The specificity of neuroprotection by antioxidants

Abstract

BackgroundReactive oxygen species (ROS) play an important role in aging and age-related diseases such as Parkinson's disease and Alzheimer's disease. Much of the ROS production under conditions of toxic stress is from mitochondria, and multiple antioxidants prevent ROS accumulation. The aim of this study is to examine the specificity of the interaction between the antioxidants and ROS production in stressed cells.MethodsUsing fluorescent dyes for ROS detection and mitochondrial inhibitors of known specificities, we studied ROS production under three conditions where ROS are produced by mitochondria: oxidative glutamate toxicity, state IV respiration induced by oligomycin, and tumor necrosis factor-induced cell death.ResultsWe demonstrated that there are at least four mitochondrial ROS-generating sites in cells, including the flavin mononucleotide (FMN) group of complex I and the three ubiquinone-binding sites in complexes I, II and III. ROS production from these sites is modulated in an insult-specific manner and the sites are differentially accessible to common antioxidants.ConclusionThe inhibition of ROS accumulation by different antioxidants is specific to the site of ROS generation as well as the antioxidant. This information should be useful for devising new interventions to delay aging or treat ROS-related diseases.

Sequential Upregulation of Superoxide Dismutase 2 and Heme Oxygenase 1 by tert-Butylhydroquinone Protects Mitochondria during Oxidative Stress

“…2) prompted us to investigate the regulation of tBHQ on ETC function. As previously reported, oligomycin impedes the conversion of ADP to ATP and induces a burst of cellular ROS levels (.10-fold) in HT-22 tBHQ Protects Mitochondria under Oxidative Stress cells (Liu and Schubert, 2009). Similarly, inhibition of mitochondrial complex I activity by rotenone leads to a 3-fold increase in ROS, and cell death in HT-22 cells (Panee et al, 2007;Poteet et al, 2012).…”

Calcium-dependent phospholipase A2modulates infection-induced diaphragm dysfunction

“…The first technique we employed to assess mitochondrial free radical formation involved measurement of fluorescence following incubation of C2C12 cell with MitoSox, a mitochondrially targeted derivative of hydroethidine. This molecule localizes to mitochondria and reacts with superoxide to form a product with a characteristic fluorescent signature (17). We found that addition of cytokines to C2C12 cells resulted in an increase in the MitoSox fluorescent signal.…”

Cells Lacking Rieske Iron-Sulfur Protein Have a Reactive Oxygen Species-Associated Decrease in Respiratory Complexes I and IV

“…7A and B, respectively). Previous studies have shown that oligomycin and antimycin A markedly increase ROS generation, whereas KCN does not (44).…”