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European Review For Medical and... Apr 2021While both first-line antioxidant enzymes and oxidation products have been considered as markers of periodontal disease, their assessment in the diagnosis of periodontal...
OBJECTIVE
While both first-line antioxidant enzymes and oxidation products have been considered as markers of periodontal disease, their assessment in the diagnosis of periodontal disease is more complicated. Some, such as superoxide dismutase (SOD, glutathione peroxidase (GPx) and reduced glutathione (GSH), have indicated significant differences between patients with chronic and aggressive periodontitis.
PATIENTS AND METHODS
Participants (101) were divided into a control group of healthy individuals and, following diagnosis, patients with gingivitis, chronic periodontitis, and aggressive periodontitis. Compounds reflecting tissue destruction, inflammatory processes or antioxidant responses, such as sirtuins (SIRT-1, SIRT-2), metalloproteinases (MMP), SOD, GPx, GSH, and glutathione reductase (GR) were measured in saliva.
RESULTS
SIRT-2 levels were significantly increased in all patients. In patients with gingivitis, MMP (p<0.05) and GPx (p<0.01) were significantly increased. In patients with chronic and aggressive periodontitis, SOD activities were increased (p<0.001) while GPx and GR were decreased (p<0.001). Relative activities of MMP were higher in patients with aggressive periodontitis.
CONCLUSIONS
Measurements of SIRT-2 and SOD clearly showed increased levels of oxidative stress in cases of periodontitis with a subsequent inhibition of other antioxidant enzymes. Levels of GSH suggest reversibility of the conditions with appropriate intervention. With the assessment of the trends of these selected antioxidant markers, it is possible to determine the prognosis of the disease.
Topics: Biomarkers; Humans; Periodontitis; Prognosis; Saliva; Sirtuin 2; Superoxide Dismutase
PubMed: 33928601
DOI: 10.26355/eurrev_202104_25724 -
Materials Science & Engineering. C,... Sep 2020Cerium oxide nanoparticles (nanoceria) have recyclable antioxidative activity. It has numerous potential applications in biomedical engineering, such as mitigating...
Cerium oxide nanoparticles (nanoceria) have recyclable antioxidative activity. It has numerous potential applications in biomedical engineering, such as mitigating damage from burns, radiation, and bacterial infection. This mitigating activity is analogous to that property of metabolic enzymes such as superoxide dismutase (SOD) and catalase - scavengers of reactive oxygen species (ROS). Therefore, nanoceria can protect cells from environmental oxidative stress. This therapeutic effect prompted studies of nanoceria and metabolic enzymes as a combination therapy. The activity and structure of SOD, catalase, and lysozyme were examined in the presence of nanoceria. A complementary relationship between SOD and nanoceria motivated the present work, in which we explored a method for simultaneous delivery of SOD and nanoceria. The biocompatibility and tunable degradation of poly(lactic-co-glycolic acid) (PLGA) made it a candidate material for encapsulating both nanoceria and SOD. Cellular uptake studies were conducted along with a cytotoxicity assay. The antioxidative properties of PLGA-nanoceria-SOD particles were verified by adding HO to cell culture and imaging with fluorescent markers of oxidative stress. Our results suggest that PLGA is a suitable encapsulating carrier for simultaneous delivering nanoceria and SOD together, and that this combination effectively reduces oxidative stress in vitro.
Topics: Antioxidants; Catalase; Cerium; Hydrogen Peroxide; Nanoparticles; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase
PubMed: 32993995
DOI: 10.1016/j.msec.2020.111003 -
Journal of Inorganic Biochemistry Dec 2022A mononuclear Mn(III) complex of a clickable ligand, [Mn(hbpapn)(HO)]ClO·4.5HO, where Hhbpapn = 1,3-bis[(2-hydroxybenzyl)(propargyl)amino]propane, has been prepared...
A mononuclear Mn(III) complex of a clickable ligand, [Mn(hbpapn)(HO)]ClO·4.5HO, where Hhbpapn = 1,3-bis[(2-hydroxybenzyl)(propargyl)amino]propane, has been prepared and fully characterized. The complex catalyzes the dismutation of superoxide employing a Mn(III)/Mn(IV) redox cycle, with catalytic rate constant of 3.9 × 10 M s determined through the nitro blue tetrazolium photoreduction inhibition assay, in aqueous medium of pH 7.8. The alkyne function of the ligand was used for the covalent attachment of the catalyst to azide modified mesoporous silicas with different texture and morphology, through click chemistry. In these materials the catalyst is essentially linked to the inner pore walls, isolated and protected from the external medium. The hybrid materials can be recycled, and retain or improve the superoxide dismutase activity of the free catalyst with the pore size of the solid matrix playing a role on the activity of the catalyst.
Topics: Manganese; Ligands; Silicon Dioxide; Biomimetics; Superoxide Dismutase
PubMed: 36270893
DOI: 10.1016/j.jinorgbio.2022.112026 -
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 -
Acta Crystallographica. Section F,... Jul 2023Superoxide dismutase (SOD) is an essential and ubiquitous antioxidant protein that is widely present in biological systems. The anhydrobiotic tardigrades are some of the...
Superoxide dismutase (SOD) is an essential and ubiquitous antioxidant protein that is widely present in biological systems. The anhydrobiotic tardigrades are some of the toughest micro-animals. They have an expanded set of genes for antioxidant proteins such as SODs. These proteins are thought to play an essential role in oxidative stress resistance in critical situations such as desiccation, although their functions at the molecular level have yet to be explored. Here, crystal structures of a copper/zinc-containing SOD (RvSOD15) from an anhydrobiotic tardigrade, Ramazzottius varieornatus strain YOKOZUNA-1, are reported. In RvSOD15, one of the histidine ligands of the catalytic copper center is replaced by a valine (Val87). The crystal structures of the wild type and the V87H mutant show that even though a histidine is placed at position 87, a nearby flexible loop can destabilize the coordination of His87 to the Cu atom. Model structures of other RvSODs were investigated and it was found that some of them are also unusual SODs, with features such as deletion of the electrostatic loop or β3 sheet and unusual metal-binding residues. These studies show that RvSOD15 and some other RvSODs may have evolved to lose the SOD function, suggesting that gene duplications of antioxidant proteins do not solely explain the high stress tolerance of anhydrobiotic tardigrades.
Topics: Animals; Histidine; Antioxidants; Crystallography, X-Ray; Tardigrada; Superoxide Dismutase; Proteins
PubMed: 37358501
DOI: 10.1107/S2053230X2300523X -
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 -
Spectrochimica Acta. Part A, Molecular... May 2023Quinoline is a common nitrogen heterocyclic aromatic hydrocarbon with high water solubility. Studies have shown that quinoline can be teratogenic, carcinogenic and...
Quinoline is a common nitrogen heterocyclic aromatic hydrocarbon with high water solubility. Studies have shown that quinoline can be teratogenic, carcinogenic and mutagenic. And Hepatocytes are the target cell of quinoline, which contain a large number of mitochondria and are related to cell function and the balance of reactive oxygen species (ROS). However, the research on the effect of quinoline on hepatocyte damage and anti-oxidation system is still unclear. Through the means of multispectral experiments, it is concluded that quinoline can affect the catalase (CAT) and superoxide dismutase (SOD), change their structure and affect their activity. The binding mode and binding site of quinoline to CAT/SOD were analyzed by isothermal calorimetric titration (ITC) and Molecular Operating Environment (MOE). In molecular docking simulation, the binding site of quinoline-CAT system is close to the active site, and affect the microenvironment of Tyr 357. This may be the reason why quinoline affects CAT activity and synchronous fluorescence (Δλ = 15 nm). This study demonstrated that quinoline has a great effect on CAT, which may affect the intracellular ROS balance and become a potential way to cause hepatocyte damage.
Topics: Catalase; Reactive Oxygen Species; Molecular Docking Simulation; Superoxide Dismutase; Quinolines; Oxidative Stress
PubMed: 36753919
DOI: 10.1016/j.saa.2023.122449 -
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 -
The Journal of Physical Chemistry. B Jan 2020Recent studies have associated the absence of bound metals (Apo protein) and mutations in Cu-Zn Human Superoxide Dismutase (SOD1) with amyotrophic lateral sclerosis...
Recent studies have associated the absence of bound metals (Apo protein) and mutations in Cu-Zn Human Superoxide Dismutase (SOD1) with amyotrophic lateral sclerosis (ALS) disease, suggesting mechanisms of SOD1 aggregation. Using a structure-based model and modifying the energy of interaction between amino acids in the metal-binding site, we detected differences between the folding of the apo and holo proteins. The presence of metal ions decreases the free-energy barrier and also suggests that the folding pathway may change to reach the native state. The kinetics of folding of the apo and holo forms also correlates with the amount of free-energy barrier in the folding process. Also, the stability of the native state is significantly affected by the absence of metal ions. Our results, obtained from a very simplified model, correlate with more detailed studies, which also have shown that the transition and the native states are affected by the absence of the metal ions, hindering the folding of SOD1 and decreasing the stability of the native state. Regarding the disulfide bond, the results show that its absence decreases the stability of the native structure but affects the transition state less, suggesting that it is possibly made late in the folding process.
Topics: Humans; Kinetics; Models, Chemical; Mutation; Protein Folding; Superoxide Dismutase-1; Thermodynamics
PubMed: 31898906
DOI: 10.1021/acs.jpcb.9b09640