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Scientific Reports Apr 2023A novel hybrid protein composed of a superoxide dismutase-active Cu(II) complex (CuST) and lysozyme (CuST@lysozyme) was prepared. The results of the spectroscopic and...
A novel hybrid protein composed of a superoxide dismutase-active Cu(II) complex (CuST) and lysozyme (CuST@lysozyme) was prepared. The results of the spectroscopic and electrochemical analyses confirmed that CuST binds to lysozyme. We determined the crystal structure of CuST@lysozyme at 0.92 Å resolution, which revealed that the His15 imidazole group of lysozyme binds to the Cu(II) center of CuST in the equatorial position. In addition, CuST was fixed in position by the weak axial coordination of the Thr89 hydroxyl group and the hydrogen bond between the guanidinium group of the Arg14 residue and the hydroxyl group of CuST. Furthermore, the combination of CuST with lysozyme did not decrease the superoxide dismutase activity of CuST. Based on the spectral, electrochemical, structural studies, and quantum chemical calculations, an O disproportionation mechanism catalyzed by CuST@lysozyme is proposed.
Topics: Superoxide Dismutase; Superoxides; Oxidation-Reduction; Muramidase; Copper
PubMed: 37106030
DOI: 10.1038/s41598-023-33926-1 -
Nature Communications Apr 2021Human manganese superoxide dismutase is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers are used by the enzyme to...
Human manganese superoxide dismutase is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers are used by the enzyme to rid the mitochondria of O. The mechanisms of concerted transfer enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules at particular redox states. Here, neutron diffraction of two redox-controlled manganese superoxide dismutase crystals reveal the all-atom structures of Mn and Mn enzyme forms. The structures deliver direct data on protonation changes between oxidation states of the metal. Observations include glutamine deprotonation, the involvement of tyrosine and histidine with altered pKs, and four unusual strong-short hydrogen bonds, including a low barrier hydrogen bond. We report a concerted proton and electron transfer mechanism for human manganese superoxide dismutase from the direct visualization of active site protons in Mn and Mn redox states.
Topics: Amino Acids; Anions; Biocatalysis; Catalytic Domain; Electrons; Glutamine; Humans; Ligands; Neutrons; Protein Multimerization; Protons; Solvents; Superoxide Dismutase
PubMed: 33824320
DOI: 10.1038/s41467-021-22290-1 -
Nature Communications Aug 2021The ancestors of cyanobacteria generated Earth's first biogenic molecular oxygen, but how they dealt with oxidative stress remains unconstrained. Here we investigate...
The ancestors of cyanobacteria generated Earth's first biogenic molecular oxygen, but how they dealt with oxidative stress remains unconstrained. Here we investigate when superoxide dismutase enzymes (SODs) capable of removing superoxide free radicals evolved and estimate when Cyanobacteria originated. Our Bayesian molecular clocks, calibrated with microfossils, predict that stem Cyanobacteria arose 3300-3600 million years ago. Shortly afterwards, we find phylogenetic evidence that ancestral cyanobacteria used SODs with copper and zinc cofactors (CuZnSOD) during the Archaean. By the Paleoproterozoic, they became genetically capable of using iron, nickel, and manganese as cofactors (FeSOD, NiSOD, and MnSOD respectively). The evolution of NiSOD is particularly intriguing because it corresponds with cyanobacteria's invasion of the open ocean. Our analyses of metalloenzymes dealing with reactive oxygen species (ROS) now demonstrate that marine geochemical records alone may not predict patterns of metal usage by phototrophs from freshwater and terrestrial habitats.
Topics: Antioxidants; Bayes Theorem; Coenzymes; Copper; Cyanobacteria; Evolution, Molecular; Fresh Water; Iron; Manganese; Nickel; Oxidative Stress; Phylogeny; Reactive Oxygen Species; Superoxide Dismutase; Superoxides; Zinc
PubMed: 34362891
DOI: 10.1038/s41467-021-24396-y -
Brain, Behavior, and Immunity Oct 2022Neuroinflammation is one of the main hallmarks of amyotrophic lateral sclerosis (ALS). Recently, peripheral immune cells were discovered as pivotal players that promptly...
Neuroinflammation is one of the main hallmarks of amyotrophic lateral sclerosis (ALS). Recently, peripheral immune cells were discovered as pivotal players that promptly participate in this process, speeding up neurodegeneration during progression of the disease. In particular, infiltrating T cells and natural killer cells release inflammatory cytokines that switch glial cells toward a pro-inflammatory/detrimental phenotype, and directly attack motor neurons with specific ligand-receptor signals. Here, we assessed the presence of lymphocytes in the spinal cord of sporadic ALS patients. Furthermore, we demonstrate that blocking the extravasation of immune cells in the central nervous system using Natalizumab (NAT), an antibody for the α4 integrin, reduces the level of interferon-γ in the spinal cord of ALS mouse models, such as the hSOD1 and TDP43 mice, modifying microglia and astrocytes phenotype, increasing motor neuron number and prolonging the survival time. Taken together, our results establish a central role for the immune cells as drivers of inflammation in ALS.
Topics: Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Mice; Mice, Transgenic; Motor Neurons; Neuroinflammatory Diseases; Spinal Cord; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 35688338
DOI: 10.1016/j.bbi.2022.06.004 -
Microbes and Infection May 2023Infectious diseases cause redox imbalance and oxidative stress (OS) in host. Superoxide Dismutases(SOD) decrease this OS. SOD2 gene polymorphism can influence the...
BACKGROUND
Infectious diseases cause redox imbalance and oxidative stress (OS) in host. Superoxide Dismutases(SOD) decrease this OS. SOD2 gene polymorphism can influence the expression and levels of enzyme.
AIM
To investigate the association of genetic polymorphism of MnSOD with enzyme levels and mRNA expression in TB patients.
METHODS
A total of 87 TB patients and 85 healthy individuals participated in the study. The serum SOD2 levels were measured by ELISA. Gene polymorphism was analysed using PCR-RFLP with BsaW1 as the restriction enzyme. Expression was studied by Real-TimePCR. Statistical significance was determined using the Mann-Whitney, Chi-square and Kruskal-Wallis tests and p value < 0.05 was considered statistically significant.
RESULTS
The median(IQR) serum SOD2 levels of TB patients were lower than those of healthy subjects (4.64(6.48) vs 11.35(20.36)ng/mL respectively,p < 0.001). SOD2 expression was significantly down-regulated in TB patients with a fold change value of 0.312. The Val/Val genotype was higher in the patient group than healthy subjects (36.8% vs 23.5%). However, the difference observed between serum SOD2 levels and mRNA expression in the different genotypes were statistically non-significant.
CONCLUSION
Significant difference was found between levels and expression of SOD2 in TB patients and healthy controls, but not for SOD2 gene polymorphism.
Topics: Humans; India; Polymorphism, Genetic; Genotype; Superoxide Dismutase; Tuberculosis; Gene Expression; RNA, Messenger; Polymorphism, Single Nucleotide
PubMed: 36356830
DOI: 10.1016/j.micinf.2022.105075 -
Molecular Medicine Reports Mar 2016The antioxidant activities of superoxide dismutase 1 (SOD1) and SOD2, as well as the levels of the oxidant superoxide anion (SOA) and the micronutrients zinc (Zn),... (Comparative Study)
Comparative Study
The antioxidant activities of superoxide dismutase 1 (SOD1) and SOD2, as well as the levels of the oxidant superoxide anion (SOA) and the micronutrients zinc (Zn), copper (Cu) and manganese (Mn), were assayed in plasma, whole blood and placental tissue of non‑pregnant (NP), healthy pregnant (HP) women and recurrent miscarriage (RM) patients. The results showed that SOD1 and SOD2 activities and the levels of Zn, Cu and Mn in plasma and whole blood of HP women were slightly, but significantly lower, and even more significantly decreased in RM patients compared to those observed in NP women (P<0.05 and P<0.0001, respectively). Additionally, whereas plasma SOD1 and SOD2 activities and Zn, Cu and Mn levels were significantly lower in RM patients, those of whole blood and placental tissue were significantly lower when compared to HP women (P<0.001 and P<0.0001, respectively). Concurrently, there were consistent increases of equal magnitude and statistical significance in SOA levels in all the assayed samples as identified by a comparison between the subjects. The findings thus supported oxidative metabolism and excessive reactive oxygen species generation. The resultant oxidative stress, identified in whole blood and placental tissues of RM patients, may have been a primary cause of RM. Dietary supplementation of Zn, Cu and Mn may be beneficial to these patients pre- and post-conception.
Topics: Abortion, Habitual; Copper; Female; Gene Expression Profiling; Humans; Manganese; Placenta; Pregnancy; Reference Values; Saudi Arabia; Superoxide Dismutase; Superoxide Dismutase-1; Young Adult; Zinc
PubMed: 26821085
DOI: 10.3892/mmr.2016.4807 -
Research in Microbiology 2021The manganese superoxide dismutase (SodA) of E. faecium strain AUS0004 has been characterised. It is most closely related to Enterococcus hirae, Enterococcus durans,...
The manganese superoxide dismutase (SodA) of E. faecium strain AUS0004 has been characterised. It is most closely related to Enterococcus hirae, Enterococcus durans, Enterococcus villorium, and Enterococcus mundtii with 100%, 91,55%, 90,85%, and 90,58% homology, respectively, but more distant from SodA of E. faecalis (81.68%). A sodA deletion mutant has been constructed. Compared to the parental strain, the ΔsodA mutant was affected in aerobic growth and more sensitive to hydrogen peroxide (HO), cumene hydroperoxide (CuOOH), and the superoxide anion (O) generator menadione. The E. faecium strain AUS0004 is part of those bacteria accumulating HO to high concentrations (around 5 mM) starting from late exponential growth phase. Accumulation of the peroxide was around 25% less in the mutant suggesting that this part of HO is due to the dismutation of O by SodA. The sodA gene of E. faecium AUS0004 was induced by oxygen, peroxides and menadione but the corresponding regulator remains hitherto unknown. Finally, we showed that SodA activity is important for virulence in the Galleria mellonella model.
Topics: Aerobiosis; Animals; Antioxidants; Bacterial Proteins; Benzene Derivatives; Enterococcus faecium; Enzyme Induction; Genome, Bacterial; Hydrogen Peroxide; Moths; Oxidative Stress; Phylogeny; Superoxide Dismutase; Superoxides; Virulence
PubMed: 34474124
DOI: 10.1016/j.resmic.2021.103876 -
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 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Oct 2021To construct a hypobaric hypoxia-induced cell injury model. Rat pheochromocytoma PC12 cells were randomly divided into control group, normobaric hypoxia group and...
To construct a hypobaric hypoxia-induced cell injury model. Rat pheochromocytoma PC12 cells were randomly divided into control group, normobaric hypoxia group and hypobaric hypoxia group. The cells in control group were cultured at normal condition, while cells in other two groups were cultured in normobaric hypoxia and hypobaric hypoxia conditions, respectively. CCK-8 method was used to detect cell viability to determine the optimal modeling conditions like the oxygen concentration, atmospheric pressure and low-pressure hypoxia time. The contents of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by microplate method. The apoptosis ratio and cell cycle were analyzed by flow cytometry. The hypobaric hypoxia-induced cell injury model can be established by culturing for 24 h at 1% oxygen concentration and 41 kPa atmospheric pressure. Compared with the control group and normobaric hypoxia group, the activity of LDH and the content of MDA in hypobaric hypoxia group were significantly increased, the activity of SOD was decreased, the percentage of apoptosis was increased (all <0.05), and the cell cycle was arrested in G0/G1 phase. A stable and reliable cell injury model induced by hypobaric hypoxia has been established with PC12 cells, which provides a suitable cell model for the experimental study on nerve injury induced by hypoxia at high altitude.
Topics: Animals; Cell Hypoxia; Hypoxia; Malondialdehyde; PC12 Cells; Rats; Superoxide Dismutase
PubMed: 34986528
DOI: 10.3724/zdxbyxb-2021-0343 -
Biomedicine & Pharmacotherapy =... May 2021The alterations in concentration/activity of superoxide dismutase isozymes in the context of type 2 diabetes or obesity are well-described. Moreover, many hereditary...
Concentration/activity of superoxide dismutase isozymes and the pro-/antioxidative status, in context of type 2 diabetes and selected single nucleotide polymorphisms (genes: INS, SOD1, SOD2, SOD3) - Preliminary findings.
The alterations in concentration/activity of superoxide dismutase isozymes in the context of type 2 diabetes or obesity are well-described. Moreover, many hereditary factors, including single-nucleotide polymorphisms (SNPs) of genes for coding insulin, insulin receptors, or insulin receptor substrates (INS, INSR, IRS1, IRS2) or superoxide dismutase isozymes (SOD1, SOD2, SOD3), have been linked with the incidence of obesity and diabetes. However, the underlying changes in the plasma concentration/activity of superoxide dismutase isozymes and their potential connection with the said hereditary factors remain unexplored. Previously, we have observed that the plasma concentration/activity of superoxide dismutase isozymes differs in the context of obesity and/or rs2234694 (SOD1) and rs4880 (SOD2) and that the concentrations of SOD1, SOD2, SOD3 are correlated with each other. Intersexual variability of SOD1 concentration was detected regardless of obesity. In this study, the variability of concentration/activity of superoxide dismutase isozymes in plasma is considered in the context of type 2 diabetes and/or SNPs: rs2234694 (SOD1), rs5746105 (SOD2), rs4880 (SOD2), rs927450 (SOD2), rs8192287 (SOD3). Genotypic variability of SNP rs3842729 (INS), previously studied in the context of insulin-dependent diabetes, is investigated in terms of selected clinical parameters associated with type 2 diabetes. This study revealed higher SOD1 concentration in diabetic men compared to women, and extremely high SOD1 concentration, higher total superoxide dismutase, and copper-zinc superoxide dismutase activity, and lower superoxide dismutase and copper-zinc superoxide dismutase activity (when adjusted for the concentration of SODs) in the diabetic group regardless of sex. Multiple logistic regression, applied to explore possible links between the studied SNPs and other factors with the odds of type 2 diabetes or obesity, revealed that the genotypic variability of rs4880 (SOD2) could affect these odds, supporting the findings of several other studies.
Topics: Adult; Aged; Antioxidants; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Genotype; Humans; Insulin; Isoenzymes; Male; Metals; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Sex Characteristics; Smoking; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 33761612
DOI: 10.1016/j.biopha.2021.111396