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1.
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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2.
Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells.
Kikuchi, H, Mimuro, H, Kuribayashi, F
Biochemical and biophysical research communications. 2018;(1):1195-1200
Abstract
The membrane bound cytochrome b558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O2-)-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O2--generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O2--generating activity increased more than 5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and resveratrol strongly enhanced transcription of the gp91-phox compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and resveratrol caused remarkable accumulation of protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4-fold) compared with those of the RA-treatment alone. In addition, ChIP assay suggested that resveratrol participates in enhancing the gene expression of gp91-phox via promoting acetylation of Lys-9 residues and Lys-14 residues of histone H3 within chromatin around the promoter regions of the gene. These results suggested that resveratrol strongly enhances the RA-induced O2--generating activity via up-regulation of gp91-phox gene expression in U937 cells.
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3.
A sensitively non-enzymatic amperometric sensor and its application in living cell superoxide anion radical detection.
Liu, X, Ran, M, Liu, G, Liu, X, Xue, Z, Lu, X
Talanta. 2018;:248-255
Abstract
Here, we report a nanocomposite composed of silver nanoparticles and multi-walled carbon nanotubes (AgNPs/MWNTs) utilized as an efficient electrode material for sensitive detection superoxide anion (O2•-). The procedure to synthesize AgNPs/MWNTs nanocomposites was green and facile. In the presence of functionalized multi-wall carbon nanotubes (MWNTs), silver nanoparticles (AgNPs) were in situ generated by chemical reduction of silver nitrate with glucose as a reducing and stabilizing agent to give the desired AgNPs/MWNTs nanocomposites. The nanocomposites can be easily used for the construction of an electrochemical sensor on glassy carbon electrode (GCE). The characterization of sensor and experimental parameters affecting its activity were investigated employing scanning electron microscopy (SEM), energy-dispersive X-ray spectrometer (EDS), X-ray diffraction (XRD), and cyclic voltammetry (CV). The resulted sensor exhibited favorable electrochemical performance for O2•- sensing with a low detection limit of 0.1192 nM and wide linear range of 6 orders of magnitude, which guarantees the capacity of sensitive and credible detection of O2•- released from living cells. Notably, a simulation experiment indicated the capacity to resist oxidative stress is limited in biological milieu. Thus this work has great potential for further applications in biological researches.
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4.
Cirrhotic patients with minimal hepatic encephalopathy have increased capacity to eliminate superoxide and peroxynitrite in lymphocytes, associated with cognitive impairment.
Giménez-Garzó, C, Urios, A, Agustí, A, Mangas-Losada, A, García-García, R, Escudero-García, D, Kosenko, E, Ordoño, JF, Tosca, J, Giner-Durán, R, et al
Free radical research. 2018;(1):118-133
Abstract
Patients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxide (plumbagin) or nitric oxide (NOR-1) to assess the capacity to eliminate them. Under basal conditions, MHE patients show reduced superoxide and peroxynitrite levels and increased nitric oxide (NO) and nitrotyrosine levels. In patients without MHE plumbagin strongly increases cellular superoxide, moderately peroxynitrite and reduces NO levels. In MHE patients, plumbagin increases slightly superoxide and strongly peroxynitrite levels and affects slightly NO levels. NOR-1 increases NO levels much less in patients with than without MHE. These data show that the mechanisms and the capacity to eliminate cellular superoxide, NO and peroxynitrite are enhanced in MHE patients. Superoxide elimination is enhanced through reaction with NO to form peroxynitrite which, in turn, is eliminated by enhanced reaction with biological molecules, which could contribute to cognitive impairment in MHE. The data show that basal free radical levels do not reflect the oxidative stress status in MHE.
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5.
Polysulfides and products of H2S/S-nitrosoglutathione in comparison to H2S, glutathione and antioxidant Trolox are potent scavengers of superoxide anion radical and produce hydroxyl radical by decomposition of H2O2.
Misak, A, Grman, M, Bacova, Z, Rezuchova, I, Hudecova, S, Ondriasova, E, Krizanova, O, Brezova, V, Chovanec, M, Ondrias, K
Nitric oxide : biology and chemistry. 2018;:136-151
Abstract
Exogenous and endogenously produced sulfide derivatives, such as H2S/HS-/S2-, polysulfides and products of the H2S/S-nitrosoglutathione interaction (S/GSNO), affect numerous biological processes in which superoxide anion (O2-) and hydroxyl (OH) radicals play an important role. Their cytoprotective-antioxidant and contrasting pro-oxidant-toxic effects have been reported. Therefore, the aim of our work was to contribute to resolving this apparent inconsistency by studying sulfide derivatives/free radical interactions and their consequent biological effects compared to the antioxidants glutathione (GSH) and Trolox. Using the electron paramagnetic resonance (EPR) spin trapping technique and O2-, we found that a polysulfide (Na2S4) and S/GSNO were potent scavengers of O2- and cPTIO radicals compared to H2S (Na2S), GSH and Trolox, and S/GSNO scavenged the DEPMPO-OH radical. As detected by the EPR spectra of DEPMPO-OH, the formation of OH in physiological solution by S/GSNO was suggested. All the studied sulfide derivatives, but not Trolox or GSH, had a bell-shaped potency to decompose H2O2 and produced OH in the following order: S/GSNO > Na2S4 ≥ Na2S > GSH = Trolox = 0, but they scavenged OH at higher concentrations. In studies of the biological consequences of these sulfide derivatives/H2O2 properties, we found the following: (i) S/GSNO alone and all sulfide derivatives in the presence of H2O2 cleaved plasmid DNA; (ii) S/GSNO interfered with viral replication and consequently decreased the infectivity of viruses; (iii) the sulfide derivatives induced apoptosis in A2780 cells but inhibited apoptosis induced by H2O2; and (iv) Na2S4 modulated intracellular calcium in A87MG cells, which depended on the order of Na2S4/H2O2 application. We suggest that the apparent inconsistency of the cytoprotective-antioxidant and contrasting pro-oxidant-toxic biological effects of sulfide derivatives results from their time- and concentration-dependent radical production/scavenging properties and their interactions with O2-, OH and H2O2. The results imply a direct involvement of sulfide derivatives in O2- and H2O2/OH free radical pathways modulating antioxidant/toxic biological processes.
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6.
MnSOD mediates shear stress-promoted tumor cell migration and adhesion.
Ma, S, Fu, A, Lim, S, Chiew, GGY, Luo, KQ
Free radical biology & medicine. 2018;:46-58
Abstract
Circulation of cancer cells in the bloodstream is a vital step for distant metastasis, during which cancer cells are exposed to hemodynamic shear stress (SS). The actions of SS on tumor cells are complicated and not fully understood. We previously reported that fluidic SS was able to promote migration of breast cancer cells by elevating the cellular ROS level. In this study, we further investigated the mechanisms regulating SS-promoted cell migration and identified the role of MnSOD in the related pathway. We found that SS could enhance tumor cell adhesion to extracellular matrix and endothelial monolayer, and MnSOD also regulated this process. Briefly, SS stimulates the generation of mitochondrial superoxide in tumor cells. MnSOD then converts superoxide into hydrogen peroxide, which activates ERK1/2 to promote tumor cell migration and activates FAK to promote tumor cell adhesion. Combining our previous and present studies, we present experimental evidence on the pro-metastatic effects of hemodynamic SS and reveal the underlying mechanism. Our findings provide new insights into the nature of cancer metastasis and the understanding of tumor cell responses to external stresses and have valuable implications for cancer therapy development.
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7.
[Modifications of the superoxide anion level in breast milk by the intake of flavonoids and carotenoids].
Marchesino, MA, Cortez, MV, Albrecht, C, Aballay, LR, Soria, EA
Salud publica de Mexico. 2017;(5):526-531
Abstract
OBJECTIVE To associate the intake of flavonoids and carotenoids with the breast milk level of superoxide anion, as an oxidative stress marker. MATERIALS AND METHODS 100 women from Cordoba (Argentina), who breastfed within the first postpartum 6 months, were studied during the 2013-2015 period, by evaluating their sanitary data, food intake and anion level in milk with multiple logistic regression. RESULTS The intake of flavonoids, provitamin A carotenoids and non-provitamin carotenoids was 72 (61) mg/d, 1813 (1 657) µg/d y 5427 (3 664) µg/d, respectively. The anion was associated with the intake of flavanols (OR=1.081; CI95 1.001-1.167) y flavanones (OR=1.025; CI95 1.001-1.048). This effect was not seen with other flavonoids and carotenoids. CONCLUSIONS Intake of flavanols and flavanones increases milk oxidation risk, which is relevant to develop diet recommendations.
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8.
Recent developments in detection of superoxide radical anion and hydrogen peroxide: Opportunities, challenges, and implications in redox signaling.
Kalyanaraman, B, Hardy, M, Podsiadly, R, Cheng, G, Zielonka, J
Archives of biochemistry and biophysics. 2017;:38-47
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Free full text
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Abstract
In this review, some of the recent developments in probes and assay techniques specific for superoxide (O2-) and hydrogen peroxide (H2O2) are discussed. Over the last decade, significant progress has been made in O2- and H2O2 detection due to syntheses of new redox probes, better understanding of their chemistry, and development of specific and sensitive assays. For superoxide detection, hydroethidine (HE) is the most suitable probe, as the product, 2-hydroxyethidium, is specific for O2-. In addition, HE-derived dimeric products are specific for one-electron oxidants. As red-fluorescent ethidium is always formed from HE intracellularly, chromatographic techniques are required for detecting 2-hydroxyethidium. HE analogs, Mito-SOX and hydropropidine, exhibit the same reaction chemistry with O2- and one-electron oxidants. Thus, mitochondrial superoxide can be unequivocally detected using HPLC-based methods and not by fluorescence microscopy. Aromatic boronate-based probes react quantitatively with H2O2, forming a phenolic product. However, peroxynitrite and hypochlorite react more rapidly with boronates, forming the same product. Using ROS-specific probes and HPLC assays, it is possible to screen chemical libraries to discover specific inhibitors of NADPH oxidases. We hope that rigorous detection of O2- and H2O2 in different cellular compartments will improve our understanding of their role in redox signaling.
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9.
Lead-induced stress, which triggers the production of nitric oxide (NO) and superoxide anion (O2·-) in Arabidopsis peroxisomes, affects catalase activity.
Corpas, FJ, Barroso, JB
Nitric oxide : biology and chemistry. 2017;:103-110
Abstract
Lead (Pb) contamination has a toxic effect on plant metabolisms, leading to a decrease in biomass production. The free radical nitric oxide (NO) is involved in the mechanism of response to a wide range of abiotic stresses. However, little is known about the interplay between Pb-induced stress and NO metabolism. Peroxisomes are sub-cellular compartments involved in multiple cellular metabolic pathways which are characterized by an active nitro-oxidative metabolism. Thus, Arabidopsis thaliana mutants expressing cyan fluorescent protein (CFP) through the addition of peroxisomal targeting signal 1 (PTS1), which enables peroxisomes to be visualized in vivo by confocal laser scanning microscopy (CLSM) combined with fluorescent probes for nitric oxide (NO), superoxide anion (O2·-) and peroxynitrite (ONOO-), were used to evaluate the potential involvement of these organelles in the mechanism of response to 150 μM lead-induced stress. Both NO and O2·- radicals, and consequently ONOO-, were overproduced under Pb-stress. Additionally, biochemical and gene expression analyses of peroxisomal enzymes, including the antioxidant catalase (CAT) and two photorespiration enzymes, such as glycolate oxidase (GOX) and hydroxypyruvate reductase (HPR), show that, under Pb-stress, only the catalase was negatively affected, while the two photorespiration enzymes remained unaffected. These results corroborate the involvement of plant peroxisomal metabolisms in the mechanism of response to lead contamination and highlight the importance of the peroxisomal NO metabolism.
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10.
Redox Signaling Regulated by Cysteine Persulfide and Protein Polysulfidation.
Kasamatsu, S, Nishimura, A, Morita, M, Matsunaga, T, Abdul Hamid, H, Akaike, T
Molecules (Basel, Switzerland). 2016;(12)
Abstract
For decades, reactive persulfide species including cysteine persulfide (CysSSH) have been known to exist endogenously in organisms. However, the physiological significance of endogenous persulfides remains poorly understood. That cystathionine β-synthase and cystathionine γ-lyase produced CysSSH from cystine was recently demonstrated. An endogenous sulfur transfer system involving CysSSH evidently generates glutathione persulfide (GSSH) that exists at concentrations greater than 100 μM in vivo. Because reactive persulfide species such as CysSSH and GSSH have higher nucleophilicity than parental cysteine (Cys) and glutathione do, these reactive species exhibit strong scavenging activities against oxidants, e.g., hydrogen peroxide, and electrophiles, which contributes to redox signaling regulation. Also, several papers indicated that various proteins and enzymes have Cys polysulfides including CysSSH at their specific Cys residues, which is called protein polysulfidation. Apart from the redox signaling regulatory mechanism, another plausible function of protein polysulfidation is providing protection for protein thiol residues against irreversible chemical modification caused by oxidants and electrophiles. Elucidation of the redox signaling regulatory mechanism of reactive persulfide species including small thiol molecules and thiol-containing proteins should lead to the development of new therapeutic strategies and drug discoveries for oxidative and electrophilic stress-related diseases.