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Bioscience Reports Jun 2022In this review, we focus on understanding the structure-function relationships of numerous manganese superoxide dismutase (MnSOD) mutants to investigate the role that... (Review)
Review
In this review, we focus on understanding the structure-function relationships of numerous manganese superoxide dismutase (MnSOD) mutants to investigate the role that various amino acids play to maintain enzyme quaternary structure or the active site structure, catalytic potential and metal homeostasis in MnSOD, which is essential to maintain enzyme activity. We also observe how polymorphisms of MnSOD are linked to pathologies and how post-translational modifications affect the antioxidant properties of MnSOD. Understanding how modified forms of MnSOD may act as tumor promoters or suppressors by altering the redox status in the body, ultimately aid in generating novel therapies that exploit the therapeutic potential of mutant MnSODs or pave the way for the development of synthetic SOD mimics.
Topics: Catalysis; Catalytic Domain; Structure-Activity Relationship; Superoxide Dismutase
PubMed: 35662317
DOI: 10.1042/BSR20220202 -
Journal of the College of Physicians... Jul 2021To compare superoxide dismutase 1 (SOD1) levels in diabetes mellitus patients with and without neuropathy.
OBJECTIVE
To compare superoxide dismutase 1 (SOD1) levels in diabetes mellitus patients with and without neuropathy.
STUDY DESIGN
Cross-sectional comparative study.
PLACE AND DURATION OF STUDY
Multidisciplinary Lab-1 of the Department of Biochemistry and Molecular Biology, Army Medical College, in cooperation with Pak-Emirates Military Hospital, Rawalpindi, Pakistan, from January 2020 to January 2021.
METHODOLOGY
Eighty-four subjects were enrolled through non-probability purposive sampling technique. They were further divided into three groups. Patients with diabetic neuropathy were labelled as the group Ι, and patients with diabetes mellitus without neuropathy were included in group ΙΙ. While group ΙΙΙ was comprised of healthy individuals and taken as control. Biochemical parameters included fasting blood glucose levels and HbA1c. Superoxide dismutase-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Data were evaluated by SPSS version 22.0 and presented in percentage and mean ± standard deviation (SD). Independent sample t-test and one-way ANOVA followed by the post-hoc Tukey test were used for group comparison.
RESULTS
Mean level of SOD1 was significantly higher in group Ι as compared to group ΙΙ and ΙΙΙ (p<0.001). Statistically significant difference was observed among groups Ι and ΙΙ (p=0.002), Ι and ΙΙΙ (p<0.001), and ΙΙ and ΙΙΙ (p=0.017). Mean levels of SOD1 were also significantly increased with poor glycemic control (p<0.001).
CONCLUSION
SOD1 level was considerably high in patients with diabetes mellitus with neuropathy in comparison to diabetics without neuropathy and healthy individuals. Key Words: Diabetes mellitus, Diabetic neuropathy, ELISA, Superoxide dismutase 1(SOD1).
Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Pakistan; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 34271773
DOI: 10.29271/jcpsp.2021.07.765 -
Biotechnology Letters Jan 2023We aimed to clone and express the human Cu, Zn superoxide dismutase (hSOD1) in Bacillus subtilis 1012. Also, we investigated the expression level of hSOD1 under...
OBJECTIVE
We aimed to clone and express the human Cu, Zn superoxide dismutase (hSOD1) in Bacillus subtilis 1012. Also, we investigated the expression level of hSOD1 under different induction conditions.
RESULT
As an essential member of the antioxidant defense system in vivo, hSOD1 has become a therapeutic agent against host diseases, such as oxygen toxicity, acute inflammation, and radiation injury. The recombinant hSOD1 was successfully secreted extracellularly into B. subtilis 1012. The expression conditions were optimized, including inoculum size, different media, temperatures, and inducer concentrations. Finally, the highest level of hSOD1 was produced as a soluble form in Super rich medium by 2% inoculum with 0.2 mM of IPTG at 37 °C after the induction for 24 h. Besides, 20 g/L of lactose also displayed the same inductive effect on hSOD1 expression as that of IPTG (0.2 mM). Finally, the specific activity of purified hSOD1 was determined to be 1625 U/mg in the presence of 800 μM of Cu and 20 μM of Zn.
CONCLUSIONS
We propose that the B. subtilis 1012-hSOD1 strain system has great potential in future industrial applications.
Topics: Humans; Bacillus subtilis; Cloning, Molecular; Isopropyl Thiogalactoside; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 36469194
DOI: 10.1007/s10529-022-03319-x -
Archives of Physiology and Biochemistry Oct 2020Superoxide dismutase (SOD) enzymes are considered the first line of Defence against reactive oxygen species. Among the intracellular isoforms of SOD, Cu,ZnSOD is widely...
Superoxide dismutase (SOD) enzymes are considered the first line of Defence against reactive oxygen species. Among the intracellular isoforms of SOD, Cu,ZnSOD is widely distributed, and the MnSOD is localised in the mitochondria. The SOD activities have been measured indirectly by inhibiting oxidation reactions. Most techniques assessing the hepatic SOD activity are adaptations of classical methods and differ significantly from each other. This work assessed the hepatic Cu,ZnSOD activity in the supernatants of two different centrifugations, using two isotonic medium and the pyrogallol method. In most studies conducted in rat liver, only the Cu,Zn or total SOD activities were assessed and sometimes the Cu,ZnSOD activity was calculated based on the inhibition by cyanide. But, as demonstrated here, this inhibition is not complete. Besides, the novelty of this work is that we presented a method for the evaluating the Cu,ZnSOD and MnSOD activities separately and from the same liver.
Topics: Animals; Enzyme Assays; Liver; Rats; Superoxide Dismutase
PubMed: 30372625
DOI: 10.1080/13813455.2018.1520891 -
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 -
International Journal of Biological... Sep 2021Superoxide dismutases (SODs) (EC 1.15.1.1) are well known antioxidant enzymes that play critical roles in cellular defenses of living organisms against harmful...
Superoxide dismutases (SODs) (EC 1.15.1.1) are well known antioxidant enzymes that play critical roles in cellular defenses of living organisms against harmful superoxide radicals during oxidative stress. This study details on cloning, biochemical and functional characterization of an iron containing type superoxide dismutase (SOD) from a novel thermophilic bacteria Cohnella sp. A01 (CaSOD). The secondary and three dimensional structure of the protein were predicted. CaSOD gene was subsequently cloned into pET-26b(+) expression vector and expression of the recombinant protein (rCaSOD) was optimized in E. coli BL21 (DE3) and the purified recombinant SOD showed a single band with an apparent molecular weight of 26 kDa by SDS-PAGE. The half-life and thermodynamic parameters including ΔH, ΔS, and ΔG were 187 min at 60 °C, 7.3 kJ.mol, -76.8 kJ.mol.°K, and 84.1 kJ.mol, respectively. The rCaSOD exhibited catalytic activity in a very broad range of pH (6.0-10.0) and temperatures (35-75 °C), as well as stability in a broad pH range, from 3.0 to 11.0, and wide range of temperature, different concentrations of detergent agents, metal ions, organic solvents and other chemicals. The results suggest that this novel enzyme could be used for various industrial applications in cosmetic, food, and pharmaceutical industries.
Topics: Amino Acid Sequence; Bacillales; Bacterial Proteins; Catalysis; Cloning, Molecular; Enzyme Stability; Hydrogen Peroxide; Hydrogen-Ion Concentration; Iron; Protein Conformation; Structure-Activity Relationship; Substrate Specificity; Superoxide Dismutase; Superoxides; Temperature
PubMed: 34329665
DOI: 10.1016/j.ijbiomac.2021.07.150 -
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 -
Development, Growth & Differentiation Dec 2020Dictyostelium cells cope with hypo-osmotic stress with a contractile vacuole (CV) system, which consists of one or two vacuoles that cyclically charge and discharge....
Dictyostelium cells cope with hypo-osmotic stress with a contractile vacuole (CV) system, which consists of one or two vacuoles that cyclically charge and discharge. Uniquely, a F-Actin remodeling dependent minimal mixing of the CV membrane components with the target plasmalemma during the fusion and the dischargement warrants the integrity of the CV bladder for an efficient next CV cycle. The effect of hypo-osmotic stress on F-Actin remodeling activity, however, is currently not well understood. Dictyostelium cells increase the level of intracellular superoxide level in response to hypo-osmotic stress, which in turn activates redox-sensitive Ras proteins, but not Akt, which is one of the Ras downstream targets and a major regulator of F-Actin remodeling. However, Akt is not insulated from the active Ras in cells lacking Superoxide dismutase C (SodC). We report here that sodC cells were compromised in the CV structure and function and the attenuation of Ras/PI3K/Akt signaling in several independent means significantly improved the compromised CV structure but not the function. Interestingly, when sodC cells were treated with 5-(N,N-Dimethyl) amiloride hydrochloride (EIPA), an inhibitor of sodium proton exchanger (NHE), both the structure and the function of the CV improved. Thus, a proper CV biogenesis in sodC cells was insufficient to restore their CV function, which in turn indicates the presence of an additional target for SodC and EIPA that modulates CV function.
Topics: Cells, Cultured; Dictyostelium; Superoxide Dismutase; Vacuoles
PubMed: 33118157
DOI: 10.1111/dgd.12698 -
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 -
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