu, 75005 Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Le Pecheur
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourdon
authors.forename: Evelyne
authors.initials: E
authors.lastname: Paly
authors.forename: Luc
authors.initials: L
authors.lastname: Farout
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.forename: Jacqueline
authors.initials: J
authors.lastname: London
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology*; D004314:Down Syndrome / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex / Q000032:analysis / Q000378:metabolism*; D061988:Proteasome Inhibitors; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015533:Transcriptional Activation
chemical_list: D061988:Proteasome Inhibitors; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D046988:Proteasome Endopeptidase Complex