-
Medical Science Monitor : International... Mar 2019BACKGROUND This systematic review of the literature and meta-analysis aimed to review the evaluation and monitoring of superoxide dismutase (SOD) activity and its... (Meta-Analysis)
Meta-Analysis
BACKGROUND This systematic review of the literature and meta-analysis aimed to review the evaluation and monitoring of superoxide dismutase (SOD) activity and its clinical significance in gastric cancer. MATERIAL AND METHODS Systematic review involved searching the PubMed, Embase, Ovid, and the China National Knowledge Infrastructure (CNKI) databases. Search terms included 'superoxide dismutase,' and 'gastric cancer.' Studies that included measurements of SOD activity in peripheral blood samples in patients with SOD activity compared with healthy controls. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS Ten controlled clinical studies were identified that included six studies that measured SOD in serum, three in erythrocytes, and one study that measured SOD on whole blood. Meta-analysis, using the standardized mean difference (SMD) and the 95% confidence interval (CI), showed that patients with gastric cancer had significantly decreased SOD activity when compared with the healthy controls (SMD, -0.840; 95% CI, -1.463 to -0.218; p=0.008). Subgroup analysis was conducted on SOD distribution in the blood (erythrocyte: SMD, -1.773; 95% CI, -2.504 to -1.042; p=0.000) (serum SMD, -0.322; 95% CI, -1.006-0.361; p=0.355) (whole blood: SMD, -1.251; 95% CI, -1.731 to -0.771; p=0.000) and for male subjects (SMD, -2.090; 95% CI, -2.725 to -1.456; p<0.001). CONCLUSIONS Meta-analysis showed that SOD measurements from blood samples, especially in erythrocytes, had potential as a diagnostic and monitoring parameter in patients with gastric cancer.
Topics: Biomarkers, Tumor; Female; Humans; Male; Stomach Neoplasms; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 30886134
DOI: 10.12659/MSM.913375 -
Journal of Aerosol Medicine and... Oct 2023Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of...
Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of alveolar-capillary membranes, pulmonary edema, and acute onset hypoxemia. During the ARDS acute phase, neutrophil infiltration into the alveolar space results in uncontrolled release of reactive oxygen species (ROS) and proteases, overwhelming antioxidant defenses and causing alveolar epithelial and lung endothelial injury. To investigate the therapeutic potential of a novel recombinant human Cu-Zn-superoxide dismutase (SOD) fusion protein in protecting against ROS injury and for aerosolized SOD delivery to treat induced ARDS. Fusion proteins incorporating human Cu-Zn-SOD (hSOD1), with (pep1-hSOD1-his) and without (hSOD1-his) a fused hyaluronic acid-binding peptide, were expressed in . Purified proteins were evaluated in assays with human bronchial epithelial cells and through aerosolized delivery to the lung of an -induced ARDS rat model. SOD proteins exhibited high SOD activity and protected bronchial epithelial cells from oxidative damage. hSOD1-his and pep1-hSOD1-his retained SOD activity postnebulization and exhibited no adverse effects in the rat. Pep1-hSOD1-his administered through instillation or nebulization to the lung of an -induced pneumonia rat improved arterial oxygenation and lactate levels compared to vehicle after 48 hours. Static lung compliance was improved when the pep1-hSOD1-his protein was delivered by instillation. White cell infiltration to the lung was significantly reduced by aerosolized delivery of protein, and reduction of cytokine-induced neutrophil chemoattractant-1, interferon-gamma, and interleukin 6 pro-inflammatory cytokine concentrations in bronchoalveolar lavage was observed. Aerosol delivery of a novel recombinant modified SOD protein reduces oxidant injury and attenuates induced lung injury in rats. The results provide a strong basis for further investigation of the therapeutic potential of hSOD1 in the treatment of ARDS.
Topics: Rats; Humans; Animals; Lung Injury; Escherichia coli; Reactive Oxygen Species; Oxidants; Administration, Inhalation; Respiratory Aerosols and Droplets; Superoxide Dismutase; Lung; Respiratory Distress Syndrome; Pneumonia, Bacterial; Cytokines
PubMed: 37638822
DOI: 10.1089/jamp.2022.0069 -
International Journal of Biological... Jan 2021The overproduction of free radicals can cause oxidative-stress damage to a range of biomolecules, and thus potentially contribute to several pathologies, from... (Review)
Review
The overproduction of free radicals can cause oxidative-stress damage to a range of biomolecules, and thus potentially contribute to several pathologies, from neurodegenerative disorders to cardiovascular diseases and metabolic disorders. Endogenous antioxidant enzymes, such as superoxide dismutase (SOD), play an important role in diminishing oxidative stress. SOD supplementation could therefore be an effective preventive strategy to reduce the risk of free-radical overproduction. However, the efficacy of SOD administration is hampered by its rapid clearance. Several different approaches to improve the bioavailability of SOD have been explored in recent decades. This review intends to describe the rationale that underlie the various approaches and chemical strategies that have led to the most recent advances in SOD delivery. This critical description includes SOD conjugates, SOD loaded into particulate carriers (micelles, liposomes, nanoparticles, microparticles) and the most promising and suitable formulations for oral delivery, with a particular emphasis on reports of preclinical/clinical results. Likely future directions are also considered and reported.
Topics: Administration, Oral; Biological Availability; Drug Compounding; Liposomes; Micelles; Nanoparticles; Oxidative Stress; Superoxide Dismutase
PubMed: 33242550
DOI: 10.1016/j.ijbiomac.2020.11.149 -
Geobiology Sep 2021The ability of aerobic microorganisms to regulate internal and external concentrations of the reactive oxygen species (ROS) superoxide directly influences the health and...
The ability of aerobic microorganisms to regulate internal and external concentrations of the reactive oxygen species (ROS) superoxide directly influences the health and viability of cells. Superoxide dismutases (SODs) are the primary regulatory enzymes that are used by microorganisms to degrade superoxide. SOD is not one, but three separate, non-homologous enzymes that perform the same function. Thus, the evolutionary history of genes encoding for different SOD enzymes is one of convergent evolution, which reflects environmental selection brought about by an oxygenated atmosphere, changes in metal availability, and opportunistic horizontal gene transfer (HGT). In this study, we examine the phylogenetic history of the protein sequence encoding for the nickel-binding metalloform of the SOD enzyme (SodN). The genomic potential to produce SodN is widespread among bacteria, including Actinobacteriota (Actinobacteria), Chloroflexota (Chloroflexi), Cyanobacteria, Proteobacteria, Patescibacteria, and others. The gene is also present in many archaea, with Thermoplasmatota and Nanoarchaeota representing the vast majority of archaeal sodN diversity. A comparison of organismal and SodN protein phylogenetic trees reveals several instances of HGT, including multiple inter-domain transfers of the sodN gene from the bacterial domain to the archaeal domain. Nearly half of the archaeal members with sodN live in the photic zone of the marine water column. The sodN gene is widespread and characterized by apparent vertical gene transfer in some sediment- or soil-associated lineages within the Actinobacteriota and Chloroflexota phyla, suggesting the ancestral sodN likely originated in one of these clades before expanding its taxonomic and biogeographic distribution to additional microbial groups in the surface ocean in response to decreasing iron availability. In addition to decreasing iron quotas, nickel-binding SOD has the added benefit of withstanding high reactant and product ROS concentrations without damaging the enzyme, making it particularly well suited for the modern surface ocean.
Topics: Amino Acid Sequence; Archaea; Bacteria; Gene Transfer, Horizontal; Nickel; Phylogeny; Superoxide Dismutase
PubMed: 33989454
DOI: 10.1111/gbi.12448 -
International Journal of Biological... Dec 2017A novel Cu/Zn-superoxide dismutase was extracted from Avicennia marina and purified. The sample was collected from Khamir port located in the north shore of Persian...
A novel Cu/Zn-superoxide dismutase was extracted from Avicennia marina and purified. The sample was collected from Khamir port located in the north shore of Persian Gulf. The purification procedure comprised of (NH)SO precipitation followed by CM-Sephadex C-50 and DEAE-Sepharose chromatography, and gel filtration chromatography (Sephadex G-75). The enzyme with a characteristic molecular weight of 31kDa, measured by SDS-page, showed its highest catalytic efficiency at pH 8.0 and 50°C. Its activity was greatly inhibited by cyanide and hydrogen peroxide. The pH profile showed that the enzyme could maintain most of its activity at pH values ranging from 5 to 10. The temperature profile of this enzyme showed a broad range of activity compared with other superoxide dismutases. Catalytic hydrolysis rate followed Michaelis-Menten equation. The values of k and K were obtained from Michaelis-Menten plot as 107000s and 11.5μmol respectively. The evidences from kinetic and thermodynamic parameters suggest that Avicennia marina superoxide dismutase (AmSOD) can be used as a suitable enzyme for biotechnological and pharmacological applications.
Topics: Antioxidants; Avicennia; Enzyme Stability; Hydrogen-Ion Concentration; Industry; Kinetics; Molecular Weight; Superoxide Dismutase; Temperature
PubMed: 28720545
DOI: 10.1016/j.ijbiomac.2017.07.054 -
Molecular Therapy : the Journal of the... Apr 2024The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve...
The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.
Topics: Mice; Humans; Animals; Cell Differentiation; Superoxide Dismutase; Adipocytes; Mesenchymal Stem Cells
PubMed: 38310354
DOI: 10.1016/j.ymthe.2024.01.031 -
International Journal of Pharmaceutics Jun 2023Aging is a dynamic and progressive process mediated by reactive oxygen species (ROS), and the antioxidant enzyme superoxide dismutase (SOD) can effectively scavenge ROS...
Aging is a dynamic and progressive process mediated by reactive oxygen species (ROS), and the antioxidant enzyme superoxide dismutase (SOD) can effectively scavenge ROS to extend longevity. However, the instability and impermeability of native enzyme limit its in vivo biomedical application. Currently, exosome as protein carriers attracts considerable attention in the disease treatment owing to low immunogenicity and high stability. Herein, SOD was encapsulated into exosomes via mechanical extrusion with saponin permeabilization to obtain SOD-loaded EXO (SOD@EXO). SOD@EXO with a hydrodynamic diameter of 101.7 ± 5.6 nm could scavenge excessive ROS and protect the cells from oxidative damage induced by 1-methyl-4-phenylpyridine. Compared with native SOD, SOD@EXO significantly extended the lifespan of N2 wild-type Caenorhabditis elegans under normal conditions. Moreover, SOD@EXO improved the resistance against heat and oxidative stress, leading to notable survival ratio under these hostile conditions. Overall, the exosome-mediated delivery of SOD could reduce ROS level and delay aging in C. elegans model, thereby providing potential strategies to treat ROS-related diseases in future.
Topics: Animals; Caenorhabditis elegans; Reactive Oxygen Species; Exosomes; Caenorhabditis elegans Proteins; Aging; Oxidative Stress; Superoxide Dismutase; Antioxidants
PubMed: 37268030
DOI: 10.1016/j.ijpharm.2023.123090 -
Characterization of the interaction between superoxide dismutase and 2-oxoisovalerate dehydrogenase.Gene Aug 2015Thermophiles are attractive microorganisms to study the adaptation of life in high temperature environment. It is revealed that superoxide dismutase (SOD) is essential...
Thermophiles are attractive microorganisms to study the adaptation of life in high temperature environment. It is revealed that superoxide dismutase (SOD) is essential for thermoadaptation of thermophiles. However, the SOD-mediated pathway of thermoadaptation remains unclear. To address this issue, the proteins interacted with SOD were characterized in Thermus thermophilus in this study. Based on co-immunoprecipitation and Western blot analyses, the results showed that 2-oxoisovalerate dehydrogenase α subunit was bound to SOD. The isothermal titration calorimetry analysis showed the existence of the interaction between SOD and 2-oxoisovalerate dehydrogenase α subunit. The bacterial two-hybrid data indicated that SOD was directly interacted with 2-oxoisovalerate dehydrogenase α subunit. Gene site-directed mutagenesis analysis revealed that the intracellular interaction between SOD and 2-oxoisovalerate dehydrogenase α subunit was dependent on their whole molecules. Therefore our study presented a novel aspect of SOD in the thermoadaptation of thermophiles by interaction with dehydrogenase, a key enzyme of tricarboxylic acid cycle.
Topics: 2-Oxoisovalerate Dehydrogenase (Acylating); Adaptation, Physiological; Amino Acid Sequence; Bacterial Proteins; Molecular Sequence Data; Protein Binding; Protein Interaction Domains and Motifs; Protein Interaction Mapping; Superoxide Dismutase; Thermodynamics; Thermus thermophilus
PubMed: 25958347
DOI: 10.1016/j.gene.2015.05.008 -
Molecular Biology Reports May 2020Superoxide dismutase is one of the key antioxidant enzymes accountable for the eradication of free radicals generated during various metabolic processes. This is first...
Superoxide dismutase is one of the key antioxidant enzymes accountable for the eradication of free radicals generated during various metabolic processes. This is first study reporting a thermostable MnSOD obtained from a xerophytic plant, Nerium oleander. The full-length gene identified using Rapid amplification of cDNA ends revealed an open reading frame of 699 bp flanked by 5'UTR and 3'UTR of 134 bp and 198 bp respectively. The corresponding NeMnSOD protein was cloned and expressed in Escherichia coli. The purified protein yields a band of 25.4 kDa, which established a specific activity of 2617 units mg of protein and under native condition yield bands of 52 kDa and 110 kDa, confirming the dimeric and tetrameric state of the protein. The Km and V of 0.078 ± 0.008 mM and 1052.3 ± 33.59 units mg of protein, respectively. The purified enzyme demonstrated thermostability by retaining more than 20% activity at a temperature 70 ℃. The enzyme functioned at pH range of 4-9.0 with maximum activity at pH 7.4. Sodium azide, effectively inhibited the activity of enzyme confirming it to be MnSOD. The enzyme activity was least affected on treatment with strong denaturants (Urea, guanidine HCl and SDS) and harsh chemicals (DTT, CHAPS and β-mercapto-ethanol) These experimental data validated with Insilco analysis revealed that NeMnSOD possessed thermo as well as kinetically stable moiety which can be further exploited with its applications in the field of pharmaceutical, food and cosmetic industry, which urge for such thermostable enzyme.
Topics: Amino Acid Sequence; Cloning, Molecular; Hydrogen-Ion Concentration; Kinetics; Manganese; Nerium; Open Reading Frames; Superoxide Dismutase; Temperature
PubMed: 32297289
DOI: 10.1007/s11033-020-05374-x -
Current Genetics Feb 2023Although copper is an essential trace element for cell function and viability, its excess can lead to protein oxidation, DNA cleavage, and ultimate cell damage. Cells...
Although copper is an essential trace element for cell function and viability, its excess can lead to protein oxidation, DNA cleavage, and ultimate cell damage. Cells have established a variety of regulatory mechanisms to ensure copper ion homeostasis. In Saccharomyces cerevisiae, copper sensing and response to copper deficiency are regulated by the transcription factor Mac1. Our group has previously reported that in addition to copper, several chromatin proteins modulate Mac1 functionality. In this study, based on a synthetic growth deficiency phenotype, we showed that the Cu/Zn superoxide dismutase Sod1 plays an important role in Mac1 transcriptional activity, in unchallenged nutrient-rich growth conditions. Sod1 is a multipotent cytoplasmic and mitochondrial enzyme, whose main known function is to detoxify the cell from superoxide ions. It has been previously reported that Sod1 also enters the nucleus and affects the transcription of several genes, some of which are involved in copper homeostasis under Cu-depleted (Wood and Thiele in J Biol Chem 284:404-413, 2009) or only under specific oxidative stress conditions (Dong et al. Mol Cell Biol 33:4041-4050, 2013; Tsang et al. Nar Commun 8:3446, 2014). We have shown that Sod1 physically interacts with Mac1 transcription factor and is important for the transactivation as well as its DNA-binding activities. On the other hand, a constitutively active mutant of Mac1 is not affected functionally by the Sod1 ablation, pointing out that Sod1 contributes to the maintenance of the copper-unchelated state of Mac1. In conclusion, we showed that Sod1-Mac1 interaction is vital for Mac1 functionality, regardless of copper medium deficiency, in unchallenged growth conditions, and we suggest that Sod1 enzymatic activity may modify the redox state of the cysteine-rich motifs in the Mac1 DNA-binding and transactivation domains.
Topics: Saccharomyces cerevisiae; Transcription Factors; Copper; Superoxide Dismutase-1; Saccharomyces cerevisiae Proteins; DNA; Zinc; Superoxide Dismutase; Nuclear Proteins
PubMed: 36456733
DOI: 10.1007/s00294-022-01258-8