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Phenotypic and genotypic characterization of antioxidant enzyme system in human population exposed to radiation from mobile towers.
Gulati, S, Yadav, A, Kumar, N, Priya, K, Aggarwal, NK, Gupta, R
Molecular and cellular biochemistry. 2018;(1-2):1-9
Abstract
In the present era, cellular phones have changed the life style of human beings completely and have become an essential part of their lives. The number of cell phones and cell towers are increasing in spite of their disadvantages. These cell towers transmit radiation continuously without any interruption, so people living within 100s of meters from the tower receive 10,000 to 10,000,000 times stronger signal than required for mobile communication. In the present study, we have examined superoxide dismutase (SOD) enzyme activity, catalase (CAT) enzyme activity, lipid peroxidation assay, and effect of functional polymorphism of SOD and CAT antioxidant genes against mobile tower-induced oxidative stress in human population. From our results, we have found a significantly lower mean value of manganese superoxide dismutase (MnSOD) enzyme activity, catalase (CAT) enzyme activity, and a high value of lipid peroxidation assay in exposed as compared to control subjects. Polymorphisms in antioxidant MnSOD and CAT genes significantly contributed to its phenotype. In the current study, a significant association of genetic polymorphism of antioxidant genes with genetic damage has been observed in human population exposed to radiations emitted from mobile towers.
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Trypsin Binding with Copper Ions Scavenges Superoxide: Molecular Dynamics-Based Mechanism Investigation.
Li, X, Zhong, Y, Zhao, C
International journal of environmental research and public health. 2018;(1)
Abstract
Trypsin is a serine protease, which has been proved to be a novel superoxide scavenger. The burst of superoxide induced by polychlorinated biphenyls can be impeded by trypsin in both wild type and sod knockout mutants of Escherichia coli. The experimental results demonstrated that the activities of superoxide scavenging of trypsin were significantly accelerated by Cu ions. Also, with the addition of Cu ions, a new β-sheet (β7) transited from a random coil in the Cu(II)-trypsin (TP) system, which was favorable for the formation of more contacts with other sheets of trypsin. Residue-residue network analysis and the porcupine plots proved that the Cu ion in trypsin strengthened some native interactions among residues, which ultimately resulted in much greater stability of the Cu(II)-TP system. Moreover, compact and stable trypsin structures with Cu ions might be responsible for significantly provoking the activity of superoxide scavenging.
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Metabolism of hydrogen sulfide (H2S) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase.
Olson, KR, Gao, Y, Arif, F, Arora, K, Patel, S, DeLeon, ER, Sutton, TR, Feelisch, M, Cortese-Krott, MM, Straub, KD
Redox biology. 2018;:74-85
Abstract
Reactive sulfur species (RSS) such as H2S, HS•, H2Sn, (n = 2-7) and HS2•- are chemically similar to H2O and the reactive oxygen species (ROS) HO•, H2O2, O2•- and act on common biological effectors. RSS were present in evolution long before ROS, and because both are metabolized by catalase it has been suggested that "antioxidant" enzymes originally evolved to regulate RSS and may continue to do so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved H2S, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (H2S2-H2S5). H2S was concentration- and oxygen-dependently oxidized by 1μM SOD to polysulfides (mainly H2S2, and to a lesser extent H2S3 and H2S5) with an EC50 of approximately 380μM H2S. H2S concentrations > 750μM inhibited SOD oxidation (IC50 = 1.25mM) with complete inhibition when H2S > 1.75mM. Polysulfides were not metabolized by SOD. SOD oxidation preferred dissolved H2S over hydrosulfide anion (HS-), whereas HS- inhibited polysulfide production. In hypoxia, other possible electron donors such as nitrate, nitrite, sulfite, sulfate, thiosulfate and metabisulfite were ineffective. Manganese SOD also catalyzed H2S oxidation to form polysulfides, but did not metabolize polysulfides indicating common attributes of these SODs. These experiments suggest that, unlike the well-known SOD-mediated dismutation of two O2•- to form H2O2 and O2, SOD catalyzes a reaction using H2S and O2 to form persulfide. These can then combine in various ways to form polysulfides and sulfur oxides. It is also possible that H2S (or polysulfides) interact/react with SOD cysteines to affect catalytic activity or to directly contribute to sulfide metabolism. Our studies suggest that H2S metabolism by SOD may have been an ancient mechanism to detoxify sulfide or to regulate RSS and along with catalase may continue to do so in contemporary organisms.
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Association between MnSOD Val16Ala Polymorphism and Cancer Risk: Evidence from 33,098 Cases and 37,831 Controls.
Wang, P, Zhu, Y, Xi, S, Li, S, Zhang, Y
Disease markers. 2018;:3061974
Abstract
Manganese superoxide dismutase (MnSOD) plays a critical role in the defense against reactive oxygen species. The association between MnSOD Val16Ala polymorphism and cancer risk has been widely studied, but the results are contradictory. To obtain more precision on the association, we performed the current meta-analysis with 33,098 cases and 37,831 controls from 88 studies retrieved from PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association. We found that the polymorphism was associated with an increased overall cancer risk (homozygous: OR = 1.09, 95% CI = 1.00-1.19; heterozygous: OR = 1.07, 95% CI = 1.02-1.12; dominant: OR = 1.08, 95% CI = 1.02-1.14; and allele comparison: OR = 1.06, 95% CI = 1.02-1.11). Stratification analysis further showed an increased risk for prostate cancer, Asians, Caucasians, population-based studies, hospital-based studies, low quality and high quality studies. However, the increased risk for MnSOD Val16Ala polymorphism among Asians needs further validation based on the false-positive report probability (FPRP) test. To summarize, this meta-analysis suggests that the MnSOD Val16Ala polymorphism is associated with significantly increased cancer risk, which needs further validation in single large studies.
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The Effect of a Short-Term Exposure to Lead on the Levels of Essential Metal Ions, Selected Proteins Related to Them, and Oxidative Stress Parameters in Humans.
Dobrakowski, M, Boroń, M, Birkner, E, Kasperczyk, A, Chwalińska, E, Lisowska, G, Kasperczyk, S
Oxidative medicine and cellular longevity. 2017;:8763793
Abstract
The present study was designed to explore the possible influence of subacute exposure to lead on the levels of selected essential metals, selected proteins related to them, and oxidative stress parameters in occupationally exposed workers. The study population included 36 males occupationally exposed to lead for 36 to 44 days. Their blood lead level at the beginning of the study was 10.7 ± 7.67 μg/dl and increased to the level of 49.1 ± 14.1 μg/dl at the end of the study. The levels of calcium, magnesium, and zinc increased significantly after lead exposure compared to baseline by 3%, 3%, and 8%, respectively, while the level of copper decreased significantly by 7%. The malondialdehyde (MDA) level and the activities of catalase (CAT) and superoxide dismutase (SOD) did not change due to lead exposure. However, the level of lipid hydroperoxides (LPH) in serum increased significantly by 46%, while the level of erythrocyte lipofuscin (LPS) decreased by 13%. The serum levels of essential metals are modified by a short-term exposure to lead in occupationally exposed workers. A short-term exposure to lead induces oxidative stress associated with elevated levels of LPH but not MDA.
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Evaluating a Gene-Environment Interaction in Amyotrophic Lateral Sclerosis: Methylmercury Exposure and Mutated SOD1.
Bailey, JM, Colón-Rodríguez, A, Atchison, WD
Current environmental health reports. 2017;(2):200-207
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Abstract
PURPOSE OF REVIEW Gene-environment (GxE) interactions likely contribute to numerous diseases, but are often difficult to model in the laboratory. Such interactions have been widely hypothesized for amyotrophic lateral sclerosis (ALS); recent controlled laboratory studies are discussed here and hypotheses related to possible mechanisms of action are offered. Using methylmercury exposure and mutated SOD1 to model the impacts of such an interaction, we interpret evidence about their respective mechanisms of toxicity to interrogate the possibility of additive (or synergistic) effects when combined. RECENT FINDINGS Recent work has converged on mechanisms of calcium-mediated glutamate excitotoxicity as a likely contributor in one model of a gene-environment interaction affecting the onset and progression of ALS-like phenotype. The current experimental literature on mechanisms of metal-induced neuronal injury and their relevant interactions with genetic contributions in ALS is sparse, but we describe those studies here and offer several integrative hypotheses about the likely mechanisms involved.
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Association of the C47T polymorphism in superoxide dismutase gene 2 with noise-induced hearing loss: a meta-analysis.
Wang, J, Li, J, Peng, K, Fu, ZY, Tang, J, Yang, MJ, Chen, QC
Brazilian journal of otorhinolaryngology. 2017;(1):80-87
Abstract
INTRODUCTION Currently, there is limited information about the relationship between manganese superoxide dismutase (sod2) c47t polymorphism and susceptibility to noise-induced hearing loss (NIHL). OBJECTIVE The aim of this meta-analysis was to clarify the association between SOD2 C47T polymorphism and NIHL. METHODS A search in PubMed and Web of Science was performed to collect data. All full-text, English-written studies containing sufficient and complete case-and-control data about the relationship between SOD2 C47T polymorphism and NIHL were included. Three eligible studies, comprising 1094 subjects, were identified. pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated to evaluate the strength of the association between SOD2 C47T polymorphism and NIHL. RESULTS No significant association between C47T polymorphism and risk of NIHL was found with the following combinations: T vs. C (OR=0.83; 95% CI=0.63-1.09); TT vs. CC (OR=0.49; 95% CI=0.22-1.09); CT vs. CC (OR=0.54; 95% CI=0.25-1.17); TT vs. CC+CT (OR=0.82; 95% CI=0.50-1.32); CC vs. TT+TC (OR=0.49; 95% CI=0.23-1.04). However, in subgroup analysis, a significant association was found for TT vs. CC+CT (OR=0.77; 95% CI=0.42-1.41) in the Chinese population. CONCLUSION The present meta-analysis suggests that SOD2 C47T polymorphism is significantly associated with increased risk of NIHL in the Chinese population. Further large and well-designed studies are needed to confirm this association.
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Challenges encountered during development of Mn porphyrin-based, potent redox-active drug and superoxide dismutase mimic, MnTnBuOE-2-PyP5+, and its alkoxyalkyl analogues.
Rajic, Z, Tovmasyan, A, de Santana, OL, Peixoto, IN, Spasojevic, I, do Monte, SA, Ventura, E, Rebouças, JS, Batinic-Haberle, I
Journal of inorganic biochemistry. 2017;:50-60
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Abstract
We disclose here the studies that preceded and guided the preparation of the metal-based, redox-active therapeutic Mn(III) meso-tetrakis(N-n-butoxyethylpyridyl)porphyrin, MnTnBuOE-2-PyP5+ (BMX-001), which is currently in Phase I/II Clinical Trials at Duke University (USA) as a radioprotector of normal tissues in cancer patients. N-substituted pyridylporphyrins are ligands for Mn(III) complexes that are among the most potent superoxide dismutase mimics thus far synthesized. To advance their design, thereby improving their physical and chemical properties and bioavailability/toxicity profiles, we undertook a systematic study on placing oxygen atoms into N-alkylpyridyl chains via alkoxyalkylation reaction. For the first time we show here the unforeseen structural rearrangement that happens during the alkoxyalkylation reaction by the corresponding tosylates. Comprehensive experimental and computational approaches were employed to solve the rearrangement mechanism involved in quaternization of pyridyl nitrogens, which, instead of a single product, led to a variety of mixed N-alkoxyalkylated and N-alkylated pyridylporphyrins. The rearrangement mechanism involves the formation of an intermediate alkyl oxonium cation in a chain-length-dependent manner, which subsequently drives differential kinetics and thermodynamics of competing N-alkoxyalkylation versus in situ N-alkylation. The use of alkoxyalkyl tosylates, of different length of alkyl fragments adjacent to oxygen atom, allowed us to identify the set of alkyl fragments that would result in the synthesis of a single compound of high purity and excellent therapeutic potential.
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Expression and polymorphism (rs4880) of mitochondrial superoxide dismutase (SOD2) and asparaginase induced hepatotoxicity in adult patients with acute lymphoblastic leukemia.
Alachkar, H, Fulton, N, Sanford, B, Malnassy, G, Mutonga, M, Larson, RA, Bloomfield, CD, Marcucci, G, Nakamura, Y, Stock, W
The pharmacogenomics journal. 2017;(3):274-279
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Abstract
Asparaginase, which depletes asparagine and glutamine, activates amino-acid stress response. Oxidative stress mediated by excessive reactive oxygen species (ROS) causes enhanced mitochondrial permeabilization and subsequent cell apoptosis and is considered as a plausible mechanism for drug-induced hepatotoxicity, a common toxicity of asparaginase in adults with acute lymphoblastic leukemia (ALL). Studies investigating the pharmacogenetics of asparaginase in ALL are limited and focused on asparaginase-induced allergic reaction common in pediatric patients. Here, we sought to determine a potential association between the variant rs4880 in SOD2 gene, a key mitochondrial enzyme that protects cells against ROS, and hepatotoxicity during asparaginase-based therapy in 224 patients enrolled on CALGB-10102, a treatment trial for adults with ALL. We report that the CC genotype of rs4880 is associated with increased hepatotoxicity following asparaginase-based treatment. Thus, rs4880 likely contributes to asparaginase-induced hepatotoxicity, and functional studies investigating this single-nucleotide polymorphism (SNP) are needed to develop therapeutic approaches that mitigate this toxicity.
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Mineral status and superoxide dismutase enzyme activity in Alzheimer's disease.
Rodrigues, GP, Cozzolino, SMF, Marreiro, DDN, Caldas, DRC, da Silva, KG, de Sousa Almondes, KG, Neto, JMM, Pimentel, JAC, de Carvalho, CMRG, Nogueira, NDN
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2017;:83-87
Abstract
The study evaluated the dietary intake of zinc and copper, as measured by plasma and erythrocyte concentrations, the Cu/Zn ratio and measure the erythrocyte superoxide dismutase enzyme (eSOD) activity and the relationship between these markers and the degree of dementia in elderly individuals with and without Alzheimer's Disease (AD). A total of 93 elderly people aged 60-94 years were divided into two groups: with AD (n=44) and without AD (n=49). The NINCDS-ADRDA criteria were used for diagnosing AD, and dementia staging was determined using the Clinical Dementia Rating (CDR) scale. The dietary intake of Zn and Cu was obtained from a standard 3-day food record. Plasma and erythrocyte concentrations of the minerals were determined by flame atomic absorption spectrophotometry and by measuring eSOD activity in an automatic biochemical analyzer. The results showed dietary intake of Zn and Cu above the reference values with no differences observed between the two groups (p>0.05). Plasma and erythrocyte normocupremia as well as alteration in the Zn pool, with its reduced plasma concentrations and high in the erythrocytes, were observed in both groups (p>0.05). The plasma Cu/Zn ratio were not significantly different in patients with and without AD (p>0.05). The eSOD activity was high in both patient groups (p>0.05). However, among elderly patients with AD there was a positive correlation between this marker and dementia severity. According to our study results, we conclude that plasma and erythrocyte concentrations of Cu and Zn, as well as Cu/Zn ratio among elderly individuals is not related to Alzheimer's Disease. However, antioxidant activity of eSOD is associated with dementia severity.