This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor (VEGF) and nitric oxide (NO) signaling in vascular endothelium. We utilized a mouse model of neonatal hyperoxic lung injury and SOD3 knockout (KO) mice to evaluate its function during chronic hyperoxia exposure. Wild-type age-matched neonatal C57Bl/6 (WT) and SOD3-/- (KO) mice were placed in normoxia (21% FiO2, RA) or chronic hyperoxia (75% FiO2, O2) within 24 h of birth for 14 days continuously and then euthanized. Lungs were harvested for histologic evaluation, as well as comparison of antioxidant enzyme expression, SOD activity, VEGF expression, and portions of the NO signaling pathway. Surprisingly, KO-O2 mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O2 mice. KO-O2 mice had increased total SOD activity and increased VEGF expression when compared to WT-O2 mice. No genotype differences were noted in intracellular antioxidant enzyme expression or the NO signaling pathway. These results demonstrate that SOD3 KO mice can survive prolonged hyperoxia without exacerbation of alveolar or vascular phenotype.
Methylglyoxal (MG) is a highly reactive aldehyde spontaneously formed in human cells mainly as a by-product of glycolysis. Such endogenous metabolite reacts with proteins, nucleotides and lipids forming advanced glycation end-products (AGEs). MG binds to arginine, lysine and cysteine residues of proteins causing the formation of stable adducts that can interfere with protein function. Among the proteins affected by glycation, MG has been found to react with superoxide dismutase 1 (SOD1), a fundamental anti-oxidant enzyme that is abundantly expressed in neurons. Considering the high neuronal susceptibility to MG-induced oxidative stress, we sought to investigate by mass spectrometry and NMR spectroscopy which are the structural modifications induced on SOD1 by the reaction with MG. We show that MG reacts preferentially with the disulfide-reduced, demetallated form of SOD1, gradually causing its unfolding, and to a lesser extent, with the intermediate state of maturation - the reduced, zinc-bound homodimer - causing its gradual monomerization. These results suggest that MG could impair the correct maturation of SOD1 in vivo, thus both increasing cellular oxidative stress and promoting the cytotoxic misfolding and aggregation process of SOD1.
Cu/Zn superoxide dismutase (Cu/Zn SOD) is a key enzyme in the metabolism of oxygen free radicals. The gene resides on chromosome 21 and is overexpressed in patients with Down syndrome. Cultured neurons of transgenic Cu/Zn SOD (Tg-Cu/Zn SOD) mice with elevated activity of Cu/Zn SOD were used to determine whether constitutive overexpression of Cu/Zn SOD creates an indigenous oxidative stress that predisposes the Tg-Cu/Zn SOD neurons to added insults. Neurons from three independently derived Tg-Cu/Zn SOD strains showed higher susceptibility than nontransgenic neurons to kainic acid (KA)-mediated excitotoxicity, reflected by an earlier onset and enhanced apoptotic cell death. This higher susceptibility of transgenic neurons to KA-mediated apoptosis was associated with a chronic prooxidant state that was manifested by reduced levels of cellular glutathione and altered [Ca2+]i homeostasis. The data are compatible with the thesis that overexpression of Cu/Zn SOD creates chronic oxidative stress in the transgenic neurons, which exacerbates their susceptibility to additional insults such as KA-mediated excitotoxicity.
Helicobacter pylori increases production of reactive oxygen species (ROS), which activates inflammatory and carcinogenesis-related signaling pathways in gastric epithelial cells. Therefore, reducing ROS, by upregulating antioxidant enzyme, such as superoxide dismutase (SOD), may be a novel strategy to prevent H. pylori-associated gastric diseases. Astaxanthin is an antioxidant carotenoid that prevents oxidative stress-induced cell injury. The present study was aimed to determine whether H. pylori decreases SOD activity by changing the levels of SOD1/SOD2 and whether astaxanthin prevents changes in SOD levels and activity in H. pylori-infected gastric epithelial AGS cells.
Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here, we show that deficiency of the major mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) in the gastrointestinal tract drives spontaneous obesity. Intestinal epithelium-specific Sod2 ablation in mice induced adiposity and inflammation via phospholipase A2 (PLA2) activation and increased release of omega-6 polyunsaturated fatty acid arachidonic acid. Remarkably, this obese phenotype was rescued when fed an essential fatty acid-deficient diet, which abrogates de novo biosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinal Sod2 mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinal Sod2 levels, PLA2 activity, and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.
Superoxide dismutase (SOD) is one of the most important antioxidant enzymes present in all oxygen-metabolizing cells. This enzyme eliminates toxins from our body, so it is vital to understand its action and activity under the influence of different wavelengths. The effects of different wavelengths of light in the visible range on SOD activity were investigated.
Isoflavones are plant-derived natural products commonly found in legumes that show a large spectrum of biomedical activities. A common antidiabetic remedy in traditional Chinese medicine, Astragalus trimestris L. contains the isoflavone formononetin (FMNT). Literature reports show that FMNT can increase insulin sensitivity and potentially target the peroxisome proliferator-activated receptor gamma, PPARγ, as a partial agonist. PPARγ is highly relevant for diabetes control and plays a major role in Type 2 diabetes mellitus development. In this study, we evaluate the biological role of FMNT, and three related isoflavones, genistein, daidzein and biochanin A, using several computational and experimental procedures. Our results reveal the FMNT X-ray crystal structure has strong intermolecular hydrogen bonding and stacking interactions which are useful for antioxidant action. Cyclovoltammetry rotating ring disk electrode (RRDE) measurements show that all four isoflavones behave in a similar manner when scavenging the superoxide radical. DFT calculations conclude that antioxidant activity is based on the familiar superoxide σ-scavenging mode involving hydrogen capture of ring-A H7(hydroxyl) as well as the π-π (polyphenol-superoxide) scavenging activity. These results suggest the possibility of their mimicking superoxide dismutase (SOD) action and help explain the ability of natural polyphenols to assist in lowering superoxide concentrations. The SOD metalloenzymes all dismutate O2•- to H2O2 plus O2 through metal ion redox chemistry whereas these polyphenolic compounds do so through suitable hydrogen bonding and stacking intermolecular interactions. Additionally, docking calculations suggest FMNT can be a partial agonist of the PPARγ domain. Overall, our work confirms the efficacy in combining multidisciplinary approaches to provide insight into the mechanism of action of small molecule polyphenol antioxidants. Our findings promote the further exploration of other natural products, including those known to be effective in traditional Chinese medicine for potential drug design in diabetes research.
Reactive oxygen species play critical roles in a number of physiologic and pathologic processes. Nitroxides are stable free radical compounds that possess superoxide dismutase (SOD) mimetic activity and have been shown to protect against the toxicity of reactive oxygen species in vitro and in vivo. Tempol, a cell-permeable hydrophilic nitroxide, protects against oxidative stress and also is an in vitro and in vivo radioprotector. In the course of evaluating the pharmacology and toxicity of the nitroxides, Tempol and another nitroxide, 3-carbamoyl-PROXYL (3-CP), were administered intravenously in various concentrations to miniature swine. Tempol caused dose-related hypotension accompanied by reflex tachycardia and increased skin temperature. Invasive hemodynamic monitoring with Swan Ganz catheterization (SGC) confirmed the potent vasodilative effect of Tempol. However, 3-CP had no effect on porcine blood pressure. The hemodynamic effects of Tempol and 3-CP are discussed in the context of differential catalytic rate constants for superoxide disumation that may impact systemic nitric oxide (NO) levels and lead to vasodilation. These findings are consistent with a role for the superoxide ion in the modulation of blood pressure and have potential implications for the systemic use of nitroxides.
Oxidative damage is a major cause of lung injury during systemic inflammatory response syndrome. In this study, the expression of an antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), and its protective role against pulmonary oxidative damage were investigated using mouse models of systemic inflammation. Intraperitoneal injection with bacterial endotoxin lipopolysaccharides (LPS; 20 mg/kg) caused oxidative damage in lungs as assessed by increased tyrosine nitration in proteins. LPS administration also resulted in a rapid and significant loss of more than 80% of pulmonary EC-SOD in a time- and dose-dependent manner, but other types of SODs, cytoplasmic CuZn-SOD and mitochondrial Mn-SOD, were not affected. EC-SOD protein is most abundant in lungs but also present at high levels in other tissues such as heart and white fat; however, the LPS-mediated decrease in this enzyme was most apparent in the lungs. Intravenous injection of mice with tumor necrosis factor alpha (10 microg per mouse) also caused a 60% decrease in EC-SOD in the lungs, suggesting that the EC-SOD down-regulation is mediated by this LPS-inducible inflammatory cytokine. A protective role for EC-SOD against LPS-mediated systemic inflammation was shown by an increased survival rate (75% vs 29% in 5 days) and decreased pulmonary oxidative damage in EC-SOD transgenic mice that overexpress the human EC-SOD gene. These results demonstrate that the inflammation-mediated EC-SOD down-regulation has a major pathophysiological impact during the systemic inflammatory response syndrome.
The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10-100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91phox, Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO2-induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.
Allergic conjunctivitis is an inflammatory eye disease mediated by Th2 type immune response. The role of extracellular superoxide dismutase 3 (SOD3) in immune response and allergic conjunctival inflammation was examined in a murine model for experimental allergic conjunctivitis (EAC). Allergic conjunctivitis was induced in mice by allergen challenge with ovalbumin in alum via the conjunctival sac. SOD3 was topically applied and allergy indicators were compared. Clinical signs associated with conjunctivitis, such as OVA-specific IgE production, IgG1/G2a ratio and eosinophil infiltration, were drastically reduced in mice treated with SOD3. They also had less dendritic cells and CD4+ T cells in conjunctiva than controls. Attenuated allergic inflammation was accredited to reduced Th2 type cytokine responses and increased Treg cytokine in draining lymph node. The characteristics of EAC were attributed to the absence of SOD3. Our findings suggest that SOD3 might be considered as a potential target for Th2-driven allergic conjunctival inflammation.
Extracellular superoxide dismutase (EC-SOD) is one of three mammalian SOD isozymes. Although there is knowledge of the functional role of EC-SOD in arteries, little is known about the function of EC-SOD in other tissues, including the brain. As a first step toward improving our understanding of EC-SOD in the brain, we studied the localization of EC-SOD in the central nervous system of the adult mouse using immunohistochemistry. We detected EC-SOD staining in a subpopulation of neurons throughout the brain as well as in tanycytes in the mediobasal hypothalamus. Particularly prominent EC-SOD staining was observed in neurons of the hilar region of the hippocampus, the lateral habenular nucleus of the thalamus, and the suprachiasmatic nuclei of the hypothalamus. Substantial numbers of neurons were distributed throughout the striatum and cortex; the morphology and distribution of these cells was similar to neurons previously shown to contain the neuronal isoform of nitric oxide synthase. In contrast to other regions with prominent EC-SOD immunoreactivity, EC-SOD localization in tanycytes occurred in a region lacking a blood-brain barrier. The high levels of EC-SOD present in discrete populations of cells in these regions suggest that EC-SOD plays an important, specialized role in the physiology and/or pathology in the brain.
Superoxide dismutases (SODs) are important enzymes in defence against oxidative stress. In Plasmodium falciparum, they may be expected to have special significance since part of the parasite life cycle is spent in red blood cells where the formation of reactive oxygen species is likely to be promoted by the products of haemoglobin breakdown. Thus, inhibitors of P. falciparum SODs have potential as anti-malarial compounds. As a step towards their development we have determined the crystal structure of the parasite's cytosolic iron superoxide dismutase.
Use of antioxidants to mitigate oxidative stress during ocular inflammatory diseases has shown therapeutic potential. This work examines a nanoscale therapeutic modality for the eye on the base of antioxidant enzyme, superoxide dismutase 1 (SOD1), termed "nanozyme." The nanozyme is produced by electrostatic coupling of the SOD1 with a cationic block copolymer, poly(L-lysine)-poly(ethyleneglycol), followed by covalent cross-linking of the complexes with 3,3'-dithiobis(sulfosuccinimidylpropionate) sodium salt. The ability of SOD1 nanozyme as well as the native SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with immunogenic uveitis. Results suggested that topical instillations of both enzyme forms demonstrated anti-inflammatory activity; however, the nanozyme was much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as the intensities of corneal and iris edema, hyperemia of conjunctiva, lens opacity, fibrin clots, and the protein content in aqueous humor. Clinical findings were confirmed by histological data. Thus, SOD1-containing nanozyme is potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.
Neuronal death following necrotic insults involves the generation of reactive oxygen species (ROS). We investigated the effects of antioxidant gene therapy on ROS accumulation after exposure to either sodium cyanide, kainic acid or oxygen glucose deprivation (OGD). Specifically, we generated herpes simplex virus-1 amplicon vector expressing the gene for the antioxidant enzyme CuZnSOD. Overexpression of this gene in primary hippocampal cultures resulted in increased enzymatic activity of the corresponding protein. CuZnSOD significantly protected hippocampal neurons against sodium cyanide insult and the subsequent lipid peroxidation. However, it did not protect against OGD- or kainic-acid-induced toxicity. Moreover, CuZnSOD significantly worsened the toxicity, hydrogen peroxide accumulation and lipid peroxidation induced by kainic acid. As a possible explanation for this surprising worsening, CuZnSOD overexpression increased glutathione peroxidase activity in the presence of sodium cyanide but had no effect on catalase or glutathione peroxidase activity in the presence of kainic acid. Thus, cells were unlikely to be able to detoxify the excess hydrogen peroxide produced as a result of the CuZnSOD overexpression. These studies can be viewed as a cautionary note concerning gene therapy intervention against necrotic insults.
Histochemical localization of superoxide anion (O2.-) scavenging activity in rat brain was visualized by the tissue-blotting technique. The activity was thought to mainly depend on Cu/Zn-SOD, because the localization of the activity was identical with the immunohistochemistry of Cu/Zn-SOD and the localization of its mRNA in the brain. Moreover, the activity was dramatically decreased after treatment of Cu (I) chelater. The activity was detected in pyramidal cells of the cortex, granular, and mitral cells of the olfactory bulbs, pyramidal cell layer CA1 to CA3, and dentate gyrus of hippocampus formation and granular cells of the cerebellum. Moreover, the activity was detected in the pontine nuclei of brain stem. Olfactory bulbs, hippocampus, and cerebellum were believed to be bestowed high brain functions, i.e., long-term potentiation and long-term depression. A part of the function was regulated by a retrograde neurotransmitter, nitric oxide (.NO). Our findings suggest that the SOD is colocalized with NO synthase in olfactory bulbs, hippocampus, and cerebellum, where .NO plays the important roles. In contrast, low SOD activity was observed in the axonal neurofiber bundles, although the regions contain a lot of membrane lipids, which was thought to be peroxidized by O2.- and related radicals such as .OH in the regions. From these findings, it was suggested that the SOD did not only play a role in protecting the neurons from endogenously formed O2.-, but also play a role in preservation of beneficial natures of .NO in the brain.
Superoxide dismutase (SOD) was modified into cationized form (Cat-SOD) in order to enhance its pharmacological efficacy based on an electrostatic interaction. The inhibitory effect of Cat-SOD on superoxide anion release from inflammatory macrophages and its cellular interaction were studied in vitro. Cat-SOD exhibited an excellent inhibitory effect on superoxide anion release from the macrophages, and this effect surpassed those of native SOD and SOD modified with mannose (Man-SOD) which is taken up via mannose receptor-mediated endocytosis by macrophages. In the presence of colchicine, a microtubule-disruptive agent, the inhibitory effect of Cat-SOD was slightly impaired, whereas the effect of Man-SOD completely disappeared. The intracellular localization of fluorescein isothiocyanate-labeled SOD, Cat-SOD and Man-SOD observed by confocal laser microscopy supported the difference in their abilities to eliminate superoxide anions. The different sensitivities of Cat-SOD and Man-SOD to colchicine were also confirmed by the confocal laser microscopic images, suggesting their distinct intracellular trafficking pathways in the macrophages. In conclusion, Cat-SOD is desirable for its pharmacological activity, which is probably the result of its ability to be delivered to the vicinity of NADPH-oxidase which locates in the cell membrane and generates superoxide anions.
Many Gram-negative bacteria interact with extracellular metal ions by expressing one or more siderophore types. Among these, the virulence-associated siderophore yersiniabactin (Ybt) is an avid copper chelator, forming stable cupric (Cu(II)-Ybt) complexes that are detectable in infected patients. Here we show that Ybt-expressing E. coli are protected from intracellular killing within copper-replete phagocytic cells. This survival advantage is highly dependent upon the phagocyte respiratory burst, during which superoxide is generated by the NADPH oxidase complex. Chemical fractionation links this phenotype to a previously unappreciated superoxide dismutase (SOD)-like activity of Cu(II)-Ybt. Unlike previously described synthetic copper-salicylate (Cu(II)-SA) SOD mimics, the salicylate-based natural product Cu(II)-Ybt retains catalytic activity at physiologically plausible protein concentrations. These results reveal a new virulence-associated adaptation based upon spontaneous assembly of a non-protein catalyst.
Oxidative stress is widely associated with disease and aging but the underlying mechanisms are incompletely understood. Here we show that the premature mortality of Drosophila deficient in superoxide scavengers, superoxide dismutase (SOD) 1 or SOD2, is rescued by chronic hypoxia. Strikingly, switching moribund SOD2-deficient adults from normoxia into hypoxia abruptly arrests their impending premature mortality and endows the survivors with a near-normal life span. This finding challenges the notion that irreversible oxidative damage initiated by unscavenged superoxide in the mitochondrial matrix underpins the premature mortality of SOD2-deficient adults. In contrast, switching moribund SOD1-deficient flies from normoxia into hypoxia fails to alter their mortality trajectory, suggesting that the deleterious effects of unscavenged superoxide in the cytoplasm/intermembrane space compartment are cumulative and largely irreversible. We conclude that cellular responses to superoxide-initiated oxidative stress are mediated through different compartment-specific pathways. Elucidating these pathways should provide novel insights into how aerobic cells manage oxidative stress in health, aging, and disease.
Welcome to the FDI Lab - SciCrunch.org Resources search. From here you can search through a compilation of resources used by FDI Lab - SciCrunch.org and see how data is organized within our community.
You are currently on the Community Resources tab looking through categories and sources that FDI Lab - SciCrunch.org has compiled. You can navigate through those categories from here or change to a different tab to execute your search through. Each tab gives a different perspective on data.
If you have an account on FDI Lab - SciCrunch.org then you can log in from here to get additional features in FDI Lab - SciCrunch.org such as Collections, Saved Searches, and managing Resources.
Here is the search term that is being executed, you can type in anything you want to search for. Some tips to help searching:
You can save any searches you perform for quick access to later from here.
We recognized your search term and included synonyms and inferred terms along side your term to help get the data you are looking for.
If you are logged into FDI Lab - SciCrunch.org you can add data records to your collections to create custom spreadsheets across multiple sources of data.
Here are the facets that you can filter your papers by.
From here we'll present any options for the literature, such as exporting your current results.
If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.
Year:
Count: