It takes 2 antioxidants to tango: the interaction between manganese superoxide dismutase and glutathione peroxidase-1

Abstract

The generation of ATP via oxidative phosphorylation provides the energy required by aerobic organisms to sustain themselves. This process is localized to the mitochondria, where electrons are passed among the components of the electron transport chain where there is an inevitability of leakage of the highly reactive oxygen species (ROS) superoxide, with it having been estimated that 1%-2% of the oxygen being used for mitochondrial respiration is converted to superoxide. With its short halflife and extreme reactivity, there is a strong potential for the superoxide radical to interact with biomolecules, resulting in oxidative damage that could have a profound effect on cellular function and survivability. As described below, eukaryotic cells have evolved defense mechanisms to protect themselves from the adverse effects of superoxide accumulation and the strategic location of manganese superoxide dismutase (MnSOD) in the mitochondria is a principle one of these. As a consequence of the dismutation of superoxide by MnSOD, the less reactive hydrogen peroxide (H 2 O 2 ) is generated, which can diffuse through the mitochondrial membrane where it can have its own host of biological consequences. The management of the appropriate levels of ROS is the domain of a host of antioxidant molecules such as glutathione and enzymes that can neutralize ROS. Oxidative stress occurs when the levels of ROS exceed the cell's abilities to maintain them at their appropriate levels. While less considered, the elimination of ROS past the ideal levels to support cellular function may also occur, and this has been referred to as reductive stress. ROS as important signaling moleculesAerobic organisms have not only evolved to take advantage of the enhanced energy production that can be achieved by the consumption of oxygen via the electron transport chain, but have also evolved to use ROS as potent signaling molecules. Fluctuations in ROS can be due to changes in environmental stimuli or intrinsic metabolic activity, and examples abound throughout phylogeny indicating the sensing of and response to one ROS, H 2 O 2 . As examples, plants use an oxidative burst that generates H 2 O 2 that serves as a diffusible signal to induce apoptosis in pathogenexposed cells while stimulating antioxidant enzymes in adjacent tissues (Levine et al., 1994), and a H 2 O 2 gradient generated at the tissue level in zebrafish mediates wound healing and leukocyte recruitment (Niethammer et al., 2009). One of the first examples of H 2 O 2 being critical for normal mammalian functions was the demonstration that the production of H 2 O 2 could stimulate platelet-Abstract: Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD),...

The cytotoxic activity of sanguinarine in C32 human amelanotic melanoma cells

“…Furthermore, the insignificant decrease in GPX activity suggested that the quantity of hydrogen peroxide formed was high, and CAT was the most important factor in its removal. In addition, an important interaction between manganese SOD and GPX-1 was described in human cancer cells (Ekoue and Diamond, 2014). The elevated MDA level compared with the significant decrease in GST-specific activity indicated that this enzymatic activity was involved in MDA detoxification in an inefficient way.…”

Organ-specific antioxidant defenses and FT-IR spectroscopy of muscles inCrucian carp (Carassius auratus gibelio) exposed to environmental Pb2+

“…Previously, 35% inhibition in SOD activity in the liver tissue of S. aurata was attributed to the extension of lesions in the liver and drastic lipid infiltration in adipocytes due to Cd exposure (Souid et al, 2013). SOD activation may be due to excessive generation of ROS or inhibition as a result of direct damage to the SOD protein by increased H 2 O 2 content in the cell, whereas tissue-specific changes in SOD activity might be species-dependent (Ahmad et al, 2004;Puerto et al, 2010;Ekoue and Diamond, 2014). The activity of GPx can also be considered complementary to the activity of CAT, which is supported by the present data.…”

Role of glucose repression in the oxidative stress response ofSchizosaccharomyces pombe: analysis of transcript levels of fbp1, hxk2, sod1and ctt1 genes in sty1, atf1 and pap1 knock-out mutants

“…Next, we analyzed the transcript levels of genes encoding cellular antioxidants in eukaryotic cells from yeast to mammalian (Ekoue and Diamond, 2014). The transcript levels of sod1 and ctt1, encoding superoxide dismutase and catalase, respectively, were analyzed in ird5 double mutants and 972 wild-type single mutants.…”