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Journal of Neurology, Neurosurgery, and... Feb 2022
Topics: Amyotrophic Lateral Sclerosis; Humans; Mutation; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 34599043
DOI: 10.1136/jnnp-2021-327935 -
Nutrition (Burbank, Los Angeles County,... Mar 2015Dietary antioxidant supplementation has been popular in Western countries. Various supplements have been developed in recent years, and research has been gathered from... (Review)
Review
Dietary antioxidant supplementation has been popular in Western countries. Various supplements have been developed in recent years, and research has been gathered from both animal and clinical research trials. In this review, the therapeutic value of oral administration of a combination of melon superoxide dismutase (SOD) and a vegetable polymer (gliadin) is evaluated. Critical examination of the effects of SOD-gliadin supplementation is carried out, with an emphasis on its impact on oxidative stress levels and on endogenous antioxidant pathways. Overall analysis of peer-reviewed published data suggests that intake of SOD-gliadin might have advantageous health effects. These conclusions are dependent on the condition or pathology under consideration. In general, the authors, who analyzed SOD-gliadin supplementation, support the use of SOD-gliadin supplementation as a complementary treatment rather than a therapeutic treatment. To further clarify the importance of dietary SOD-gliadin administration, additional large-scale clinical trials are recommended.
Topics: Antioxidants; Cucumis melo; Cucurbitaceae; Dietary Supplements; Gliadin; Humans; Oxidative Stress; Phytotherapy; Plant Extracts; Superoxide Dismutase; Triticum
PubMed: 25701330
DOI: 10.1016/j.nut.2014.10.006 -
Journal of Evolutionary Biology Jul 2021Cetacea, whales, dolphins and porpoises form an order of mammals adapted to aquatic life. Their transition to an aquatic habitat resulted in exceptional protection...
Cetacea, whales, dolphins and porpoises form an order of mammals adapted to aquatic life. Their transition to an aquatic habitat resulted in exceptional protection against cellular insults, including oxidative and osmotic stress. Here, we considered the structure and molecular evolution of the superoxide dismutase (SOD) gene family, which encodes essential enzymes in the mammalian antioxidant system, in the superorder Cetartiodactyla. To this end, we juxtaposed cetaceans and their closest extant relatives (order Artiodactyla). We identified 94 genes in 23 species, of which 70 are bona fide intact genes. Although the SOD gene family is conserved in Cetartiodactyla, lineage-specific gene duplications and deletions were observed. Phylogenetic analyses show that the SOD2 subfamily diverged from a clade containing SOD1 and SOD3, suggesting that cytoplasmic, extracellular and mitochondrial SODs have started down independent evolutionary paths. Specific-amino acid changes (e.g. K130N in SOD2) that may enhance ROS elimination were identified in cetaceans. In silico analysis suggests that the core transcription factor repertoire of cetartiodactyl SOD genes may include Sp1, NF-κB, Nrf2 and AHR. Putative transcription factors binding sites responding to hypoxia were (e.g. Suppressor of Hairless; Su(H)) found in the cetacean SOD1 gene. We found significant evidence for positive selection in cetaceans using codon models. Cetaceans with different diving abilities also show divergent evolution of SOD1 and SOD2. Our genome-wide analysis of SOD genes helps clarify their relationship and evolutionary trajectory and identify putative functional changes in cetaceans.
Topics: Animals; Artiodactyla; Cetacea; Mammals; Phylogeny; Superoxide Dismutase
PubMed: 33896059
DOI: 10.1111/jeb.13792 -
Science Advances Nov 2023Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone-collapsing factor. Previous reports have demonstrated the multifunctional roles...
Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone-collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients with ALS and transgenic mice overexpressing the mutant human superoxide dismutase1 (mSOD1 mice). Treatment with humanized anti-RGMa monoclonal antibody ameliorated the clinical symptoms in mSOD1 mice. Histochemical analysis revealed that the anti-RGMa antibody significantly decreased mutant SOD1 protein accumulation in the motor neurons of mSOD1 mice via inhibition of actin depolymerization. In vitro analysis revealed that the anti-RGMa antibody inhibited the cellular uptake of the mutant SOD1 protein, presumably by reinforcing the neuronal actin barrier. Collectively, these data suggest that RGMa leads to the collapse of the neuronal actin barrier and promotes aberrant protein deposition, resulting in exacerbation of the ALS pathology.
Topics: Animals; Humans; Mice; Actins; Amyotrophic Lateral Sclerosis; Antibodies; Mice, Transgenic; Motor Neurons; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 37992159
DOI: 10.1126/sciadv.adg3193 -
PloS One 2022To identify the effects of superoxide dismutase (SOD)3 on diabetes mellitus (DM)-induced retinal changes in a diabetic rat model.
PURPOSE
To identify the effects of superoxide dismutase (SOD)3 on diabetes mellitus (DM)-induced retinal changes in a diabetic rat model.
METHODS
Diabetic models were established by a single intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. After purification of the recombinant SOD3, intravitreal injection of SOD3 was performed at the time of STZ injection, and 1 and 2 weeks following STZ injection. Scotopic and photopic electroretinography (ERG) were recorded. Immunofluorescence staining with ɑ-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), pigment epithelium-derived factor (PEDF), Flt1, recoverin, parvalbumin, extracellular superoxide dismutase (SOD3), 8-Hydroxy-2'deoxyguanosine (8-OHdG) and tumor necrosis factor-ɑ (TNF-ɑ) were evaluated.
RESULTS
In the scotopic ERG, the diabetic group showed reduced a- and b-wave amplitudes compared with the control group. In the photopic ERG, b-wave amplitude showed significant (p < 0.0005) reduction at 8 weeks following DM induction. However, the trend of a- and b-wave reduction was not evident in the SOD3 treated group. GFAP, Flt1, 8-OHdG and TNF-ɑ immunoreactivity were increased, and ɑ-SMA, PEDF and SOD3 immunoreactivity were decreased in the diabetic retina. The immunoreactivity of these markers was partially recovered in the SOD3 treated group. Parvalbumin expression was not decreased in the SOD3 treated group. In the diabetic retinas, the immunoreactivity of recoverin was weakly detected in both of the inner nuclear layer and inner plexiform layer compared to the control group but not in the SOD3 treated group.
CONCLUSIONS
SOD3 treatment attenuated the loss of a/b-wave amplitudes in the diabetic rats, which was consistent with the immunohistochemical evaluation. We also suggest that in rod-dominant rodents, the use of blue on green photopic negative response (PhNR) is effective in measuring the inner retinal function in animal models of diabetic retinopathy. SOD3 treatment ameliorated the retinal Müller cell activation in diabetic rats and pericyte dysfunction. These results suggested that SOD3 exerted protective effects on the development of diabetic retinopathy.
Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Intravitreal Injections; Male; Rats; Rats, Sprague-Dawley; Superoxide Dismutase
PubMed: 35015779
DOI: 10.1371/journal.pone.0262396 -
Journal of Structural Biology Jul 2017Superoxide dismutases (SODs) are enzymes that play a key role in protecting cells from toxic oxygen metabolites by disproportionation of two molecules of superoxide into...
Superoxide dismutases (SODs) are enzymes that play a key role in protecting cells from toxic oxygen metabolites by disproportionation of two molecules of superoxide into molecular oxygen and hydrogen peroxide via cyclic reduction and oxidation at the active site metal. The azide anion is a potent competitive inhibitor that binds directly to the metal and is used as a substrate analog to superoxide in studies of SOD. The crystal structure of human MnSOD-azide complex was solved and shows the putative binding position of superoxide, providing a model for binding to the active site. Azide is bound end-on at the sixth coordinate position of the manganese ion. Tetrameric electrostatic surfaces were calculated incorporating accurate partial charges for the active site in three states, including a state with superoxide coordinated to the metal using the position of azide as a model. These show facilitation of the anionic ligand to the active site pit via a 'valley' of positively-charged surface patches. Surrounding ridges of negative charge help guide the superoxide anion. Within the active site pit, Arg173 and Glu162 further guide and align superoxide for efficient catalysis. Superoxide coordination at the sixth position causes the electrostatic surface of the active site pit to become nearly neutral. A model for electrostatic-mediated diffusion, and efficient binding of superoxide for catalysis is presented.
Topics: Azides; Binding Sites; Catalysis; Humans; Models, Molecular; Static Electricity; Substrate Specificity; Superoxide Dismutase
PubMed: 28461152
DOI: 10.1016/j.jsb.2017.04.011 -
Molecules (Basel, Switzerland) Apr 2022This study aimed to elucidate the responses of a novel characterized WJL-G4 against citric acid stress by performing physiological analysis, morphology observation, and...
This study aimed to elucidate the responses of a novel characterized WJL-G4 against citric acid stress by performing physiological analysis, morphology observation, and structural and membrane fatty acid composition analysis. The results showed that under citric acid stress, the cell vitality of WJL-G4 was reduced. The cell morphology changed with the unclear, uncompleted and thinner cell wall, and degraded the cell structure. When the citric acid concentration was 20 g/L, WJL-G4 could tolerate citric acid and maintain the cell structure by increasing the intracellular pH, superoxide dismutase activity, and contents of unsaturated fatty acids. As the citric acid concentration was ≥80 g/L, the stress has exceeded the cellular anti-stress ability, causing substantial cell damage. The cell membrane permeability, the content of membrane lipids, malondialdehyde and superoxide anion increased, but the intracellular pH and superoxide dismutase activities decreased, accompanying the increase of citric acid concentrations. The findings of this work provided a theoretical basis for the responsive mechanism of WJL-G4 under high concentrations of citric acid, and can serve as a reference for biological acid reduction in fruit processing.
Topics: Acids; Citric Acid; Malondialdehyde; Pichia; Superoxide Dismutase
PubMed: 35566015
DOI: 10.3390/molecules27092664 -
Neurobiology of Disease Aug 2023The progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS) is caused by a decline in motor neuron function, resulting in worsened motor impairments,...
The progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS) is caused by a decline in motor neuron function, resulting in worsened motor impairments, malnutrition, respiratory failure and mortality, and there is a lack of effective clinical treatments. The exact mechanism of motor neuronal degeneration remains unclear. Previously, we reported that ferroptosis, which is characterized by the accumulation of lipid peroxide and glutathione depletion in an iron-dependent manner, contributed to motor neuronal death in ALS cell models with the hSOD1 (human Cu/Zn-superoxide dismutase) gene mutation. In this study, we further explored the role of ferroptosis in motor neurons and its regulation in mutant hSOD1 cell and mouse models. Our results showed that ferroptosis was activated in hSOD1 NSC-34 cells and mouse models, which was accompanied by decreased nuclear retention of nuclear factor erythroid 2-related factor 2 (NRF2) and downregulation of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) levels. Moreover, RTA-408, an NRF2 activator, inhibited ferroptosis in hSOD1 NSC-34 cells by upregulating the protein expression of SLC7A11 and GPX4. Moreover, hSOD1 mice treated with RTA-408 showed obvious improvements in body weight and motor function. Our study demonstrated that ferroptosis contributed to the toxicity of motor neurons and that activating NRF2 could alleviate neuronal degeneration in ALS with the hSOD1 mutation.
Topics: Animals; Humans; Mice; Amyotrophic Lateral Sclerosis; Disease Models, Animal; Ferroptosis; Mice, Transgenic; Motor Neurons; Mutation; Neurodegenerative Diseases; Neuroprotection; NF-E2-Related Factor 2; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 37352984
DOI: 10.1016/j.nbd.2023.106210 -
Journal of Nanobiotechnology May 2024Various clinical symptoms of digestive system, such as infectious, inflammatory, and malignant disorders, have a profound impact on the quality of life and overall... (Review)
Review
Various clinical symptoms of digestive system, such as infectious, inflammatory, and malignant disorders, have a profound impact on the quality of life and overall health of patients. Therefore, the chase for more potent medicines is both highly significant and urgent. Nanozymes, a novel class of nanomaterials, amalgamate the biological properties of nanomaterials with the catalytic activity of enzymes, and have been engineered for various biomedical applications, including complex gastrointestinal diseases (GI). Particularly, because of their distinctive metal coordination structure and ability to maximize atom use efficiency, single-atom nanozymes (SAzymes) with atomically scattered metal centers are becoming a more viable substitute for natural enzymes. Traditional nanozyme design strategies are no longer able to meet the current requirements for efficient and diverse SAzymes design due to the diversification and complexity of preparation processes. As a result, this review emphasizes the design concept and the synthesis strategy of SAzymes, and corresponding bioenzyme-like activities, such as superoxide dismutase (SOD), peroxidase (POD), oxidase (OXD), catalase (CAT), and glutathione peroxidase (GPx). Then the various application of SAzymes in GI illnesses are summarized, which should encourage further research into nanozymes to achieve better application characteristics.
Topics: Humans; Gastrointestinal Diseases; Nanostructures; Animals; Enzymes; Superoxide Dismutase; Catalase; Catalysis; Glutathione Peroxidase
PubMed: 38796465
DOI: 10.1186/s12951-024-02569-3 -
International Journal of Molecular... Jun 2021Quantum dots (QDs) have a broad range of applications in cell biolabeling, cancer treatment, metastasis imaging, and therapeutic drug monitoring. Despite their wide use,...
Quantum dots (QDs) have a broad range of applications in cell biolabeling, cancer treatment, metastasis imaging, and therapeutic drug monitoring. Despite their wide use, relatively little is known about their influence on other molecules. Interactions between QDs and proteins can influence the properties of both nanoparticles and proteins. The effect of mercaptosuccinic acid-capped CdTe QDs on intercellular copper-zinc superoxide dismutase (SOD1)-one of the main enzymatic antioxidants-was investigated. Incubation of SOD1 with QDs caused an increase in SOD1 activity, unlike in the case of CdCl, which inhibited SOD1. Moreover, this effect on SOD1 increased with the size and potential of QDs, although the effect became clearly visible in higher concentrations of QDs. The intensity of QD-SOD1 fluorescence, analyzed with the use of capillary electrophoresis with laser-induced fluorescence detection, was dependent on SOD1 concentration. In the case of green QDs, the fluorescence signal decreased with increasing SOD1 concentration. In contrast, the signal strength for Y-QD complexes was not dependent on SOD1 dilutions. The migration time of QDs and their complexes with SOD1 varied depending on the type of QD used. The migration time of G-QD complexes with SOD1 differed slightly. However, in the case of Y-QD complexes with SOD1, the differences in the migration time were not dependent on SOD concentration. This research shows that QDs interact with SOD1 and the influence of QDs on SOD activity is size-dependent. With this knowledge, one might be able to control the activation/inhibition of specific enzymes, such as SOD1.
Topics: Cadmium Compounds; Electrophoresis, Capillary; Fluorescence; Humans; Nanoparticles; Quantum Dots; Spectrometry, Fluorescence; Superoxide Dismutase; Tellurium
PubMed: 34200401
DOI: 10.3390/ijms22116156