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Basal brain oxidative and nitrative stress levels are finely regulated by the interplay between superoxide dismutase 2 and p53
Author(s) -
Barone Eugenio,
Cenini Giovanna,
Di Domenico Fabio,
Noel Teresa,
Wang Chi,
Perluigi Marzia,
St. Clair Daret K.,
Butterfield D. Allan
Publication year - 2015
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23627
Subject(s) - sod2 , oxidative stress , superoxide dismutase , reactive oxygen species , sod1 , chemistry , cytosol , mitochondrion , superoxide , biochemistry , mitochondrial ros , oxidative phosphorylation , microbiology and biotechnology , biology , enzyme
Superoxide dismutases (SODs) are the primary reactive oxygen species (ROS)‐scavenging enzymes of the cell and catalyze the dismutation of superoxide radicals O 2 – to H 2 O 2 and molecular oxygen (O 2 ). 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. © 2015 Wiley Periodicals, Inc.