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Selective superoxide dismutase (SOD) mimetics are potentially useful in pathological conditions in which there is an overproduction of the superoxide anion O2.-. These pathological conditions include inflammation, ischemia/reperfu...
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Selective superoxide dismutase (SOD) mimetics are potentially useful in pathological conditions in which there is an overproduction of the superoxide anion O2.-. These pathological conditions include inflammation, ischemia/reperfusion, shock, various cardiovascular disorders, amyotrophic lateral sclerosis (ALS) and other neurode-generative disorders. A major step forward in this field was the development of small-molecule selective SOD mimetics that penetrate cell membranes. These selective SOD mimetics catalytically remove O2.- without interfering with nitric oxide (NO), peroxynitrite (ONOO-) or other radicals such as hydroxyl radical or hydrogen peroxide (H2O2). These selective SOD mimetics (SC-52608, SC-55858, M-40403 and M-40401) have been shown to have benefits in animal models of inflammation, ischemia/reperfusion, shock, thrombosis and diabetes. The next challenge with selective SOD mimetics is to develop therapeutic potential into therapeutic agents.
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Superoxide, O_2~(?-), is formed in all living organisms that come in contact with air, and, depending upon its biological context, it may act as a signaling agent, a toxic species, or a harmless intermediate that decomposes sponta...
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Superoxide, O_2~(?-), is formed in all living organisms that come in contact with air, and, depending upon its biological context, it may act as a signaling agent, a toxic species, or a harmless intermediate that decomposes spontaneously. Its levels are limited in vivo by two different types of enzymes, superoxide reductase (SOR) and superoxide dismutase (SOD). Although superoxide has long been an important factor in evolution, it was not so when life first emerged on Earth at least 3.5 billion years ago. At that time, the early biosphere was highly reducing and lacking in any significant concentrations of dioxygen (O_2), very different from what it is today. Consequently, there was little or no O_2~(?-) and therefore no reason for SOR or SOD enzymes to evolve. Instead, the history of biological O_2~(?-) probably commences somewhere around 2.4 billion years ago, when the biosphere started to experience what has been termed the "Great Oxidation Event", a transformation driven by the increase in O_2 levels, formed by cyanobacteria as a product of oxygenic photosynthesis.1 The rise of O_2 on Earth caused a reshaping of existing metabolic pathways, and it triggered the development of new ones.2 Its appearance led to the formation of the so-called "reactive oxygen species" (ROS), for example, superoxide, hydrogen peroxide, and hydroxyl radical, and to a need for antioxidant enzymes and other antioxidant systems to protect against the growing levels of oxidative damage to living systems.
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to-baccoBright Yellow 2 (BY-2) suspension culture to understand the mechanisms of metal resistance in plant cells.We have analysed superoxide dismutase, catalase, and ascorbate peroxidase enzyme activities and superoxidedismutase-...
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to-baccoBright Yellow 2 (BY-2) suspension culture to understand the mechanisms of metal resistance in plant cells.We have analysed superoxide dismutase, catalase, and ascorbate peroxidase enzyme activities and superoxidedismutase-isoforms by isoelectric focusing gels in tobacco cells grown at two different toxic concentrations ofeach of the transition metals: copper, iron, manganese and zinc. Exposure of tobacco cells to these metals causedchanges in total superoxide dismutase activity in a different manner, depending on the metal assayed: after cop-perand manganese treatments, total superoxide dismutase activity was enhanced, while it was reduced after ironand zinc exposure. Superoxide dismutase-isoforms were affected by the metal used, and a Fe-SOD band with thesame isoelectric point as a Cu, Zn-SOD from non-treated cells, was induced after iron and zinc treatments. Cu,Zn-SODs were present in all metal-treatments whereas Mn-SOD was not detected in any case. Concerning otherantioxidant enzymes tested, such as catalase and ascorbate peroxidase, the latter showed a remarkable increase inactivity in response to copper treatments and catalase activity was enhanced after iron and with the lowest man-ganeseconcentration. Lipid peroxidation was increased after each metal treatment, as an indication of the oxi-dativedamage caused by metal concentration assayed in tobacco cells. These results suggest that an activation ofsome antioxidant enzymes in response to oxidative stress induced by transition metals is not enough to confertolerance to metal accumulation.
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A rapid and sensitive FIA method for superoxide dismutase (SOD) activity was developed using the chemiluminescence of lucigenin, which is specific to superoxide anion (Of). The immobilized xanthine oxidase in a reactor was used to...
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A rapid and sensitive FIA method for superoxide dismutase (SOD) activity was developed using the chemiluminescence of lucigenin, which is specific to superoxide anion (Of). The immobilized xanthine oxidase in a reactor was used to generate O~ and hypoxanthine was selected as the substrate. In the absence of SOD, the maximum amount of lucigenin reduced with 02 is observed (control). The presence of SOD suppresses the reduction of lucigenin. Therefore, the suppression ratio against the control can be regarded as being the inhibition ratio of each sample. Under the optimum conditions, the concentration of the SOD preparation giving 50% inhibition (IC5o) was <200 ng/ml (about 3.6 ng per injection) and the sampling frequency was about 60 samples/h. No tendency of the response to decrease was recognized by 200 repetitive injections. As another approach, a double-line flow system was constructed in which a caiTier stream containing hypoxanthine and lucigenin was fed into the enzyme reactor after confluence with a sample stream. Optimized conditions were examined and the performance was compared with that of the above single line system. When the SOD activity in erythrocytes of rats was determined by the present FIA method, the values were linearly related to those obtained by the conventional nitroblue tetrazolium (NBT) assay (r=0.980, n=19).
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For more than 30 years, the only enzymatic system known to catalyze the elimination of superoxide was superoxide dismutase, SOD. SOD has been found in almost all organisms living in the presence of oxygen, including some anaerobic...
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For more than 30 years, the only enzymatic system known to catalyze the elimination of superoxide was superoxide dismutase, SOD. SOD has been found in almost all organisms living in the presence of oxygen, including some anaerobic bacteria, supporting the notion that superoxide is a key and general component of oxidative stress. Recently, a new concept in the field of the mechanisms of cellular defense against superoxide has emerged. It was discovered that elimination of superoxide in some anaerobic and microaerophilic bacteria could occur by reduction, a reaction catalyzed by a small metalloenzyme thus named superoxide reductase, SOR. Having played a major role in this discovery, we describe here how the concept of superoxide reduction emerged and how it was experimentally substantiated independently in our laboratory.
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Diabetic nephropathy, the leading cause of end-stage renal disease, is characterized by a proapoptotic and prooxidative environment. The mechanisms by which lifestyle interventions, such as exercise, benefit diabetic nephropathy a...
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Diabetic nephropathy, the leading cause of end-stage renal disease, is characterized by a proapoptotic and prooxidative environment. The mechanisms by which lifestyle interventions, such as exercise, benefit diabetic nephropathy are unknown. We hypothesized that exercise inhibits early diabetic nephropathy via attenuation of the mitochondrial apoptotic pathway and oxidative damage. Type 2 diabetic db/db and normoglycemic wild-type mice were exercised for an hour everyday at a moderate intensity for 7 wk, following which renal function, morphology, apoptotic signaling, and oxidative stress were evaluated. Exercise reduced body weight, albuminuria, and pathological glomerular expansion in db/db mice independent of hyperglycemic status. Changes in renal morphology were also related to reduced caspase-3 (main effector caspase in renal apoptosis), caspase-8 (main initiator caspase of the "extrinsic" pathway) activities, and TNF-α expression. A role for the mitochondrial apoptotic pathway was unlikely as both caspase-9 activity (initiator caspase of this pathway) and expression of regulatory proteins such as Bax and Bcl-2 were unchanged. Kidneys from db/db mice also produced higher levels of superoxides and had greater oxidative damage concurrent with downregulation of superoxide dismutase (SOD) 1 and 3. Interestingly, although exercise also increased superoxides, there was also upregulation of multiple SODs that likely inhibited lipid (hydroperoxides) and protein (carbonyls and nitrotyrosine) oxidation in db/db kidneys. In conclusion, exercise can inhibit progression of early diabetic nephropathy independent of hyperglycemia. Reductions in caspase-3 and caspase-8 activities, with parallel improvements in SOD expression and reduced oxidative damage, could underlie the beneficial effects of exercise in diabetic kidney disease.
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Much of the toxicity of Hb has been linked to its redox activity; Hb may generate reactive oxygen species, such as the superoxide anion. Superoxide is intrinsically toxic, and superoxide dismutase (SOD) provides important cellular...
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Much of the toxicity of Hb has been linked to its redox activity; Hb may generate reactive oxygen species, such as the superoxide anion. Superoxide is intrinsically toxic, and superoxide dismutase (SOD) provides important cellular protection. However, if the Hb molecule is located outside the red blood cell, the normal protection systems involving SOD and catalase are no longer closely associated with it, exposing Hb and its cellular surroundings to oxidative damage. In order to produce less toxic Hb molecules, we have explored gene fusion to obtain homogeneous SOD-Hb conjugates. The chimeric protein was generated by coexpressing the human Hb l-chain/manganese SOD gene together with the o-chain gene in Escherichia coli. We show that the engineered SOD-Hb fusion protein retains the oxygen-binding capacity and, moreover, decreases cytotoxic ferrylHb (HbFet) formation when challenged with superoxide radicals. The SOD-Hb fusion protein also exhibits a 44% lower autoxidation rate and higher thermal stability than Hb alone.
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Физиологическая роль внеклеточной супероксиддисмутазы (СОДЗ) изучена недостаточно. Мы исследовали гипотезу, что СОДЗ, нейтра...
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Физиологическая роль внеклеточной супероксиддисмутазы (СОДЗ) изучена недостаточно. Мы исследовали гипотезу, что СОДЗ, нейтрализуя супероксиданионы (O_2~-) в меж-клетоточной среде головного мозга, предохраняет инактивацию оксида азота (N0) и таким способом вовлекается в регуляцию тонуса церебральных сосудов. У наркотизированных крыс измерялся локальный мозговой кровоток в стриатуме при введении в него в различных комбинациях СОД-миметика, СОД-ингибитора, NO-донора и NOS-ингибитора с помощью микродиализа. Показано, что в нормальных условиях СОДЗ минимизирует содержание O_2~-, сохраняя эндогенно продуцируемый N0 на уровне, достаточном для поддержания тонуса и реактивности мозговых сосудов. Установлено, что СОДЗ усиливает вазоди-лататорный эффект эндогенно продуцируемого N0 в мозгу. Показано, что СОДЗ способна нейтрализовать супероксиданионы, продуцируемые в мозгу при дыхании 100 % O_2, и сохранять базальный уровень NO и его вазодилататорную потенцию при нормобарической гипероксии.
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Copper toxicity in soil was evaluated using biomarkers of oxidative stress (catalase enzyme activity, superoxide dismutase and lipid peroxidation) in the earthworm Eisenia foetida. Agricultural topsoils from mining areas of the Ac...
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Copper toxicity in soil was evaluated using biomarkers of oxidative stress (catalase enzyme activity, superoxide dismutase and lipid peroxidation) in the earthworm Eisenia foetida. Agricultural topsoils from mining areas of the Aconcagua river basin were collected. Total copper concentrations were in the range of 94-959 mg kg~(-1), while the exchangeable copper concentrations were in the range of 46-2225 pg kg~(-1). Earthworms exposed to soil with exchangeable copper concentrations above 32 pg kg~(-1) showed an increase in catalase activity. Parameters of antioxidant activity were more sensitive than the weight change and thus can be used as appropriate biomarkers in Eisenia foetida.
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