title: Basal brain oxidative and nitrative stress levels are finely regulated by the interplay between superoxide dismutase 2 and p53.
abstract: Superoxide dismutases (SODs) are the primary reactive oxygen species (ROS)-scavenging enzymes of the cell and catalyze the dismutation of superoxide radicals O2- to H2O2 and molecular oxygen (O2). Among the three forms of SOD identified, manganese-containing SOD (MnSOD, SOD2) is a homotetramer located wholly in the mitochondrial matrix. Because of the SOD2 strategic location, it represents the first mechanism of defense against the augmentation of ROS/reactive nitrogen species levels in the mitochondria for preventing further damage. This study seeks to understand the effects that the partial lack (SOD2(-/+) ) or the overexpression (TgSOD2) of MnSOD produces on oxidative/nitrative stress basal levels in different brain isolated cellular fractions (i.e., mitochondrial, nuclear, cytosolic) as well as in the whole-brain homogenate. Furthermore, because of the known interaction between SOD2 and p53 protein, this study seeks to clarify the impact that the double mutation has on oxidative/nitrative stress levels in the brain of mice carrying the double mutation (p53(-/-) × SOD2(-/+) and p53(-/-) × TgSOD2). We show that each mutation affects mitochondrial, nuclear, and cytosolic oxidative/nitrative stress basal levels differently, but, overall, no change or reduction of oxidative/nitrative stress levels was found in the whole-brain homogenate. The analysis of well-known antioxidant systems such as thioredoxin-1 and Nrf2/HO-1/BVR-A suggests their potential role in the maintenance of the cellular redox homeostasis in the presence of changes of SOD2 and/or p53 protein levels.
authors.affiliation: Department of Biochemical Sciences "A. Rossi-Fanelli,", Sapienza University of Rome, Roma, Italy.|Facultad de Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Providencia, Santiago, Chile.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Barone
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, Kentucky.|Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky.|Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenini
authors.affiliation: Department of Biochemical Sciences "A. Rossi-Fanelli,", Sapienza University of Rome, Roma, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.affiliation: Markey Cancer Center, University of Kentucky, Lexington, Kentucky.|Department of Toxicology, University of Kentucky, Lexington, Kentucky.
authors.forename: Teresa
authors.initials: T
authors.lastname: Noel
authors.affiliation: Biostatistics Core, Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Chi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biochemical Sciences "A. Rossi-Fanelli,", Sapienza University of Rome, Roma, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.affiliation: Markey Cancer Center, University of Kentucky, Lexington, Kentucky.|Department of Toxicology, University of Kentucky, Lexington, Kentucky.
authors.forename: Daret K
authors.initials: DK
authors.lastname: St Clair
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, Kentucky.|Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky.|Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000378:metabolism; D015538:Nitrosation; D018384:Oxidative Stress / Q000502:physiology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; D000099156:Superoxide Dismutase 2
keywords: MnSOD; p53; RRID:AB_10618757; RRID:AB_10850321; RRID:AB_1840351; RRID:AB_2049199; RRID:AB_2256876; RRID:AB_476744; RRID:AB_881705; RRID:AB_958795; biliverdin reductase-A; heme oxygenase-1; oxidative stress