Single-bilayer graphene oxide sheet tolerance and glutathione redox system significance assessment in faba bean (Vicia faba L.)

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Anjum, Naser A. [University of Aveiro, Centre for Environmental and Marine Studies (CESAM) and Department of Chemistry (Portugal); Singh, Neetu; Singh, Manoj K. [University of Aveiro, Center for Mechanical Technology and Automation (TEMA) and Department of Mechanical Engineering (Portugal); Shah, Zahoor A. [University of Toledo, Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences (United States); Duarte, Armando C.; Pereira, Eduarda; Ahmad, Iqbal, E-mail: ahmadr@ua.pt [University of Aveiro, Centre for Environmental and Marine Studies (CESAM) and Department of Chemistry (Portugal)

2013-07-15

Adsorbents based on single-bilayer graphene oxide sheet (hereafter termed 'graphene oxide') are widely used in contaminated environments cleanup which may easily open the avenues for their entry to different environmental compartments, exposure to organisms and their subsequent transfer to human/animal food chain. Considering a common food crop-faba bean (Vicia faba L.) germinating seedlings as a model plant system, this study assesses the V. faba-tolerance to different concentrations (0, 100, 200, 400, 800, and 1600 mg L{sup -1}) of graphene oxide (0.5-5 {mu}m) and evaluates glutathione ({gamma}-glutamyl-cysteinyl-glycine) redox system significance in this context. The results showed significantly increased V. faba sensitivity under three graphene oxide concentrations (in order of impact: 1,600 > 200 > 100 mg graphene oxide L{sup -1}), which was accompanied by decreased glutathione redox (reduced glutathione-to-oxidized glutathione) ratio, reduced glutathione pool, as well as significant and equally elevated activities of glutathione-regenerating (glutathione reductase) and glutathione-metabolizing (glutathione peroxidase; glutathione sulfo-transferase) enzymes. Contrarily, the two graphene oxide concentrations (in order of impact: 800 > 400 graphene oxide mg L{sup -1}) yielded promising results; where, significant improvements in V. faba health status (measured as increased graphene oxide tolerance) were clearly perceptible with increased ratio of the reduced glutathione-to-oxidized glutathione, reduced glutathione pool and glutathione reductase activity but decreased activities of glutathione-metabolizing enzymes. It is inferred that V. faba seedlings-sensitivity and/or tolerance to graphene oxide concentrations depends on both the cellular redox state (reduced glutathione-to-oxidized glutathione ratio) and the reduced glutathione pool which in turn are controlled by a finely tuned modulation of the coordination between glutathione-regenerating and

Degree of glutathione deficiency and redox imbalance depend on subtype of mitochondrial disease and clinical status.

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Gregory M Enns

Full Text Available Mitochondrial disorders are associated with decreased energy production and redox imbalance. Glutathione plays a central role in redox signaling and protecting cells from oxidative damage. In order to understand the consequences of mitochondrial dysfunction on in vivo redox status, and to determine how this varies by mitochondrial disease subtype and clinical severity, we used a sensitive tandem mass spectrometry assay to precisely quantify whole blood reduced (GSH and oxidized (GSSG glutathione levels in a large cohort of mitochondrial disorder patients. Glutathione redox potential was calculated using the Nernst equation. Compared to healthy controls (n = 59, mitochondrial disease patients (n = 58 as a group showed significant redox imbalance (redox potential -251 mV ± 9.7, p<0.0001 with an increased level of oxidation by ∼ 9 mV compared to controls (-260 mV ± 6.4. Underlying this abnormality were significantly lower whole blood GSH levels (p = 0.0008 and GSH/GSSG ratio (p = 0.0002, and significantly higher GSSG levels (p<0.0001 in mitochondrial disease patients compared to controls. Redox potential was significantly more oxidized in all mitochondrial disease subgroups including Leigh syndrome (n = 15, electron transport chain abnormalities (n = 10, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (n = 8, mtDNA deletion syndrome (n = 7, mtDNA depletion syndrome (n = 7, and miscellaneous other mitochondrial disorders (n = 11. Patients hospitalized in metabolic crisis (n = 7 showed the greatest degree of redox imbalance at -242 mV ± 7. Peripheral whole blood GSH and GSSG levels are promising biomarkers of mitochondrial dysfunction, and may give insights into the contribution of oxidative stress to the pathophysiology of the various mitochondrial disorders. In particular, evaluation of redox potential may be useful in monitoring of clinical status or response to redox-modulating therapies in clinical trials.

Effect of supplementation with methionine and different fat sources on the glutathione redox system of growing chickens.

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Németh, Katalin; Mézes, M; Gaál, T; Bartos, A; Balogh, K; Husvéth, F

2004-01-01

The effect of supplementary methionine and fats of different saturation levels on the glutathione redox system of growing broiler cockerels was studied. The diet of three groups of chicks was supplemented with corn germ oil, beef tallow and fish oil at the levels of 30 g/kg and 50 g/kg of feed, respectively. The diet of further three groups was supplemented with methionine (5 g/kg of feed) in addition to the different fat sources. Control chicks were fed with a compound feed without methionine and fat supplementation. Reduced glutathione (GSH) and glutathione disulphide (GSSG) content as well as glutathione peroxidase activity in the liver were determined and GSH/GSSG ratio was calculated at day old and then at one and three weeks of age. Our results indicate that supplementary methionine stimulates both the synthesis of the glutathione redox system and glutathione peroxidase activity in growing chickens in the first period of postnatal life, when the risk of lipid peroxidation is high due to feeding unsaturated fats in the diet.

Real-time quantification of subcellular H2O2 and glutathione redox potential in living cardiovascular tissues.

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Panieri, Emiliano; Millia, Carlo; Santoro, Massimo M

2017-08-01

Detecting and measuring the dynamic redox events that occur in vivo is a prerequisite for understanding the impact of oxidants and redox events in normal and pathological conditions. These aspects are particularly relevant in cardiovascular tissues wherein alterations of the redox balance are associated with stroke, aging, and pharmacological intervention. An ambiguous aspect of redox biology is how redox events occur in subcellular organelles including mitochondria, and nuclei. Genetically-encoded Rogfp2 fluorescent probes have become powerful tools for real-time detection of redox events. These probes detect hydrogen peroxide (H 2 O 2 ) levels and glutathione redox potential (E GSH ), both with high spatiotemporal resolution. By generating novel transgenic (Tg) zebrafish lines that express compartment-specific Rogfp2-Orp1 and Grx1-Rogfp2 sensors we analyzed cytosolic, mitochondrial, and the nuclear redox state of endothelial cells and cardiomyocytes of living zebrafish embryos. We provide evidence for the usefulness of these Tg lines for pharmacological compounds screening by addressing the blocking of pentose phosphate pathways (PPP) and glutathione synthesis, thus altering subcellular redox state in vivo. Rogfp2-based transgenic zebrafish lines represent valuable tools to characterize the impact of redox changes in living tissues and offer new opportunities for studying metabolic driven antioxidant response in biomedical research. Copyright © 2017 Elsevier Inc. All rights reserved.

Proteomic and activity profiles of ascorbate-glutathione cycle enzymes in germinating barley embryo

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Bønsager, Birgit Christine; Shahpiri, Azar; Finnie, Christine

2010-01-01

Enzymes involved in redox control are important during seed germination and seedling growth. Ascorbate-glutathione cycle enzymes in barley embryo extracts were monitored both by 2D-gel electrophoresis and activity measurements from 4 to 144 h post imbibition (PI). Strikingly different activity...... profiles were observed. No ascorbate peroxidase (APX) activity was present in mature seeds but activity was detected after 24 h PI and increased 14-fold up to 144 h PI. In contrast, dehydroascorbate reductase (DHAR) activity was present at 4 h PI and first decreased by 9-fold until 72 h PI followed by a 5......-fold increase at 144 h PI. Glutathione reductase and monodehydroascorbate reductase activities were also detected at 4 h PI, and showed modest increases of 1.8- and 2.7-fold, respectively, by 144 h PI. The combination of functional analysis with the proteomics approach enabled correlation...

Low glutathione regulates gene expression and the redox potentials of the nucleus and cytosol in Arabidopsis thaliana.

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Schnaubelt, Daniel; Queval, Guillaume; Dong, Yingping; Diaz-Vivancos, Pedro; Makgopa, Matome Eugene; Howell, Gareth; De Simone, Ambra; Bai, Juan; Hannah, Matthew A; Foyer, Christine H

2015-02-01

Reduced glutathione (GSH) is considered to exert a strong influence on cellular redox homeostasis and to regulate gene expression, but these processes remain poorly characterized. Severe GSH depletion specifically inhibited root meristem development, while low root GSH levels decreased lateral root densities. The redox potential of the nucleus and cytosol of Arabidopsis thaliana roots determined using roGFP probes was between -300 and -320 mV. Growth in the presence of the GSH-synthesis inhibitor buthionine sulfoximine (BSO) increased the nuclear and cytosolic redox potentials to approximately -260 mV. GSH-responsive genes including transcription factors (SPATULA, MYB15, MYB75), proteins involved in cell division, redox regulation (glutaredoxinS17, thioredoxins, ACHT5 and TH8) and auxin signalling (HECATE), were identified in the GSH-deficient root meristemless 1-1 (rml1-1) mutant, and in other GSH-synthesis mutants (rax1-1, cad2-1, pad2-1) as well as in the wild type following the addition of BSO. Inhibition of auxin transport had no effect on organ GSH levels, but exogenous auxin decreased the root GSH pool. We conclude that GSH depletion significantly increases the redox potentials of the nucleus and cytosol, and causes arrest of the cell cycle in roots but not shoots, with accompanying transcript changes linked to altered hormone responses, but not oxidative stress. © 2013 John Wiley & Sons Ltd.

Glutathione.

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Noctor, Graham; Queval, Guillaume; Mhamdi, Amna; Chaouch, Sejir; Foyer, Christine H

2011-01-01

Glutathione is a simple sulfur compound composed of three amino acids and the major non-protein thiol in many organisms, including plants. The functions of glutathione are manifold but notably include redox-homeostatic buffering. Glutathione status is modulated by oxidants as well as by nutritional and other factors, and can influence protein structure and activity through changes in thiol-disulfide balance. For these reasons, glutathione is a transducer that integrates environmental information into the cellular network. While the mechanistic details of this function remain to be fully elucidated, accumulating evidence points to important roles for glutathione and glutathione-dependent proteins in phytohormone signaling and in defense against biotic stress. Work in Arabidopsis is beginning to identify the processes that govern glutathione status and that link it to signaling pathways. As well as providing an overview of the components that regulate glutathione homeostasis (synthesis, degradation, transport, and redox turnover), the present discussion considers the roles of this metabolite in physiological processes such as light signaling, cell death, and defense against microbial pathogen and herbivores.

Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators.

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Foyer, Christine H; Wilson, Michael H; Wright, Megan H

2018-03-29

Plant stem cells are the foundation of plant growth and development. The balance of quiescence and division is highly regulated, while ensuring that proliferating cells are protected from the adverse effects of environment fluctuations that may damage the genome. Redox regulation is important in both the activation of proliferation and arrest of the cell cycle upon perception of environmental stress. Within this context, reactive oxygen species serve as 'pro-life' signals with positive roles in the regulation of the cell cycle and survival. However, very little is known about the metabolic mechanisms and redox-sensitive proteins that influence cell cycle progression. We have identified cysteine residues on known cell cycle regulators in Arabidopsis that are potentially accessible, and could play a role in redox regulation, based on secondary structure and solvent accessibility likelihoods for each protein. We propose that redox regulation may function alongside other known posttranslational modifications to control the functions of core cell cycle regulators such as the retinoblastoma protein. Since our current understanding of how redox regulation is involved in cell cycle control is hindered by a lack of knowledge regarding both which residues are important and how modification of those residues alters protein function, we discuss how critical redox modifications can be mapped at the molecular level. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Timing of developmental reduction in epithelial glutathione redox potential is associated with increased epithelial proliferation in the immature murine intestine.

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Reid, Graham K; Berardinelli, Andrew J; Ray, Laurie; Jackson, Arena R; Neish, Andrew S; Hansen, Jason M; Denning, Patricia W

2017-08-01

BackgroundThe intracellular redox potential of the glutathione (GSH)/glutathione disulfide (GSSG) couple regulates cellular processes. In vitro studies indicate that a reduced GSH/GSSG redox potential favors proliferation, whereas a more oxidized redox potential favors differentiation. Intestinal growth depends upon an appropriate balance between the two. However, how the ontogeny of intestinal epithelial cellular (IEC) GSH/GSSG redox regulates these processes in the developing intestine has not been fully characterized in vivo.MethodsOntogeny of intestinal GSH redox potential and growth were measured in neonatal mice.ResultsWe show that IEC GSH/GSSG redox potential becomes increasingly reduced (primarily driven by increased GSH concentration) over the first 3 weeks of life. Increased intracellular GSH has been shown to drive proliferation through increased poly-ADP-ribose polymerase (PARP) activity. We show that increasing IEC poly-ADP-ribose chains can be measured over the first 3 weeks of life, indicating an increase in IEC PARP activity. These changes are accompanied by increased intestinal growth and IEC proliferation as assessed by villus height/crypt depth, intestinal length, and Ki67 staining.ConclusionUnderstanding how IEC GSH/GSSG redox potential is developmentally regulated may provide insight into how premature human intestinal redox states can be manipulated to optimize intestinal growth and adaptation.

Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redox-sensitivity, and triggered intracellular drug release

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Omrani, Ismail; Babanejad, Niloofar; Shendi, Hasan Kashef; Nabid, Mohammad Reza, E-mail: m-nabid@sbu.ac.ir

2017-01-01

Polyurethanes are important class of biomaterials that are extensively used in medical devices. In spite of their easy synthesis, polyurethanes that are fully degradable in response to the intracellular reducing environment are less explored for controlled drug delivery. Herein, a novel glutathione degradable waterborne polyurethane (WPU) nanocarrier for redox triggered intracellular delivery of a model lipophilic anticancer drug, doxorubicin (DOX) is reported. The WPU was prepared from polyaddition reaction of isophorone diisocyanate (IPDI) and a novel linear polyester polyol involving disulfide linkage, disulfide labeled chain extender, dimethylolpropionic acid (DMPA) using dibutyltin dilaurate (DBTDL) as a catalyst. The resulting polyurethane self-assembles into nanocarrier in water. The dynamic light scattering (DLS) measurements and scanning electron microscope (SEM) revealed fast swelling and disruption of nanocarriers under an intracellular reduction-mimicking environment. The in vitro release studies showed that DOX was released in a controlled and redox-dependent manner. MTT assays showed that DOX-loaded WPU had a high in vitro antitumor activity in both HDF noncancer cells and MCF- 7 cancer cells. In addition, it is found that the blank WPU nanocarriers are nontoxic to HDF and MCF-7 cells even at a high concentration of 2 mg/mL. Hence, nanocarriers based on disulfide labeled WPU have appeared as a new class of biocompatible and redox-degradable nanovehicle for efficient intracellular drug delivery. - Highlights: • A novel fully glutathione degradable waterborne polyurethane was developed. • The waterborne nanocarrier with disulfide bonds in both hard and soft segment were developed for redox-triggered intracellular delivery of DOX. • The polyester diol bearing disulfide bonds in the backbone was prepared by a polycondensation polymerization reaction.

Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System.

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Ren, Xiaoyuan; Zou, Lili; Zhang, Xu; Branco, Vasco; Wang, Jun; Carvalho, Cristina; Holmgren, Arne; Lu, Jun

2017-11-01

The thioredoxin (Trx) and glutathione (GSH) systems play important roles in maintaining the redox balance in the brain, a tissue that is prone to oxidative stress due to its high-energy demand. These two disulfide reductase systems are active in various areas of the brain and are considered to be critical antioxidant systems in the central nervous system (CNS). Various neuronal disorders have been characterized to have imbalanced redox homeostasis. Recent Advances: In addition to their detrimental effects, recent studies have highlighted that reactive oxygen species/reactive nitrogen species (ROS/RNS) act as critical signaling molecules by modifying thiols in proteins. The Trx and GSH systems, which reversibly regulate thiol modifications, regulate redox signaling involved in various biological events in the CNS. In this review, we focus on the following: (i) how ROS/RNS are produced and mediate signaling in CNS; (ii) how Trx and GSH systems regulate redox signaling by catalyzing reversible thiol modifications; (iii) how dysfunction of the Trx and GSH systems causes alterations of cellular redox signaling in human neuronal diseases; and (iv) the effects of certain small molecules that target thiol-based signaling pathways in the CNS. Further study on the roles of thiol-dependent redox systems in the CNS will improve our understanding of the pathogenesis of many human neuronal disorders and also help to develop novel protective and therapeutic strategies against neuronal diseases. Antioxid. Redox Signal. 27, 989-1010.

Impact of uranium (U) on the cellular glutathione pool and resultant consequences for the redox status of U.

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Viehweger, Katrin; Geipel, Gerhard; Bernhard, Gert

2011-12-01

Uranium (U) as a redox-active heavy metal can cause various redox imbalances in plant cells. Measurements of the cellular glutathione/glutathione disulfide (GSH/GSSG) by HPLC after cellular U contact revealed an interference with this essential redox couple. The GSH content remained unaffected by 10 μM U whereas the GSSG level immediately increased. In contrast, higher U concentrations (50 μM) drastically raised both forms. Using the Nernst equation, it was possible to calculate the half-cell reduction potential of 2GSH/GSSG. In case of lower U contents the cellular redox environment shifted towards more oxidizing conditions whereas the opposite effect was obtained by higher U contents. This indicates that U contact causes a consumption of reduced redox equivalents. Artificial depletion of GSH by chlorodinitrobenzene and measuring the cellular reducing capacity by tetrazolium salt reduction underlined the strong requirement of reduced redox equivalents. An additional element of cellular U detoxification mechanisms is the complex formation between the heavy metal and carboxylic functionalities of GSH. Because two GSH molecules catalyze electron transfers each with one electron forming a dimer (GSSG) two UO(2) (2+) are reduced to each UO(2) (+) by unbound redox sensitive sulfhydryl moieties. UO(2) (+) subsequently disproportionates to UO(2) (2+) and U(4+). This explains that in vitro experiments revealed a reduction to U(IV) of only around 33% of initial U(VI). Cellular U(IV) was transiently detected with the highest level after 2 h of U contact. Hence, it can be proposed that these reducing processes are an important element of defense reactions induced by this heavy metal.

Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1

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Koji Aoyama

2015-05-01

Full Text Available Reactive oxygen species (ROS are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1 plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.

Effects of cisplatin on lipid peroxidation and the glutathione redox status in the liver of male rats: The protective role of selenium

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Trbojević Ivana S.

2010-01-01

Full Text Available The role of oxidative stress in cisplatin (CP toxicity and its prevention by pretreatment with selenium (Se was investigated. Male Wistar albino rats were injected with a single dose of cisplatin (7.5 mg CP/kg b.m., i.p. and selenium (6 mg Se/kg b.m, as Na2SeO3, i.p. alone or in combination. The results suggest that CP intoxication induces oxidative stress and alters the glutathione redox status: reduced glutathione (GSH, oxidized glutathione (GSSG and the GSH/GSSG ratio (GSH RI, resulting in increased lipid peroxidation (LPO in rat liver. The pretreatment with selenium prior to CP treatment showed a protective effect against the toxic influence of CP on peroxidation of the membrane lipids and an altering of the glutathione redox status in the liver of rats. From our results we conclude that selenium functions as a potent antioxidant and suggest that it can control CP-induced hepatotoxicity in rats.

Redox pioneer:Professor Christine Helen Foyer.

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Del Río, Luis A

2011-10-15

Dr. Christine Foyer (B.Sc. 1974; Ph.D. 1977) is recognized here as a Redox Pioneer because she has published an article on redox biology that has been cited more than 1000 times, 4 other articles that have been cited more than 500 times, and a further 32 articles that have been each cited more than 100 times. During her Ph.D. at the Kings College, University of London, United Kingdom, Dr. Foyer discovered that ascorbate and glutathione and enzymes linking NADPH, glutathione, and ascorbate are localized in isolated chloroplast preparations. These observations pioneered the discovery of the ascorbate-glutathione cycle, now known as Foyer-Halliwell-Asada pathway after the names of the three major contributors, a crucial mechanism for H(2)O(2) metabolism in both animals and plants. Dr. Foyer has made a very significant contribution to our current understanding of the crucial roles of ascorbate and glutathione in redox biology, particularly in relation to photosynthesis, respiration, and chloroplast and mitochondrial redox signaling networks. "My view is that science…is compulsive and you have to keep with it all the time and not get despondent when things do not work well. Being passionate about science is what carries you through the hard times so that it isn't so much work, as a hobby that you do for a living. It is the thrill of achieving a better understanding and finding real pleasure in putting new ideas together, explaining data and passing on knowledge that keeps you going no matter what!" --Prof. Christine Helen Foyer.

Glutathione in plants: an integrated overview.

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Noctor, Graham; Mhamdi, Amna; Chaouch, Sejir; Han, Yi; Neukermans, Jenny; Marquez-Garcia, Belen; Queval, Guillaume; Foyer, Christine H

2012-02-01

Plants cannot survive without glutathione (γ-glutamylcysteinylglycine) or γ-glutamylcysteine-containing homologues. The reasons why this small molecule is indispensable are not fully understood, but it can be inferred that glutathione has functions in plant development that cannot be performed by other thiols or antioxidants. The known functions of glutathione include roles in biosynthetic pathways, detoxification, antioxidant biochemistry and redox homeostasis. Glutathione can interact in multiple ways with proteins through thiol-disulphide exchange and related processes. Its strategic position between oxidants such as reactive oxygen species and cellular reductants makes the glutathione system perfectly configured for signalling functions. Recent years have witnessed considerable progress in understanding glutathione synthesis, degradation and transport, particularly in relation to cellular redox homeostasis and related signalling under optimal and stress conditions. Here we outline the key recent advances and discuss how alterations in glutathione status, such as those observed during stress, may participate in signal transduction cascades. The discussion highlights some of the issues surrounding the regulation of glutathione contents, the control of glutathione redox potential, and how the functions of glutathione and other thiols are integrated to fine-tune photorespiratory and respiratory metabolism and to modulate phytohormone signalling pathways through appropriate modification of sensitive protein cysteine residues. © 2011 Blackwell Publishing Ltd.

Brassinosteroid-induced CO2 assimilation is associated with increased stability of redox-sensitive photosynthetic enzymes in the chloroplasts in cucumber plants

International Nuclear Information System (INIS)

Jiang, Yu Ping; Cheng, Fei; Zhou, Yan Hong; Xia, Xiao Jian; Mao, Wei Hua; Shi, Kai; Chen, Zhi Xiang; Yu, Jing Quan

2012-01-01

Highlights: ► Activity of certain Calvin cycle enzymes and CO 2 assimilation are induced by BRs. ► BRs upregulate the activity of the ascorbate–glutathione cycle in the chloroplasts. ► BRs increase the chloroplast thiol reduction state. ► A BR-induced reducing environment increases the stability of photosynthetic enzymes. -- Abstract: Brassinosteroids (BRs) play important roles in plant growth, development, photosynthesis and stress tolerance; however, the mechanism underlying BR-enhanced photosynthesis is currently unclear. Here, we provide evidence that an increase in the BR level increased the quantum yield of PSII, activities of Rubisco activase (RCA) and fructose-1,6-bisphosphatase (FBPase), and CO 2 assimilation. BRs upregulated the transcript levels of genes and activity of enzymes involved in the ascorbate–glutathione cycle in the chloroplasts, leading to an increased ratio of reduced (GSH) to oxidized (GSSG) glutathione in the chloroplasts. An increased GSH/GSSG ratio protected RCA from proteolytic digestion and increased the stability of redox-sensitive enzymes in the chloroplasts. These results strongly suggest that BRs are capable of regulating the glutathione redox state in the chloroplasts through the activation of the ascorbate–glutathione cycle. The resulting increase in the chloroplast thiol reduction state promotes CO 2 assimilation, at least in part, by enhancing the stability and activity of redox-sensitive photosynthetic enzymes through post-translational modifications.

The Comparison of One-Session Intensive Aerobic Exercise Effects on Glutathione Redox State of Red Blood Cells in Professional, Recreational Athletes and Nonathletes

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Farnaz Seifi-Skishahr

2015-04-01

Full Text Available Background & objectives: The “redox” state represents the oxidation/reduction potential within the cell in a way that more “redox” is the marker of health, while the more oxidized reflects predisposition to diseases. Different types of exercise training may change the thiol/disulfide ratio of redox couples such as glutathione and represent a shift in redox balance. This study was assessed the influence of high-intensity aerobic exercise on glutathione redox state in red blood cells in professional, recreational athletes and nonathletes.   Methods: Ten voluntary well trained (WT, moderately trained (MT and untrained men subjectswere randomly selected for this semi-experimental study (mean ages of 21.10±1.72 21.70±1.88 and 20.10±1.44, respectively. Blood samples were collected before, immediately, 10 min and 30 min after acute aerobic exercise with 75%VO2max. The levels of reduced glutathione (GSH, oxidized glutathione (GSSG and (GSH/GSSG in red blood cells (RBCs as well as serum levels of cortisol and creatine kinase (CK were measured.   Results: The results showed reduction, elevation and no changes in RBCs GSH/GSSG ratio in UT, MT and WT groups, respectively. The lowest levels of GSH/GSSG ratio in RBCs and the highest one were detected in the WT and MT groups, respectively. The serum levels of cortisol and creatine kinase were increased following the exercise in three groups.   Conclusion: It is concluded that acute aerobic exercise with high intensity does not change redox balance in well trained subjects, however it is capable to shift redox balance towards more reducing environment in moderately trained subjects and also to more oxidizing one in untrained subjects.

A nuclear glutathione cycle within the cell cycle.

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Diaz Vivancos, Pedro; Wolff, Tonja; Markovic, Jelena; Pallardó, Federico V; Foyer, Christine H

2010-10-15

The complex antioxidant network of plant and animal cells has the thiol tripeptide GSH at its centre to buffer ROS (reactive oxygen species) and facilitate cellular redox signalling which controls growth, development and defence. GSH is found in nearly every compartment of the cell, including the nucleus. Transport between the different intracellular compartments is pivotal to the regulation of cell proliferation. GSH co-localizes with nuclear DNA at the early stages of proliferation in plant and animal cells. Moreover, GSH recruitment and sequestration in the nucleus during the G1- and S-phases of the cell cycle has a profound impact on cellular redox homoeostasis and on gene expression. For example, the abundance of transcripts encoding stress and defence proteins is decreased when GSH is sequestered in the nucleus. The functions of GSHn (nuclear GSH) are considered in the present review in the context of whole-cell redox homoeostasis and signalling, as well as potential mechanisms for GSH transport into the nucleus. We also discuss the possible role of GSHn as a regulator of nuclear proteins such as histones and PARP [poly(ADP-ribose) polymerase] that control genetic and epigenetic events. In this way, a high level of GSH in the nucleus may not only have an immediate effect on gene expression patterns, but also contribute to how cells retain a memory of the cellular redox environment that is transferred through generations.

In Vivo Monitoring of pH, Redox Status, and Glutathione Using L-Band EPR for Assessment of Therapeutic Effectiveness in Solid Tumors

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Bobko, Andrey A.; Eubank, Timothy D.; Voorhees, Jeffrey L.; Efimova, Olga V.; Kirilyuk, Igor A.; Petryakov, Sergey; Trofimiov, Dmitrii G.; Marsh, Clay B.; Zweier, Jay L.; Grigor’ev, Igor A.; Samouilov, Alexandre; Khramtsov, Valery V.

2011-01-01

Approach for in vivo real-time assessment of tumor tissue extracellular pH (pHe), redox, and intracellular glutathione based on L-band EPR spectroscopy using dual function pH and redox nitroxide probe and disulfide nitroxide biradical, is described. These parameters were monitored in PyMT mice bearing breast cancer tumors during treatment with granulocyte macrophage colony-stimulating factor. It was observed that tumor pHe is about 0.4 pH units lower than that in normal mammary gland tissue. Treatment with granulocyte macrophage colony-stimulating factor decreased the value of pHe by 0.3 units compared with PBS control treatment. Tumor tissue reducing capacity and intracellular glutathione were elevated compared with normal mammary gland tissue. Granulocyte macrophage colony-stimulating factor treatment resulted in a decrease of the tumor tissue reducing capacity and intracellular glutathione content. In addition to spectroscopic studies, pHe mapping was performed using recently proposed variable frequency proton–electron double-resonance imaging. The pH mapping superimposed with MRI image supports probe localization in mammary gland/tumor tissue, shows high heterogeneity of tumor tissue pHe and a difference of about 0.4 pH units between average pHe values in tumor and normal mammary gland. In summary, the developed multifunctional approach allows for in vivo, noninvasive pHe, extracellular redox, and intracellular glutathione content monitoring during investigation of various therapeutic strategies for solid tumors. Magn Reson Med 000:000–000, 2011. PMID:22113626

Redox regulation of the Calvin-Benson cycle: something old, something new

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Laure eMichelet

2013-11-01

Full Text Available Reversible redox post-translational modifications such as oxido-reduction of disulfide bonds, S-nitrosylation and S-glutathionylation, play a prominent role in the regulation of cell metabolism and signaling in all organisms. These modifications are mainly controlled by members of the thioredoxin and glutaredoxin families. Early studies in photosynthetic organisms have identified the Calvin-Benson cycle, the photosynthetic pathway responsible for carbon assimilation, as a redox regulated process. Indeed, 4 out of 11 enzymes of the cycle were shown to have a low activity in the dark and to be activated in the light through thioredoxin-dependent reduction of regulatory disulfide bonds. The underlying molecular mechanisms were extensively studied at the biochemical and structural level. Unexpectedly, recent biochemical and proteomic studies have suggested that all enzymes of the cycle and several associated regulatory proteins may undergo redox regulation through multiple redox post-translational modifications including glutathionylation and nitrosylation. The aim of this review is to detail the well-established mechanisms of redox regulation of Calvin-Benson cycle enzymes as well as the most recent reports indicating that this pathway is tightly controlled by multiple interconnected redox post-translational modifications. This redox control is likely allowing fine tuning of the Calvin-Benson cycle required for adaptation to varying environmental conditions, especially during responses to biotic and abiotic stresses.

Silymarin protects PBMC against B(a)P induced toxicity by replenishing redox status and modulating glutathione metabolizing enzymes-An in vitro study

International Nuclear Information System (INIS)

Kiruthiga, P.V.; Pandian, S. Karutha; Devi, K. Pandima

2010-01-01

PAHs are a ubiquitous class of environmental contaminants that have a large number of hazardous consequences on human health. An important prototype of PAHs, B(a)P, is notable for being the first chemical carcinogen to be discovered and the one classified by EPA as a probable human carcinogen. It undergoes metabolic activation to QD, which generate ROS by redox cycling system in the body and oxidatively damage the macromolecules. Hence, a variety of antioxidants have been tested as possible protectors against B(a)P toxicity. Silymarin is one such compound, which has high human acceptance, used clinically and consumed as dietary supplement around the world for its strong anti-oxidant efficacy. Silymarin was employed as an alternative approach for treating B(a)P induced damage and oxidative stress in PBMC, with an emphasis to provide the molecular basis for the effect of silymarin against B(a)P induced toxicity. PBMC cells exposed to either benzopyrene (1 μM) or silymarin (2.4 mg/ml) or both was monitored for toxicity by assessing LPO, PO, redox status (GSH/GSSG ratio), glutathione metabolizing enzymes GR and GPx and antioxidant enzymes CAT and SOD. This study also investigated the protective effect of silymarin against B(a)P induced biochemical alteration at the molecular level by FT-IR spectroscopy. Our findings were quite striking that silymarin possesses substantial protective effect against B(a)P induced oxidative stress and biochemical changes by restoring redox status, modulating glutathione metabolizing enzymes, hindering the formation of protein oxidation products, inhibiting LPO and further reducing ROS mediated damages by changing the level of antioxidant enzymes. The results suggest that silymarin exhibits multiple protections and it should be considered as a potential protective agent for environmental contaminant induced immunotoxicity.

Dimensional behavior of Ni-YSZ composites during redox cycling

DEFF Research Database (Denmark)

Pihlatie, Mikko; Kaiser, Andreas; Larsen, Peter Halvor

2009-01-01

The dimensional behavior of Ni-yttria-stabilized zirconia (YSZ) cermets during redox cycling was tested in dilatometry within the temperature range 600-1000 degrees C. The effect Of humidity oil redox stability was investigated at intermediate and low temperatures. We show that both the sintering...... of nickel depending on temperature of the initial reduction and the operating conditions, and the temperature of reoxidation are very important for the size of the dimensional change. Cumulative redox strain (CRS) is shown to be correlated with temperature. Measured maximum CRS after three redox cycles...... varies within 0.25-3.2% dL/L in dry gas and respective temperature range of 600-1000 degrees C. A high degree of redox reversibility was reached at low temperature. however. reversibility is lost at elevated temperatures. We found that at 850 degrees C, 6% steam and a very high p(H2O)/p(H2) ratio...

Recruitment of glutathione into the nucleus during cell proliferation adjusts whole-cell redox homeostasis in Arabidopsis thaliana and lowers the oxidative defence shield.

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Vivancos, Pedro Diaz; Dong, Yingping; Ziegler, Kerstin; Markovic, Jelena; Pallardó, Federico V; Pellny, Till K; Verrier, Paul J; Foyer, Christine H

2010-12-01

Cellular redox homeostasis and signalling are important in progression of the eukaryotic cell cycle. In animals, the low-molecular-weight thiol tripeptide glutathione (GSH) is recruited into the nucleus early in the cell proliferation cycle. To determine whether a similar process occurs in plants, we studied cell proliferation in Arabidopsis thaliana. We show that GSH co-localizes with nuclear DNA during the proliferation of A. thaliana cells in culture. Moreover, GSH localization in the nucleus was observed in dividing pericycle cells of the lateral root meristem. There was pronounced accumulation of GSH in the nucleus at points in the growth cycle at which a high percentage of the cells were in G(1) phase, as identified by flow cytometry and marker transcripts. Recruitment of GSH into the nucleus led to a high abundance of GSH in the nucleus (GSHn) and severe depletion of the cytoplasmic GSH pool (GSHc). Sequestration of GSH in the nucleus was accompanied by significant decreases in transcripts associated with oxidative signalling and stress tolerance, and an increase in the abundance of hydrogen peroxide, an effect that was enhanced when the dividing cells were treated with salicylic acid. Total cellular GSH and the abundance of GSH1 and GSH2 transcripts increased after the initial recruitment of GSH into the nucleus. We conclude that GSH recruitment into the nucleus during cell proliferation has a profound effect on the whole-cell redox state. High GSHn levels trigger redox adjustments in the cytoplasm, favouring decreased oxidative signalling and enhanced GSH synthesis. © 2010 The Authors. The Plant Journal © 2010 Blackwell Publishing Ltd.

Redox Couples with Unequal Diffusion Coefficients: Effect on Redox Cycling

NARCIS (Netherlands)

Mampallil Augustine, Dileep; Mathwig, Klaus; Kang, Shuo; Lemay, Serge Joseph Guy

2013-01-01

Redox cycling between two electrodes separated by a narrow gap allows dramatic amplification of the faradaic current. Unlike conventional electrochemistry at a single electrode, however, the mass-transport-limited current is controlled by the diffusion coefficient of both the reduced and oxidized

Brassinosteroid-induced CO{sub 2} assimilation is associated with increased stability of redox-sensitive photosynthetic enzymes in the chloroplasts in cucumber plants

Energy Technology Data Exchange (ETDEWEB)

Jiang, Yu Ping; Cheng, Fei; Zhou, Yan Hong; Xia, Xiao Jian; Mao, Wei Hua; Shi, Kai [Department of Horticulture, Zijingang Campus, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058 (China); Chen, Zhi Xiang [Department of Horticulture, Zijingang Campus, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058 (China); Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907-2054 (United States); Yu, Jing Quan, E-mail: jqyu@zju.edu.cn [Department of Horticulture, Zijingang Campus, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058 (China); Key Laboratory of Horticultural Plants Growth, Development and Quality Improvement, Ministry of Agriculture of China, Yuhangtang Road 866, Hangzhou 310058 (China)

2012-09-28

Highlights: Black-Right-Pointing-Pointer Activity of certain Calvin cycle enzymes and CO{sub 2} assimilation are induced by BRs. Black-Right-Pointing-Pointer BRs upregulate the activity of the ascorbate-glutathione cycle in the chloroplasts. Black-Right-Pointing-Pointer BRs increase the chloroplast thiol reduction state. Black-Right-Pointing-Pointer A BR-induced reducing environment increases the stability of photosynthetic enzymes. -- Abstract: Brassinosteroids (BRs) play important roles in plant growth, development, photosynthesis and stress tolerance; however, the mechanism underlying BR-enhanced photosynthesis is currently unclear. Here, we provide evidence that an increase in the BR level increased the quantum yield of PSII, activities of Rubisco activase (RCA) and fructose-1,6-bisphosphatase (FBPase), and CO{sub 2} assimilation. BRs upregulated the transcript levels of genes and activity of enzymes involved in the ascorbate-glutathione cycle in the chloroplasts, leading to an increased ratio of reduced (GSH) to oxidized (GSSG) glutathione in the chloroplasts. An increased GSH/GSSG ratio protected RCA from proteolytic digestion and increased the stability of redox-sensitive enzymes in the chloroplasts. These results strongly suggest that BRs are capable of regulating the glutathione redox state in the chloroplasts through the activation of the ascorbate-glutathione cycle. The resulting increase in the chloroplast thiol reduction state promotes CO{sub 2} assimilation, at least in part, by enhancing the stability and activity of redox-sensitive photosynthetic enzymes through post-translational modifications.

Contribution of Fdh3 and Glr1 to Glutathione Redox State, Stress Adaptation and Virulence in Candida albicans.

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Anna T Tillmann

Full Text Available The major fungal pathogen of humans, Candida albicans, is exposed to reactive nitrogen and oxygen species following phagocytosis by host immune cells. In response to these toxins, this fungus activates potent anti-stress responses that include scavenging of reactive nitrosative and oxidative species via the glutathione system. Here we examine the differential roles of two glutathione recycling enzymes in redox homeostasis, stress adaptation and virulence in C. albicans: glutathione reductase (Glr1 and the S-nitrosoglutathione reductase (GSNOR, Fdh3. We show that the NADPH-dependent Glr1 recycles GSSG to GSH, is induced in response to oxidative stress and is required for resistance to macrophage killing. GLR1 deletion increases the sensitivity of C. albicans cells to H2O2, but not to formaldehyde or NO. In contrast, Fdh3 detoxifies GSNO to GSSG and NH3, and FDH3 inactivation delays NO adaptation and increases NO sensitivity. C. albicans fdh3⎔ cells are also sensitive to formaldehyde, suggesting that Fdh3 also contributes to formaldehyde detoxification. FDH3 is induced in response to nitrosative, oxidative and formaldehyde stress, and fdh3Δ cells are more sensitive to killing by macrophages. Both Glr1 and Fdh3 contribute to virulence in the Galleria mellonella and mouse models of systemic infection. We conclude that Glr1 and Fdh3 play differential roles during the adaptation of C. albicans cells to oxidative, nitrosative and formaldehyde stress, and hence during the colonisation of the host. Our findings emphasise the importance of the glutathione system and the maintenance of intracellular redox homeostasis in this major pathogen.

TEMPOL increases NAD+ and improves redox imbalance in obese mice

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Mayumi Yamato

2016-08-01

Full Text Available Continuous energy conversion is controlled by reduction–oxidation (redox processes. NAD+ and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS and is reduced to hydroxylamine by NADH. TEMPOL is also involved in NAD+ production in the ascorbic acid–glutathione redox cycle. We utilized the chemical properties of TEMPOL to investigate the effects of antioxidants and NAD+/NADH modulators on the metabolic imbalance in obese mice. Increases in the NAD+/NADH ratio by TEMPOL ameliorated the metabolic imbalance when combined with a dietary intervention, changing from a high-fat diet to a normal diet. Plasma levels of the superoxide marker dihydroethidium were higher in mice receiving the dietary intervention compared with a control diet, but were normalized with TEMPOL consumption. These findings provide novel insights into redox regulation in obesity.

Redox Cycling Realized in Paper-Based Biochemical Sensor for Selective Detection of Reversible Redox Molecules Without Micro/Nano Fabrication Process.

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Yamamoto, So; Uno, Shigeyasu

2018-02-28

This paper describes a paper-based biochemical sensor that realizes redox cycling with close interelectrode distance. Two electrodes, the generator and collector electrodes, can detect steady-state oxidation and reduction currents when suitable potential is held at each electrode. The sensor has two gold plates on both sides of a piece of chromatography paper and defines the interelectrode distance by the thickness of the paper (180 μm) without any micro-fabrication processes. Our proposed sensor geometry has successfully exhibited signatures of redox cycling. As a result, the concentration of ferrocyanide as reversible redox molecules was successfully quantified under the interference by ascorbic acid as a strong irreversible reducing agent. This was possible because the ascorbic acids are completely consumed by the irreversible reaction, while maintaining redox cycling of reversible ferrocyanide. This suggests that a sensor based on the redox cycling method will be suitable for detecting target molecules at low concentration.

Redox cycling of potential antitumor aziridinylquinones

NARCIS (Netherlands)

Lusthof, Klaas J.; de Mol, Nicolaas J.; Richter, Wilma; Janssen, Lambert H.M.; Butler, John; Hoey, Brigid M.; Verboom, Willem; Reinhoudt, David

1992-01-01

The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthetized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase

Redox Changes During the Cell Cycle in the Embryonic Root Meristem of Arabidopsis thaliana.

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de Simone, Ambra; Hubbard, Rachel; de la Torre, Natanael Viñegra; Velappan, Yazhini; Wilson, Michael; Considine, Michael J; Soppe, Wim J J; Foyer, Christine H

2017-12-20

The aim of this study was to characterize redox changes in the nuclei and cytosol occurring during the mitotic cell cycle in the embryonic roots of germinating Arabidopsis seedlings, and to determine how redox cycling was modified in mutants with a decreased capacity for ascorbate synthesis. Using an in vivo reduction-oxidation (redox) reporter (roGFP2), we show that transient oxidation of the cytosol and the nuclei occurred at G1 in the synchronized dividing cells of the Arabidopsis root apical meristem, with reduction at G2 and mitosis. This redox cycle was absent from low ascorbate mutants in which nuclei were significantly more oxidized than controls. The cell cycle-dependent increase in nuclear size was impaired in the ascorbate-deficient mutants, which had fewer cells per unit area in the root proliferation zone. The transcript profile of the dry seeds and size of the imbibed seeds was strongly influenced by low ascorbate but germination, dormancy release and seed aging characteristics were unaffected. These data demonstrate the presence of a redox cycle within the plant cell cycle and that the redox state of the nuclei is an important factor in cell cycle progression. Controlled oxidation is a key feature of the early stages of the plant cell cycle. However, sustained mild oxidation restricts nuclear functions and impairs progression through the cell cycle leading to fewer cells in the root apical meristem. Antioxid. Redox Signal. 27, 1505-1519.

The antioxidant master glutathione and periodontal health

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Vivek Kumar Bains

2015-01-01

Full Text Available Glutathione, considered to be the master antioxidant (AO, is the most-important redox regulator that controls inflammatory processes, and thus damage to the periodontium. Periodontitis patients have reduced total AO capacity in whole saliva, and lower concentrations of reduced glutathione (GSH in serum and gingival crevicular fluid, and periodontal therapy restores the redox balance. Therapeutic considerations for the adjunctive use of glutathione in management of periodontitis, in limiting the tissue damage associated with oxidative stress, and enhancing wound healing cannot be underestimated, but need to be evaluated further through multi-centered randomized controlled trials.

The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?

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Deponte, Marcel

2017-11-20

Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids, and iron-sulfur clusters. In addition, glutathione affects oxidative protein folding and redox signaling. Here, I try to provide an overview on the relevance of glutathione-dependent pathways with an emphasis on quantitative data. Recent Advances: Intracellular redox measurements reveal that the cytosol, the nucleus, and mitochondria contain very little glutathione disulfide and that oxidative challenges are rapidly counterbalanced. Genetic approaches suggest that iron metabolism is the centerpiece of the glutathione puzzle in yeast. Furthermore, recent biochemical studies provide novel insights on glutathione transport processes and uncoupling mechanisms. Which parts of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can iron-sulfur cluster biogenesis, oxidative protein folding, or redox signaling occur at high glutathione concentrations? Answers to these questions not only seem to depend on the organism, cell type, and subcellular compartment but also on different ideologies among researchers. A rational approach to compare the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, there are still many missing pieces and too little is known about the compartment-specific repertoire and concentration of numerous metabolites, substrates, enzymes, and transporters as well as rate constants and enzyme kinetic patterns. Gathering this information might require the development of novel tools but is crucial to address potential kinetic competitions and to decipher uncoupling mechanisms to solve the glutathione puzzle. Antioxid. Redox Signal

Endoplasmic reticulum transport of glutathione by Sec61 is regulated by Ero1 and Bip

DEFF Research Database (Denmark)

Ponsero, Alise J.; Igbaria, Aeid; Darch, Maxwell A.

2017-01-01

In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative...... oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import...... by reduction, causing Bip oxidation and inhibition of glutathione transport. Coupling of glutathione ER import to Ero1 activation provides a basis for glutathione ER redox poise maintenance....

Redox regulation of photosynthetic gene expression.

Science.gov (United States)

Queval, Guillaume; Foyer, Christine H

2012-12-19

Redox chemistry and redox regulation are central to the operation of photosynthesis and respiration. However, the roles of different oxidants and antioxidants in the regulation of photosynthetic or respiratory gene expression remain poorly understood. Leaf transcriptome profiles of a range of Arabidopsis thaliana genotypes that are deficient in either hydrogen peroxide processing enzymes or in low molecular weight antioxidant were therefore compared to determine how different antioxidant systems that process hydrogen peroxide influence transcripts encoding proteins targeted to the chloroplasts or mitochondria. Less than 10 per cent overlap was observed in the transcriptome patterns of leaves that are deficient in either photorespiratory (catalase (cat)2) or chloroplastic (thylakoid ascorbate peroxidase (tapx)) hydrogen peroxide processing. Transcripts encoding photosystem II (PSII) repair cycle components were lower in glutathione-deficient leaves, as were the thylakoid NAD(P)H (nicotinamide adenine dinucleotide (phosphate)) dehydrogenases (NDH) mRNAs. Some thylakoid NDH mRNAs were also less abundant in tAPX-deficient and ascorbate-deficient leaves. Transcripts encoding the external and internal respiratory NDHs were increased by low glutathione and low ascorbate. Regulation of transcripts encoding specific components of the photosynthetic and respiratory electron transport chains by hydrogen peroxide, ascorbate and glutathione may serve to balance non-cyclic and cyclic electron flow pathways in relation to oxidant production and reductant availability.

The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis

Science.gov (United States)

2012-01-01

Background Glutathione has a wide range of functions; it is an endogenous anti-oxidant and plays a key role in the maintenance of intracellular redox balance and detoxification of xenobiotics. Several studies have indicated that children with autism spectrum disorders may have altered glutathione metabolism which could play a key role in the condition. Methods A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or genes of the glutathione metabolism pathways i.e. the γ-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders. Results Thirty nine studies were included in the review comprising an in vitro study, thirty two metabolite and/or co-factor studies, six intervention studies and six studies with genetic data as well as eight studies examining enzyme activity. Conclusions The review found evidence for the involvement of the γ-glutamyl cycle and trans-sulphuration pathway in autistic disorder is sufficiently consistent, particularly with respect to the glutathione redox ratio, to warrant further investigation to determine the significance in relation to clinical outcomes. Large, well designed intervention studies that link metabolites, cofactors and genes of the γ-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes in children with autism spectrum disorders are required. Future risk factor analysis should include consideration of multiple nutritional status and metabolite biomarkers of pathways linked with the γ-glutamyl cycle and the interaction of genotype in relation to these factors. PMID:22524510

Redox regulation of plant development.

Science.gov (United States)

Considine, Michael J; Foyer, Christine H

2014-09-20

We provide a conceptual framework for the interactions between the cellular redox signaling hub and the phytohormone signaling network that controls plant growth and development to maximize plant productivity under stress-free situations, while limiting growth and altering development on exposure to stress. Enhanced cellular oxidation plays a key role in the regulation of plant growth and stress responses. Oxidative signals or cycles of oxidation and reduction are crucial for the alleviation of dormancy and quiescence, activating the cell cycle and triggering genetic and epigenetic control that underpin growth and differentiation responses to changing environmental conditions. The redox signaling hub interfaces directly with the phytohormone network in the synergistic control of growth and its modulation in response to environmental stress, but a few components have been identified. Accumulating evidence points to a complex interplay of phytohormone and redox controls that operate at multiple levels. For simplicity, we focus here on redox-dependent processes that control root growth and development and bud burst. The multiple roles of reactive oxygen species in the control of plant growth and development have been identified, but increasing emphasis should now be placed on the functions of redox-regulated proteins, along with the central roles of reductants such as NAD(P)H, thioredoxins, glutathione, glutaredoxins, peroxiredoxins, ascorbate, and reduced ferredoxin in the regulation of the genetic and epigenetic factors that modulate the growth and vigor of crop plants, particularly within an agricultural context.

NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic β-cells

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Laila R.B. Santos

2017-06-01

Full Text Available Objective: The glucose stimulation of insulin secretion (GSIS by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca2+ influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets. Methods: Islets were isolated from female C57BL/6J mice (J-islets, which lack functional NNT, and genetically close C57BL/6N mice (N-islets. Wild-type mouse NNT was expressed in J-islets by adenoviral infection. Mitochondrial and cytosolic glutathione oxidation was measured with glutaredoxin 1-fused roGFP2 probes targeted or not to the mitochondrial matrix. NADPH and NADH redox state was measured biochemically. Insulin secretion and upstream coupling events were measured under dynamic or static conditions by standard procedures. Results: NNT is largely responsible for the acute glucose-induced rise in islet NADPH/NADP+ ratio and decrease in mitochondrial glutathione oxidation, with a small impact on cytosolic glutathione. However, contrary to current views on NNT in β-cells, these effects resulted from a glucose-dependent reduction in NADPH consumption by NNT reverse mode of operation, rather than from a stimulation of its forward mode of operation. Accordingly, the lack of NNT in J-islets decreased their sensitivity to exogenous H2O2 at non-stimulating glucose. Surprisingly, the lack of NNT did not alter the glucose-stimulation of Ca2+ influx and upstream mitochondrial events, but it markedly reduced both phases of GSIS by altering Ca2+-induced exocytosis and its metabolic amplification. Conclusion: These

Higher Mediterranean Diet Quality Scores and Lower Body Mass Index Are Associated with a Less-Oxidized Plasma Glutathione and Cysteine Redox Status in Adults.

Science.gov (United States)

Bettermann, Erika L; Hartman, Terryl J; Easley, Kirk A; Ferranti, Erin P; Jones, Dean P; Quyyumi, Arshed A; Vaccarino, Viola; Ziegler, Thomas R; Alvarez, Jessica A

2018-02-01

Both systemic redox status and diet quality are associated with risk outcomes in chronic disease. It is not known, however, the extent to which diet quality influences plasma thiol/disulfide redox status. The purpose of this study was to investigate the influence of diet, as measured by diet quality scores and other dietary factors, on systemic thiol/disulfide redox status. We performed a cross-sectional study of 685 working men and women (ages ≥18 y) in Atlanta, GA. Diet was assessed by 3 diet quality scores: the Alternative Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean Diet Score (MDS). We measured concentrations of plasma glutathione (GSH), cysteine, their associated oxidized forms [glutathione disulfide (GSSG) and cystine (CySS), respectively], and their redox potentials (EhGSSG and EhCySS) to determine thiol/disulfide redox status. Linear regression modeling was performed to assess relations between diet and plasma redox after adjustment for age, body mass index (BMI), sex, race, and history of chronic disease. MDS was positively associated with plasma GSH (β = 0.02; 95% CI: 0.003, 0.03) and total GSH (GSH + GSSG) (β = 0.02; 95% CI: 0.003, 0.03), and inversely associated with the CySS:GSH ratio (β = -0.02; 95% CI: -0.04, -0.004). There were significant independent associations between individual MDS components (dairy, vegetables, fish, and monounsaturated fat intake) and varying plasma redox indexes (P indexes and other diet factors of interest were not significantly correlated with plasma thiol and disulfide redox measures. Adherence to the Mediterranean diet was significantly associated with a favorable plasma thiol/disulfide redox profile, independent of BMI, in a generally healthy working adult population. Although longitudinal studies are warranted, these findings contribute to the feasibility of targeting a Mediterranean diet to improve plasma redox status.

Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths

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Salinas Gustavo

2010-04-01

Full Text Available Abstract Background The thioredoxin and/or glutathione pathways occur in all organisms. They provide electrons for deoxyribonucleotide synthesis, function as antioxidant defenses, in detoxification, Fe/S biogenesis and participate in a variety of cellular processes. In contrast to their mammalian hosts, platyhelminth (flatworm parasites studied so far, lack conventional thioredoxin and glutathione systems. Instead, they possess a linked thioredoxin-glutathione system with the selenocysteine-containing enzyme thioredoxin glutathione reductase (TGR as the single redox hub that controls the overall redox homeostasis. TGR has been recently validated as a drug target for schistosomiasis and new drug leads targeting TGR have recently been identified for these platyhelminth infections that affect more than 200 million people and for which a single drug is currently available. Little is known regarding the genomic structure of flatworm TGRs, the expression of TGR variants and whether the absence of conventional thioredoxin and glutathione systems is a signature of the entire platyhelminth phylum. Results We examine platyhelminth genomes and transcriptomes and find that all platyhelminth parasites (from classes Cestoda and Trematoda conform to a biochemical scenario involving, exclusively, a selenium-dependent linked thioredoxin-glutathione system having TGR as a central redox hub. In contrast, the free-living platyhelminth Schmidtea mediterranea (Class Turbellaria possesses conventional and linked thioredoxin and glutathione systems. We identify TGR variants in Schistosoma spp. derived from a single gene, and demonstrate their expression. We also provide experimental evidence that alternative initiation of transcription and alternative transcript processing contribute to the generation of TGR variants in platyhelminth parasites. Conclusions Our results indicate that thioredoxin and glutathione pathways differ in parasitic and free-living flatworms and

Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths

Science.gov (United States)

2010-01-01

Background The thioredoxin and/or glutathione pathways occur in all organisms. They provide electrons for deoxyribonucleotide synthesis, function as antioxidant defenses, in detoxification, Fe/S biogenesis and participate in a variety of cellular processes. In contrast to their mammalian hosts, platyhelminth (flatworm) parasites studied so far, lack conventional thioredoxin and glutathione systems. Instead, they possess a linked thioredoxin-glutathione system with the selenocysteine-containing enzyme thioredoxin glutathione reductase (TGR) as the single redox hub that controls the overall redox homeostasis. TGR has been recently validated as a drug target for schistosomiasis and new drug leads targeting TGR have recently been identified for these platyhelminth infections that affect more than 200 million people and for which a single drug is currently available. Little is known regarding the genomic structure of flatworm TGRs, the expression of TGR variants and whether the absence of conventional thioredoxin and glutathione systems is a signature of the entire platyhelminth phylum. Results We examine platyhelminth genomes and transcriptomes and find that all platyhelminth parasites (from classes Cestoda and Trematoda) conform to a biochemical scenario involving, exclusively, a selenium-dependent linked thioredoxin-glutathione system having TGR as a central redox hub. In contrast, the free-living platyhelminth Schmidtea mediterranea (Class Turbellaria) possesses conventional and linked thioredoxin and glutathione systems. We identify TGR variants in Schistosoma spp. derived from a single gene, and demonstrate their expression. We also provide experimental evidence that alternative initiation of transcription and alternative transcript processing contribute to the generation of TGR variants in platyhelminth parasites. Conclusions Our results indicate that thioredoxin and glutathione pathways differ in parasitic and free-living flatworms and that canonical enzymes

Novel roles of folic acid as redox regulator: Modulation of reactive oxygen species sinker protein expression and maintenance of mitochondrial redox homeostasis on hepatocellular carcinoma.

Science.gov (United States)

Lai, Kun-Goung; Chen, Chi-Fen; Ho, Chun-Te; Liu, Jun-Jen; Liu, Tsan-Zon; Chern, Chi-Liang

2017-06-01

We provide herein several lines of evidence to substantiate that folic acid (or folate) is a micronutrient capable of functioning as a novel redox regulator on hepatocellular carcinoma. First, we uncovered that folate deficiency could profoundly downregulate two prominent anti-apoptotic effectors including survivin and glucose-regulated protein-78. Silencing of either survivin or glucose-regulated protein-78 via small interfering RNA interfering technique established that both effectors could serve as reactive oxygen species sinker proteins. Second, folate deficiency-triggered oxidative-nitrosative stress could strongly induce endoplasmic reticulum stress that in turn could provoke cellular glutathione depletion through the modulation of the following two crucial events: (1) folate deficiency could strongly inhibit Bcl-2 expression leading to severe suppression of the mitochondrial glutathione pool and (2) folate deficiency could also profoundly inhibit two key enzymes that governing cellular glutathione redox regulation including γ-glutamylcysteinyl synthetase heavy chain, a catalytic enzyme for glutathione biosynthesis, and mitochondrial isocitrate dehydrogenase 2, an enzyme responsible for providing nicotinamide adenine dinucleotide phosphate necessary for regenerating oxidized glutathione disulfide back to glutathione via mitochondrial glutathione reductase. Collectively, we add to the literature new data to strengthen the notion that folate is an essential micronutrient that confers a novel role to combat reactive oxygen species insults and thus serves as a redox regulator via upregulating reactive oxygen species sinker proteins and averting mitochondrial glutathione depletion through proper maintenance of redox homeostasis via positively regulating glutathione biosynthesis, glutathione transporting system, and mitochondrial glutathione recycling process.

TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State.

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Cardaci, Simone; Ciriolo, Maria Rosa

2012-01-01

Inborn defects of the tricarboxylic acid (TCA) cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State

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Simone Cardaci

2012-01-01

Full Text Available Inborn defects of the tricarboxylic acid (TCA cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH, fumarate hydratase (FH, and isocitrate dehydrogenase (IDH, pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

Glutathione S-transferase P influences redox and migration pathways in bone marrow.

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Jie Zhang

Full Text Available To interrogate why redox homeostasis and glutathione S-transferase P (GSTP are important in regulating bone marrow cell proliferation and migration, we isolated crude bone marrow, lineage negative and bone marrow derived-dendritic cells (BMDDCs from both wild type (WT and knockout (Gstp1/p2(-/- mice. Comparison of the two strains showed distinct thiol expression patterns. WT had higher baseline and reactive oxygen species-induced levels of S-glutathionylated proteins, some of which (sarco-endoplasmic reticulum Ca2(+-ATPase regulate Ca(2+ fluxes and subsequently influence proliferation and migration. Redox status is also a crucial determinant in the regulation of the chemokine system. CXCL12 chemotactic response was stronger in WT cells, with commensurate alterations in plasma membrane polarization/permeability and intracellular calcium fluxes; activities of the downstream kinases, ERK and Akt were also higher in WT. In addition, expression levels of the chemokine receptor CXCR4 and its associated phosphatase, SHP-2, were higher in WT. Inhibition of CXCR4 or SHP2 decreased the extent of CXCL12-induced migration in WT BMDDCs. The differential surface densities of CXCR4, SHP-2 and inositol trisphosphate receptor in WT and Gstp1/p2(-/- cells correlated with the differential CXCR4 functional activities, as measured by the extent of chemokine-induced directional migration and differences in intracellular signaling. These observed differences contribute to our understanding of how genetic ablation of GSTP causes different levels of myeloproliferation and migration [corrected

Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic Cycle and Repairing of Disulfide Bonds in Scrambled Protein.

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Shimodaira, Shingo; Asano, Yuki; Arai, Kenta; Iwaoka, Michio

2017-10-24

Selenoglutathione (GSeH) is a selenium analogue of naturally abundant glutathione (GSH). In this study, this water-soluble small tripeptide was synthesized in a high yield (up to 98%) as an oxidized diselenide form, i.e., GSeSeG (1), by liquid-phase peptide synthesis (LPPS). Obtained 1 was applied to the investigation of the glutathione peroxidase (GPx)-like catalytic cycle. The important intermediates, i.e., GSe - and GSeSG, besides GSeO 2 H were characterized by 77 Se NMR spectroscopy. Thiol exchange of GSeSG with various thiols, such as cysteine and dithiothreitol, was found to promote the conversion to GSe - significantly. In addition, disproportionation of GSeSR to 1 and RSSR, which would be initiated by heterolytic cleavage of the Se-S bond and catalyzed by the generated selenolate, was observed. On the basis of these redox behaviors, it was proposed that the heterolytic cleavage of the Se-S bond can be facilitated by the interaction between the Se atom and an amino or aromatic group, which is present at the GPx active site. On the other hand, when a catalytic amount of 1 was reacted with scrambled 4S species of RNase A in the presence of NADPH and glutathione reductase, native protein was efficiently regenerated, suggesting a potential use of 1 to repair misfolded proteins through reduction of the non-native SS bonds.

Apoptosis inducing factor (AIF) mediates lethal redox stress induced by menadione.

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Wiraswati, Hesti Lina; Hangen, Emilie; Sanz, Ana Belén; Lam, Ngoc-Vy; Reinhardt, Camille; Sauvat, Allan; Mogha, Ariane; Ortiz, Alberto; Kroemer, Guido; Modjtahedi, Nazanine

2016-11-22

Mitochondrial apoptosis inducing factor (AIF) is a redox-active enzyme that participates to the biogenesis/maintenance of complex I of the respiratory chain, yet also contributes to catabolic reactions in the context of regulated cell death when AIF translocates to the cytosol and to the nucleus. Here we explore the contribution of AIF to cell death induced by menadione (2-methyl-1,4-naphtoquinone; also called vitamin K3) in conditions in which this pro-oxidant does not cause the mitochondrial release of AIF, yet causes caspase-independent cell killing. Depletion of AIF from human cancer cells reduced the cytotoxicity of menadione. This cytoprotective effect was accompanied by the maintenance of high levels of reduced glutathione (GSH), which are normally depleted by menadione. In addition, AIF depletion reduced the arylation of cellular proteins induced by menadione. This menadione-triggered arylation, which can be measured by a fluorescence assay, is completely suppressed by addition of exogenous glutathione or N-acetyl cysteine. Complex I inhibition by Rotenone did not mimic the cytoprotective action of AIF depletion. Altogether, these results are compatible with the hypothesis that mitochondrion-sessile AIF facilitates lethal redox cycling of menadione, thereby precipitating protein arylation and glutathione depletion.

Compartmentation of redox metabolism in malaria parasites.

Directory of Open Access Journals (Sweden)

Sebastian Kehr

Full Text Available Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito - a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes--glutathione reductase and thioredoxin reductase--Plasmodium makes use of alternative-translation-initiation (ATI to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention.

Redox characteristics of the eukaryotic cytosol

DEFF Research Database (Denmark)

López-Mirabal, H Reynaldo; Winther, Jakob R

2007-01-01

The eukaryotic cytoplasm has long been regarded as a cellular compartment in which the reduced state of protein cysteines is largely favored. Under normal conditions, the cytosolic low-molecular weight redox buffer, comprising primarily of glutathione, is highly reducing and reactive oxygen species...... (ROS) and glutathionylated proteins are maintained at very low levels. In the present review, recent progress in the understanding of the cytosolic thiol-disulfide redox metabolism and novel analytical approaches to studying cytosolic redox properties are discussed. We will focus on the yeast model...... organism, Saccharomyces cerevisiae, where the combination of genetic and biochemical approaches has brought us furthest in understanding the mechanisms underlying cellular redox regulation. It has been shown in yeast that, in addition to the enzyme glutathione reductase, other mechanisms may exist...

The Analgesic Acetaminophen and the Antipsychotic Clozapine Can Each Redox-Cycle with Melanin.

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Temoçin, Zülfikar; Kim, Eunkyoung; Li, Jinyang; Panzella, Lucia; Alfieri, Maria Laura; Napolitano, Alessandra; Kelly, Deanna L; Bentley, William E; Payne, Gregory F

2017-12-20

Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context. The brain has a complex redox context with steep local gradients in O 2 that can promote redox-cycling between melanin and diffusible redox-active chemical species. Here, we performed in vitro reverse engineering studies and report that melanins can redox-cycle with two common redox-active drugs. Experimentally, we used two melanin models: a convenient natural melanin derived from cuttlefish (Sepia melanin) and a synthetic cysteinyldopamine-dopamine core-shell model of neuromelanin. One drug, acetaminophen (APAP), has been used clinically for over a century, and recent studies suggest that low doses of APAP can protect the brain from oxidative-stress-induced toxicity and neurodegeneration, while higher doses can have toxic effects in the brain. The second drug, clozapine (CLZ), is a second generation antipsychotic with polypharmacological activities that remain incompletely understood. These in vitro observations suggest that the redox activities of drugs may be relevant to their modes-of-action, and that melanins may interact with drugs in ways that affect their activities, metabolism, and toxicities.

Unusual thiol-based redox metabolism of parasitic flukes.

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Tripathi, Timir; Suttiprapa, Sutas; Sripa, Banchob

2017-08-01

Parasitic flukes are exposed to free radicals and, to a greater extent, reactive oxygen species (ROS) during their life cycle. Despite being relentlessly exposed to ROS released by activated immune cells, these parasites can survive for many years in the host. Cellular thiol-based redox metabolism plays a crucial role in parasite survival within their hosts. Evidence shows that oxidative stress and redox homeostasis maintenance are important clinical and pathobiochemical as well as effective therapeutic principles in various diseases. The characterization of redox and antioxidant enzymes is likely to yield good target candidates for novel drugs and vaccines. The absence of active catalase in fluke parasites offers great potential for the development of chemotherapeutic agents that act by perturbing the redox equilibrium of the cell. One of the redox-sensitive enzymes, thioredoxin glutathione reductase (TGR), has been accepted as a drug target against blood fluke infections, and related clinical trials are in progress. TGR is the sole enzyme responsible for Trx and GSH reduction in parasitic flukes. The availability of helminth genomes has accelerated the research on redox metabolism of flukes; however, significant achievements have yet to be attained. The present review summarizes current knowledge on the redox and antioxidant system of the parasitic flukes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An assessment of the role of redox cycling in mediating the toxicity of paraquat and nitrofurantoin

Energy Technology Data Exchange (ETDEWEB)

Adam, A.; Cohen, G.M. (Univ. of London (England)); Smith, L.L. (Imperial Chemical Industries plc, Cheshire (England))

1990-04-01

The abilities of paraquat, diquat, and nitrofurantoin to undergo cyclic oxidation and reduction with rat microsomal systems have been assessed and compared to that of the potent redox cycler, menadione. Diquat and menadione were found to be potent redox cyclers with comparable abilities to elicit a nonstoichiometric increase in both the consumption of O{sub 2} and the oxidation of NADPH, compared to the amounts of substrate added. In contrast, paraquat and nitrofurantoin redox cycled poorly, being an order of magnitude less potent than either diquat or menadione. This was reflected in kinetic studies using lung and liver microsomes. In order to assess redox cycling of the substrates in an intact lung system, the O{sub 2} consumption of rat lung slices was measured in the presence of all four compounds. A small increase in lung slice O{sub 2} uptake was observed with paraquat in the first 2.5 hr of incubation, possibly because of redox cycling of a high intracellular concentration of paraquat resulting from active accumulation into target cells. This stimulation in O{sub 2} uptake was no longer observed when slices were incubated for a longer period or with higher paraquat concentrations (10{sup {minus}4}M), possibly because of toxic effects in target cells. These results together with the poor ability to redox cycle with microsomes and the absence of a specific uptake system highlight the problem of associating redox cycling and oxidative stress in the mechanism of nitrofurantoin toxicity.

Corneal endothelial glutathione after photodynamic change

International Nuclear Information System (INIS)

Hull, D.S.; Riley, M.V.; Csukas, S.; Green, K.

1982-01-01

Rabbit corneal endothelial cells perfused with 5 X 10(-6)M rose bengal and exposed to incandescent light demonstrated no alteration of either total of or percent oxidized glutathione after 1 hr. Addition of 5400 U/ml catalase to the perfusing solution had no effect on total glutathione levels but caused a marked reduction in percent oxidized glutathione in corneas exposed to light as well as in those not exposed to light. Substitution of sucrose for glucose in the perfusing solution had no effect on total or percent oxidized glutathione. Perfusion of rabbit corneal endothelium with 0.5 mM chlorpromazine and exposure to ultraviolet (UV) light resulted in no change in total glutathione content. A marked reduction in percent oxidized glutathione occurred, however, in corneas perfused with 0.5 mM chlorpromazine both in the presence and absence of UV light. It is concluded that photodynamically induced swelling of corneas is not the result of a failure of the glutathione redox system

Microfluidic sensor for ultra high redox cycling amplification for highly selective electrochemical measurements

NARCIS (Netherlands)

Odijk, Mathieu; Straver, Martin; Olthuis, Wouter; van den Berg, Albert

2011-01-01

In this contribution a SU8/glass-based microfluidic sensor is described with two closely spaced parallel electrodes for highly selective measurements using the redox cycling (RC) effect. Using this sensor, a RC amplification of ~2000x is measured using the ferrocyanide redox couple, which is much

Compartment specific importance of glutathione during abiotic and biotic stress

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Bernd eZechmann

2014-10-01

Full Text Available The tripeptide thiol glutathione (γ-L-glutamyl-L-cysteinyl-glycine is the most important sulfur containing antioxidant in plants and essential for plant defense against abiotic and biotic stress conditions. It is involved in the detoxification of reactive oxygen species, redox signaling, the modulation of defense gene expression and important for the regulation of enzymatic activities. Even though changes in glutathione contents are well documented in plants and its roles in plant defense are well established, still too little is known about its compartment specific importance during abiotic and biotic stress conditions. Due to technical advances in the visualization of glutathione and the redox state of plants through microscopical methods some progress was made in the last few years in studying the importance of subcellular glutathione contents during stress conditions in plants. This review summarizes the data available on compartment specific importance of glutathione in the protection against abiotic and biotic stress conditions such as high light stress, exposure to cadmium, drought, and pathogen attack (Pseudomonas, Botrytis, Tobacco Mosaic Virus. The data will be discussed in connection with the subcellular accumulation of ROS during these conditions and glutathione synthesis which are both highly compartment specific (e.g. glutathione synthesis takes place in chloroplasts and the cytosol. Thus this review will reveal the compartment specific importance of glutathione during abiotic and biotic stress conditions.

Determination of glutathione and glutathione disulfide in biological samples: an in-depth review.

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Monostori, Péter; Wittmann, Gyula; Karg, Eszter; Túri, Sándor

2009-10-15

Glutathione (GSH) is a thiol-containing tripeptide, which plays central roles in the defence against oxidative damage and in signaling pathways. Upon oxidation, GSH is transformed to glutathione disulfide (GSSG). The concentrations of GSH and GSSG and their molar ratio are indicators of cell functionality and oxidative stress. Assessment of redox homeostasis in various clinical states and medical applications for restoration of the glutathione status are of growing importance. This review is intended to provide a state-of-the-art overview of issues relating to sample pretreatment and choices for the separation and detection of GSH and GSSG. High-performance liquid chromatography, capillary electrophoresis and gas chromatography (as techniques with a separation step) with photometric, fluorimetric, electrochemical and mass spectrometric detection are discussed, stress being laid on novel approaches.

Zinc and the modulation of redox homeostasis

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Oteiza, Patricia I.

2012-01-01

Zinc, a redox inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintain the cell redox balance through different mechanisms including: i) the regulation of oxidant production and metal-induced oxidative damage; ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione and other thiol oxidant species; iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and act per se scavenging oxidants; iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue disfunction in cell and animal models of zinc deficiency, stress the relevant role of zinc in the preservation of cell redox homeostasis. However, while the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the involved molecules, targets and mechanisms are still partially known and the subject of active research. PMID:22960578

Chloroplastic thioredoxin-f and thioredoxin-m1/4 play important roles in brassinosteroids-induced changes in CO2 assimilation and cellular redox homeostasis in tomato

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Cheng, Fei; Zhou, Yan-Hong; Xia, Xiao-Jian; Shi, Kai; Zhou, Jie; Yu, Jing-Quan

2014-01-01

Chloroplast thioredoxins (TRXs) and glutathione function as redox messengers in the regulation of photosynthesis. In this work, the roles of chloroplast TRXs in brassinosteroids (BRs)-induced changes in cellular redox homeostasis and CO2 assimilation were studied in the leaves of tomato plants. BRs-deficient d ^im plants showed decreased transcripts of TRX-f, TRX-m2, TRX-m1/4, and TRX-x, while exogenous BRs significantly induced CO2 assimilation and the expression of TRX-f, TRX-m2, TRX-m1/4, and TRX-x. Virus-induced gene silencing (VIGS) of the chloroplast TRX-f, TRX-m2, TRX-m1/4, and TRX-y genes individually increased membrane lipid peroxidation and accumulation of 2-Cys peroxiredoxin dimers, and decreased the activities of the ascorbate–glutathione cycle enzymes and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in the leaves. Furthermore, partial silencing of TRX-f, TRX-m2, TRX-m1/4, and TRX-y resulted in decreased expression of genes involved in the Benson–Calvin cycle and decreased activity of the associated enzymes. Importantly, the BRs-induced increase in CO2 assimilation and the increased expression and activities of antioxidant- and photosynthesis-related genes and enzymes were compromised in the partially TRX-f- and TRX-m1/4-silenced plants. All of these results suggest that TRX-f and TRX-m1/4 are involved in the BRs-induced changes in CO2 assimilation and cellular redox homeostasis in tomato. PMID:24847092

RED BLOOD CELL AND WHOLE BLOOD GLUTATHIONE REDOX STATUS IN ENDURANCE-TRAINED MEN FOLLOWING A SKI MARATHON

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Eve Unt

2008-09-01

Full Text Available The aim of the present study was to evaluate the changes in glutathione redox ratio (GSSG·GSH-1 in red blood cells (RBCs and whole blood in well-trained men following a ski marathon. 16 male subjects (27.0 ± 4.7 yrs, 1.81 ± 0.06 m, 77.6 ± 9.6 kg, VO2max 66.2 ± 5.7 ml·kg-1·min-1 were examined before the competition (pre- COMP, after the competition (post-COMP and during an 18-hour recovery period (RECOV. There was a slight decrease in reduced glutathione (GSH in blood and in RBCs in post-COMP. During RECOV, the GSH level in blood was reduced, the GSH level in RBCs was significantly elevated (a statistically significant difference as compared to the pre-COMP level. The post-COMP GSSG·GSH-1 in full blood did not increase significantly, but its increase was statistically significant during the 18-hour recovery period. During the post-COMP and RECOV, the GSSG·GSH-1 in RBCs slightly decreased in comparison with the pre-COMP. Vitamin C concentration in serum increased in post-COMP (49% vs. pre- COMP and decreased to the baseline level during RECOV. In conclusion, our data show that acute exercise slightly increases the GSSG·GSH-1 in whole blood, while GSSG·GSH-1 in RBCs significantly decreases. Thus, exercise-related changes in the non-enzymatic components of the glutathione system (GSSG and GSH in whole blood and RBCs are not identical

Revisiting the BaO2/BaO redox cycle for solar thermochemical energy storage.

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Carrillo, A J; Sastre, D; Serrano, D P; Pizarro, P; Coronado, J M

2016-03-21

The barium peroxide-based redox cycle was proposed in the late 1970s as a thermochemical energy storage system. Since then, very little attention has been paid to such redox couples. In this paper, we have revisited the use of reduction-oxidation reactions of the BaO2/BaO system for thermochemical heat storage at high temperatures. Using thermogravimetric analysis, reduction and oxidation reactions were studied in order to find the main limitations associated with each process. Furthermore, the system was evaluated through several charge-discharge stages in order to analyse its possible degradation after repeated cycling. Through differential scanning calorimetry the heat stored and released were also determined. Oxidation reaction, which was found to be slower than reduction, was studied in more detail using isothermal tests. It was observed that the rate-controlling step of BaO oxidation follows zero-order kinetics, although at high temperatures a deviation from Arrhenius behaviour was observed probably due to hindrances to anionic oxygen diffusion caused by the formation of an external layer of BaO2. This redox couple was able to withstand several redox cycles without deactivation, showing reaction conversions close to 100% provided that impurities are previously eliminated through thermal pre-treatment, demonstrating the feasibility of this system for solar thermochemical heat storage.

Inhibition of glutathione biosynthesis alters compartmental redox status and the thiol proteome in organogenesis-stage rat conceptuses.

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Harris, Craig; Shuster, Daniel Z; Roman Gomez, Rosaicela; Sant, Karilyn E; Reed, Matthew S; Pohl, Jan; Hansen, Jason M

2013-10-01

Developmental signals that control growth and differentiation are regulated by environmental factors that generate reactive oxygen species (ROS) and alter steady-state redox environments in tissues and fluids. Protein thiols are selectively oxidized and reduced in distinct spatial and temporal patterns in conjunction with changes in glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) redox potentials (E(h)) to regulate developmental signaling. The purpose of this study was to measure compartment-specific thiol redox status in cultured organogenesis-stage rat conceptuses and to evaluate the impact of thiol oxidation on the redox proteome. The visceral yolk sac (VYS) has the highest initial (0 h) total intracellular GSH (GSH+2GSSG) concentration (5.5 mM) and the lowest Eh (-223 mV) as determined by HPLC analysis. Total embryo (EMB) GSH concentrations ranged lower (3.2 mM) and were only slightly more oxidized than the VYS. Total GSH concentrations in yolk sac fluid (YSF) and amniotic fluid (AF) are >500-fold lower than in tissues and are highly oxidized (YSF E(h)=-121 mV and AF E(h)=-49 mV). Steady-state total Cys concentrations (Cys+2CySS) were significantly lower than GSH in tissues but were otherwise equal in VYS and EMB near 0.5 mM. On gestational day 11, total GSH and Cys concentrations in EMB and VYS increase significantly over the 6h time course while E(h) remains relatively constant. The Eh (GSH/GSSG) in YSF and AF become more reduced over time while E(h) (Cys/CySS) become more oxidized. Addition of L-buthionine-S,R-sulfoximine (BS0) to selectively inhibit GSH synthesis and mimic the effects of some GSH-depleting environmental chemicals significantly decreased VYS and EMB GSH and Cys concentrations and increased Eh over the 6h exposure period, showing a greater overall oxidation. In the YSF, BSO caused a significant increase in total Cys concentrations to 1.7 mM but did not significantly change the E(h) for Cys/CySS. A significant net

Interaction between heavy metals and thiol-linked redox reactions in germination.

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Smiri, M; Chaoui, A; Ferjani, E E

2010-09-15

Thioredoxin (TRX) proteins perform important biological functions in cells by changing the redox state of proteins via dithiol disulfide exchange. Several systems are able to control the activity, stability, and correct folding of enzymes through dithiol/disulfide isomerization reactions including the enzyme protein disulfide-isomerase, the glutathione-dependent glutaredoxin system, and the thioredoxin systems. Plants have devised sophisticated mechanisms to cope with biotic and abiotic stresses imposed by their environment. Among these mechanisms, those collectively referred to as redox reactions induced by endogenous systems. This is of agronomical importance since a better knowledge of the involved mechanisms can offer novel means for crop protection. In the plant life cycle, the seed and seedling stages are key developmental stages conditioning the final yield of crops. Both are very sensitive to heavy metal stress. Plant redox reactions are principally studied on adult plant organs and there is only very scarce informations about the onset of redox regulation at the level of seed germination. In the here presented study, we discussed the importance of redox proteins in plant cell metabolism and defence. Special focus is given to TRX, which are involved in detoxification of ROS and also to their targets.

Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide

DEFF Research Database (Denmark)

López-Mirabal, H Reynaldo; Thorsen, Michael; Kielland-Brandt, Morten C

2007-01-01

Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma-glutamyl-c......Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma...... antioxidant pools of glutathione (GSH) and thioredoxin are required for resistance to DPS. We found that DPS-sensitive mutants display increases in the disulfide form of GSH (GSSG) during DPS exposure that roughly correlate with their more oxidizing GSH redox potential in the cytosol and their degree of DPS...

The effect of bicarbonate on menadione-induced redox cycling and cytotoxicity: potential involvement of the carbonate radical.

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Aljuhani, Naif; Michail, Karim; Karapetyan, Zubeida; Siraki, Arno G

2013-10-01

We have investigated the effect of NaHCO3 on menadione redox cycling and cytotoxicity. A cell-free system utilized menadione and ascorbic acid to catalyze a redox cycle, and we utilized murine hepatoma (Hepa 1c1c7) cells for in vitro experiments. Experiments were performed using low (2 mmol/L) and physiological (25 mmol/L) levels of NaHCO3 in buffer equilibrated to physiological pH. Using oximetry, ascorbic acid oxidation, and ascorbyl radical detection, we found that menadione redox cycling was enhanced by NaHCO3. Furthermore, Hepa 1c1c7 cells treated with menadione demonstrated cytotoxicity that was significantly increased with physiological concentrations of NaHCO3 in the media, compared with low levels of NaHCO3. Interestingly, the inhibition of superoxide dismutase (SOD) with 2 different metal chelators was associated with a protective effect against menadione cytotoxicity. Using isolated protein, we found a significant increase in protein carbonyls with menadione-ascorbate-SOD with physiological NaHCO3 levels; low NaHCO3 or SOD-free reactions produced lower levels of protein carbonyls. In conclusion, these findings suggest that the hydrogen peroxide generated by menadione redox cycling together with NaHCO3-CO2 are potential substrates for SOD peroxidase activity that can lead to carbonate-radical-enhanced cytotoxicity. These findings demonstrate the importance of NaHCO3 in menadione redox cycling and cytotoxicity.

Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement.

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Wu, Junjun; Zhang, Xia; Zhou, Peng; Huang, Jiaying; Xia, Xiudong; Li, Wei; Zhou, Ziyu; Chen, Yue; Liu, Yinghao; Dong, Mingsheng

2017-11-01

Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C 6 -C 10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield. Furthermore, the introduction of formate dehydrogenase from Candida boidinii using fermentative inhibitor byproduct formate as a redox NADH sink improved MCFA titer from initial 1.2g/L to 3.1g/L. Moreover, coupling of increasing the supply of acetyl-CoA with NADH to achieve fermentative redox balance enabled product synthesis at maximum titers. To this end, the acetate re-assimilation pathway was further optimized to increase acetyl-CoA availability associated with the new supply of NADH. It was found that the acetyl-CoA synthetase activity and intracellular ATP levels constrained the activity of acetate re-assimilation pathway, and 4.7g/L of MCFA titer was finally achieved after alleviating these two limiting factors. To the best of our knowledge, this represented the highest titer reported to date. These results demonstrated that the key constraint of r-BOX was redox imbalance and redox engineering could further unleash the lipogenic potential of this cycle. The redox engineering strategies could be applied to acetyl-CoA-derived products or other bio-products requiring multiple redox cofactors for biosynthesis. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Preservation of organic matter in nontronite against iron redox cycling.

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Zeng, Q.

2015-12-01

It is generally believed that clay minerals can protect organic matter from degradation in redox active environments, but both biotic and abiotic factors can influence the redox process and thus potentially change the clay-organic associations. However, the specific mechanisms involved in this process remain poorly understood. In this study, a model organic compound, 12-Aminolauric acid (ALA) was selected to intercalate into the structural interlayer of nontronite (an iron-rich smectite, NAu-2) to form an ALA-intercalated NAu-2 composite (ALA-NAu-2). Shawanella putrefaciens CN32 and sodium dithionite were used to reduce structural Fe(III) to Fe(II) in NAu-2 and ALA-NAu-2. The bioreduced ALA-NAu-2 was subsequently re-oxidized by air. The rates and extents of bioreduction and air re-oxidation were determined with wet chemistry methods. ALA release from ALA-NAu-2 via redox process was monitored. Mineralogical changes after iron redox cycle were investigated with X-ray diffraction, infrared spectroscopy, and scanning and transmission electron microscopy. At the beginning stage of bioreduction, S. putrefaciens CN32 reduced Fe(III) from the edges of nontronite and preferentially reduced and dissolved small and poorly crystalline particles, and released ALA, resulting a positive correlation between ALA release and iron reduction extent (80%). Because bacteria are the principal agent for mediating redox process in natural environments, our results demonstrated that the structural interlayer of smectite can serve as a potential shelter to protect organic matter from oxidation.

Amplified and in situ detection of redox-active metabolite using a biobased redox capacitor.

Science.gov (United States)

Kim, Eunkyoung; Gordonov, Tanya; Bentley, William E; Payne, Gregory F

2013-02-19

Redox cycling provides a mechanism to amplify electrochemical signals for analyte detection. Previous studies have shown that diverse mediators/shuttles can engage in redox-cycling reactions with a biobased redox capacitor that is fabricated by grafting redox-active catechols onto a chitosan film. Here, we report that redox cycling with this catechol-chitosan redox capacitor can amplify electrochemical signals for detecting a redox-active bacterial metabolite. Specifically, we studied the redox-active bacterial metabolite pyocyanin that is reported to be a virulence factor and signaling molecule for the opportunistic pathogen P. aeruginosa. We demonstrate that redox cycling can amplify outputs from various electrochemical methods (cyclic voltammetry, chronocoulometry, and differential pulse voltammetry) and can lower the detection limit of pyocyanin to 50 nM. Further, the compatibility of this biobased redox capacitor allows the in situ monitoring of the production of redox-active metabolites (e.g., pyocyanin) during the course of P. aeruginosa cultivation. We anticipate that the amplified output of redox-active virulence factors should permit an earlier detection of life-threatening infections by the opportunistic pathogen P. aeruginosa while the "bio-compatibility" of this measurement approach should facilitate in situ study of the spatiotemporal dynamics of bacterial redox signaling.

Solar fuel processing efficiency for ceria redox cycling using alternative oxygen partial pressure reduction methods

International Nuclear Information System (INIS)

Lin, Meng; Haussener, Sophia

2015-01-01

Solar-driven non-stoichiometric thermochemical redox cycling of ceria for the conversion of solar energy into fuels shows promise in achieving high solar-to-fuel efficiency. This efficiency is significantly affected by the operating conditions, e.g. redox temperatures, reduction and oxidation pressures, solar irradiation concentration, or heat recovery effectiveness. We present a thermodynamic analysis of five redox cycle designs to investigate the effects of working conditions on the fuel production. We focused on the influence of approaches to reduce the partial pressure of oxygen in the reduction step, namely by mechanical approaches (sweep gassing or vacuum pumping), chemical approaches (chemical scavenger), and combinations thereof. The results indicated that the sweep gas schemes work more efficient at non-isothermal than isothermal conditions, and efficient gas phase heat recovery and sweep gas recycling was important to ensure efficient fuel processing. The vacuum pump scheme achieved best efficiencies at isothermal conditions, and at non-isothermal conditions heat recovery was less essential. The use of oxygen scavengers combined with sweep gas and vacuum pump schemes further increased the system efficiency. The present work can be used to predict the performance of solar-driven non-stoichiometric redox cycles and further offers quantifiable guidelines for system design and operation. - Highlights: • A thermodynamic analysis was conducted for ceria-based thermochemical cycles. • Five novel cycle designs and various operating conditions were proposed and investigated. • Pressure reduction method affects optimal operating conditions for maximized efficiency. • Chemical oxygen scavenger proves to be promising in further increasing efficiency. • Formulation of quantifiable design guidelines for economical competitive solar fuel processing

Ceria-based electrospun fibers for renewable fuel production via two-step thermal redox cycles for carbon dioxide splitting.

Science.gov (United States)

Gibbons, William T; Venstrom, Luke J; De Smith, Robert M; Davidson, Jane H; Jackson, Gregory S

2014-07-21

Zirconium-doped ceria (Ce(1-x)Zr(x)O2) was synthesized through a controlled electrospinning process as a promising approach to cost-effective, sinter-resistant material structures for high-temperature, solar-driven thermochemical redox cycles. To approximate a two-step redox cycle for solar fuel production, fibrous Ce(1-x)Zr(x)O2 with relatively low levels of Zr-doping (0 rates of O2 release during reduction and CO production during reoxidation and by assessing post-cycling fiber crystallite sizes and surface areas. Sintering increases with reduction temperature but occurs primarily along the fiber axes. Even after 108 redox cycles with reduction at 1400 °C and oxidation with CO2 at 800 °C, the fibers maintain their structure with surface areas of ∼0.3 m(2) g(-1), higher than those observed in the literature for other ceria-based structures operating at similarly high temperature conditions. Total CO production and peak production rate stabilize above 3.0 mL g(-1) and 13.0 mL min(-1) g(-1), respectively. The results show the potential for electrospun oxides as sinter-resistant material structures with adequate surface area to support rapid CO2 splitting in solar thermochemical redox cycles.

Electrochemical study of quinone redox cycling: A novel application of DNA-based biosensors for monitoring biochemical reactions.

Science.gov (United States)

Ensafi, Ali A; Jamei, Hamid Reza; Heydari-Bafrooei, Esmaeil; Rezaei, B

2016-10-01

This paper presents the results of an experimental investigation of voltammetric and impedimetric DNA-based biosensors for monitoring biological and chemical redox cycling reactions involving free radical intermediates. The concept is based on associating the amounts of radicals generated with the electrochemical signals produced, using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). For this purpose, a pencil graphite electrode (PGE) modified with multiwall carbon nanotubes and poly-diallydimethlammonium chloride decorated with double stranded fish sperm DNA was prepared to detect DNA damage induced by the radicals generated from a redox cycling quinone (i.e., menadione (MD; 2-methyl-1,4-naphthoquinone)). Menadione was employed as a model compound to study the redox cycling of quinones. A direct relationship was found between free radical production and DNA damage. The relationship between MD-induced DNA damage and free radical generation was investigated in an attempt to identify the possible mechanism(s) involved in the action of MD. Results showed that DPV and EIS were appropriate, simple and inexpensive techniques for the quantitative and qualitative comparisons of different reducing reagents. These techniques may be recommended for monitoring DNA damages and investigating the mechanisms involved in the production of redox cycling compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparing the performances of electrochemical sensors using p-aminophenol redox cycling by different reductants on gold electrodes modified with self-assembled monolayers

International Nuclear Information System (INIS)

Xia, Ning; Ma, Fengji; Zhao, Feng; He, Qige; Du, Jimin; Li, Sujuan; Chen, Jing; Liu, Lin

2013-01-01

Highlights: • Performances of p-AP redox cycling using different reductants on gold surface are compared. • Background current decreases in order of hydrazine, Na 2 SO 3 , NaBH 4 , NADH, cysteamine, and TCEP. • Chemical reaction rate with QI increases in order of NADH, TCEP, and cysteamine. • NADH, TCEP and cysteamine are suitable for p-AP redox cycling on gold electrode. -- Abstract: p-Aminophenol (p-AP) redox cycling using chemical reductants is one strategy for developing sensitive electrochemical sensors. However, most of the reported reductants are only used on indium-tin oxide (ITO) electrodes but not gold electrodes due to the high background current caused by the oxidation reaction of the reductants on the highly electrocatalytic gold electrodes. Therefore, new strategies and/or reductants are in demand for expanding the application of p-AP redox cycling on gold electrodes. In this work, we compared the performances of several reductants in p-AP redox cycling on self-assembled monolayers (SAMs)-modified gold electrodes. Among the tested reagents, nicotinamide adenine dinucleotide (NADH), tris(2-carboxyethyl)phosphine (TCEP) and cysteamine were demonstrated to be suitable for p-AP redox cycling on the alkanethiol-modified gold electrodes because of their low background current. The rate of chemical reaction between reductants and p-quinone imine (QI, the electrochemically oxidized product of p-AP) increases in the order of NADH −1 was achieved. We believe that our work will be valuable for the development of electrochemical sensors using p-AP redox cycling on gold electrodes

Disruption of Pyridine Nucleotide Redox Status During Oxidative Challenge at Normal and Low-Glucose States: Implications for Cellular Adenosine Triphosphate, Mitochondrial Respiratory Activity, and Reducing Capacity in Colon Epithelial Cells

Science.gov (United States)

Circu, Magdalena L.; Maloney, Ronald E.

2011-01-01

Abstract We recently demonstrated that menadione (MQ), a redox cycling quinone, mediated the loss of mitochondrial glutathione/glutathione disulfide redox balance. In this study, we showed that MQ significantly disrupted cellular pyridine nucleotide (NAD+/NADH, NADP+/NADPH) redox balance that compromised cellular ATP, mitochondrial respiratory activity, and NADPH-dependent reducing capacity in colonic epithelial cells, a scenario that was exaggerated by low glucose. In the cytosol, MQ induced NAD+ loss concurrent with increased NADP+ and NAD kinase activity, but decreased NADPH. In the mitochondria, NADH loss occurred in conjunction with increased nicotinamide nucleotide transhydrogenase activity and NADP+, and decreased NADPH. These results are consistent with cytosolic NAD+-to-NADP+ and mitochondrial NADH-to-NADPH shifts, but compromised NADPH availability. Thus, despite the sacrifice of NAD+/NADH in favor of NADPH generation, steady-state NADPH levels were not maintained during MQ challenge. Impairments of cellular bioenergetics were evidenced by ATP losses and increased mitochondrial O2 dependence of pyridine nucleotide oxidation–reduction; half-maximal oxidation (P50) was 10-fold higher in low glucose, which was lowered by glutamate or succinate supplementation. This exaggerated O2 dependence is consistent with increased O2 diversion to nonmitochondrial O2 consumption by MQ-semiquinone redox cycling secondary to decreased NADPH-dependent MQ detoxication at low glucose, a situation that was corrected by glucose-sparing mitochondrial substrates. Antioxid. Redox Signal. 14, 2151–2162. PMID:21083422

Oxidative protein folding: from thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum.

Science.gov (United States)

Hudson, Devin A; Gannon, Shawn A; Thorpe, Colin

2015-03-01

This review examines oxidative protein folding within the mammalian endoplasmic reticulum (ER) from an enzymological perspective. In protein disulfide isomerase-first (PDI-first) pathways of oxidative protein folding, PDI is the immediate oxidant of reduced client proteins and then addresses disulfide mispairings in a second isomerization phase. In PDI-second pathways the initial oxidation is PDI-independent. Evidence for the rapid reduction of PDI by reduced glutathione is presented in the context of PDI-first pathways. Strategies and challenges are discussed for determination of the concentrations of reduced and oxidized glutathione and of the ratios of PDI(red):PDI(ox). The preponderance of evidence suggests that the mammalian ER is more reducing than first envisaged. The average redox state of major PDI-family members is largely to almost totally reduced. These observations are consistent with model studies showing that oxidative protein folding proceeds most efficiently at a reducing redox poise consistent with a stoichiometric insertion of disulfides into client proteins. After a discussion of the use of natively encoded fluorescent probes to report the glutathione redox poise of the ER, this review concludes with an elaboration of a complementary strategy to discontinuously survey the redox state of as many redox-active disulfides as can be identified by ratiometric LC-MS-MS methods. Consortia of oxidoreductases that are in redox equilibrium can then be identified and compared to the glutathione redox poise of the ER to gain a more detailed understanding of the factors that influence oxidative protein folding within the secretory compartment. Copyright © 2014 Elsevier Inc. All rights reserved.

Computational Modeling of the Catalytic Cycle of Glutathione Peroxidase Nanomimic.

Science.gov (United States)

Kheirabadi, Ramesh; Izadyar, Mohammad

2016-12-29

To elucidate the role of a derivative of ebselen as a mimic of the antioxidant selenoenzyme glutathione peroxidase, density functional theory and solvent-assisted proton exchange (SAPE) were applied to model the reaction mechanism in a catalytic cycle. This mimic plays the role of glutathione peroxidase through a four-step catalytic cycle. The first step is described as the oxidation of 1 in the presence of hydrogen peroxide, while selenoxide is reduced by methanthiol at the second step. In the third step of the reaction, the reduction of selenenylsulfide occurs by methanthiol, and the selenenic acid is dehydrated at the final step. Based on the kinetic parameters, step 4 is the rate-determining step (RDS) of the reaction. The bond strength of the atoms involved in the RDS is discussed with the quantum theory of atoms in molecules (QTAIM). Low value of electron density, ρ(r), and positive Laplacian values are the evidence for the covalent nature of the hydrogen bonds rupture (O 30 -H 31 , O 33 -H 34 ). A change in the sign of the Laplacian, L(r), from the positive value in the reactant to a negative character at the transition state indicates the depletion of the charge density, confirming the N 5 -H 10 and O 11 -Se 1 bond breaking. The analysis of electron location function (ELF) and localized orbital locator (LOL) of the Se 1 -N 5 and Se 1 -O 11 bonds have been done by multi-WFN program. High values of ELF and LOL at the transition state regions between the Se, N, and O atoms display the bond formation. Finally, the main donor-acceptor interaction energies were analyzed using the natural bond orbital analysis for investigation of their stabilization effects on the critical bonds at the RDS.

Mechanistic insight provided by glutaredoxin within a fusion to redox-sensitive yellow fluorescent protein

DEFF Research Database (Denmark)

Björnberg, Olof; Østergaard, Henrik; Winther, Jakob R

2006-01-01

Redox-sensitive yellow fluorescent protein (rxYFP) contains a dithiol disulfide pair that is thermodynamically suitable for monitoring intracellular glutathione redox potential. Glutaredoxin 1 (Grx1p) from yeast is known to catalyze the redox equilibrium between rxYFP and glutathione, and here, we...... have generated a fusion of the two proteins, rxYFP-Grx1p. In comparison to isolated subunits, intramolecular transfer of reducing equivalents made the fusion protein kinetically superior in reactions with glutathione. The rate of GSSG oxidation was thus improved by a factor of 3300. The reaction...... separately and in the fusion. This could not be ascribed to the lack of an unproductive side reaction to glutaredoxin disulfide. Instead, slower alkylation kinetics with iodoacetamide indicates a better leaving-group capability of the remaining cysteine residue, which can explain the increased activity....

Redox regulation of Rac1 by thiol oxidation

Science.gov (United States)

Hobbs, G. Aaron; Mitchell, Lauren E.; Arrington, Megan E.; Gunawardena, Harsha P.; DeCristo, Molly J.; Loeser, Richard F.; Chen, Xian; Cox, Adrienne D.; Campbell, Sharon L.

2016-01-01

The Rac1 GTPase is an essential and ubiquitous protein that signals through numerous pathways to control critical cellular processes, including cell growth, morphology, and motility. Rac1 deletion is embryonic lethal, and its dysregulation or mutation can promote cancer, arthritis, cardiovascular disease, and neurological disorders. Rac1 activity is highly regulated by modulatory proteins and posttranslational modifications. Whereas much attention has been devoted to guanine nucleotide exchange factors that act on Rac1 to promote GTP loading and Rac1 activation, cellular oxidants may also regulate Rac1 activation by promoting guanine nucleotide exchange. Herein, we show that Rac1 contains a redox-sensitive cysteine (Cys18) that can be selectively oxidized at physiological pH because of its lowered pKa. Consistent with these observations, we show that Rac1 is glutathiolated in primary chondrocytes. Oxidation of Cys18 by glutathione greatly perturbs Rac1 guanine nucleotide binding and promotes nucleotide exchange. As aspartate substitutions have been previously used to mimic cysteine oxidation, we characterized the biochemical properties of Rac1C18D. We also evaluated Rac1C18S as a redox-insensitive variant and found that it retains structural and biochemical properties similar to those of Rac1WT but is resistant to thiol oxidation. In addition, Rac1C18D, but not Rac1C18S, shows greatly enhanced nucleotide exchange, similar to that observed for Rac1 oxidation by glutathione. We employed Rac1C18D in cell-based studies to assess whether this fast-cycling variant, which mimics Rac1 oxidation by glutathione, affects Rac1 activity and function. Expression of Rac1C18D in Swiss 3T3 cells showed greatly enhanced GTP-bound Rac1 relative to Rac1WT and the redox-insensitive Rac1C18S variant. Moreover, expression of Rac1C18D in HEK-293T cells greatly promoted lamellipodia formation. Our results suggest that Rac1 oxidation at Cys18 is a novel posttranslational modification that

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria

Energy Technology Data Exchange (ETDEWEB)

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

2016-05-16

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia).

Glutathione, Glutaredoxins, and Iron.

Science.gov (United States)

Berndt, Carsten; Lillig, Christopher Horst

2017-11-20

Glutathione (GSH) is the most abundant cellular low-molecular-weight thiol in the majority of organisms in all kingdoms of life. Therefore, functions of GSH and disturbed regulation of its concentration are associated with numerous physiological and pathological situations. Recent Advances: The function of GSH as redox buffer or antioxidant is increasingly being questioned. New functions, especially functions connected to the cellular iron homeostasis, were elucidated. Via the formation of iron complexes, GSH is an important player in all aspects of iron metabolism: sensing and regulation of iron levels, iron trafficking, and biosynthesis of iron cofactors. The variety of GSH coordinated iron complexes and their functions with a special focus on FeS-glutaredoxins are summarized in this review. Interestingly, GSH analogues that function as major low-molecular-weight thiols in organisms lacking GSH resemble the functions in iron homeostasis. Since these iron-related functions are most likely also connected to thiol redox chemistry, it is difficult to distinguish between mechanisms related to either redox or iron metabolisms. The ability of GSH to coordinate iron in different complexes with or without proteins needs further investigation. The discovery of new Fe-GSH complexes and their physiological functions will significantly advance our understanding of cellular iron homeostasis. Antioxid. Redox Signal. 27, 1235-1251.

Study of dimensional changes during redox cycling of oxygen carrier materials for chemical looping combustion

NARCIS (Netherlands)

Fossdal, A.; Darell, O.; Lambert, A.; Schols, E.; Comte, E.; Leenman, R.N.; Blom, R.

2015-01-01

Dimensional and phase changes of four candidate oxygen carrier materials for chemical looping combustion are investigated by dilatometry and high-temperature X-ray diffraction during four redox cycles. NiO/Ni2AlO4 does not exhibit significant dimensional changes during cycling, and it is shown that

A strategy for selective detection based on interferent depleting and redox cycling using the plane-recessed microdisk array electrodes

International Nuclear Information System (INIS)

Zhu Feng; Yan Jiawei; Lu Miao; Zhou Yongliang; Yang Yang; Mao Bingwei

2011-01-01

Highlights: → A novel strategy based on a combination of interferent depleting and redox cycling is proposed for the plane-recessed microdisk array electrodes. → The strategy break up the restriction of selectively detecting a species that exhibits reversible reaction in a mixture with one that exhibits an irreversible reaction. → The electrodes enhance the current signal by redox cycling. → The electrodes can work regardless of the reversibility of interfering species. - Abstract: The fabrication, characterization and application of the plane-recessed microdisk array electrodes for selective detection are demonstrated. The electrodes, fabricated by lithographic microfabrication technology, are composed of a planar film electrode and a 32 x 32 recessed microdisk array electrode. Different from commonly used redox cycling operating mode for array configurations such as interdigitated array electrodes, a novel strategy based on a combination of interferent depleting and redox cycling is proposed for the electrodes with an appropriate configuration. The planar film electrode (the plane electrode) is used to deplete the interferent in the diffusion layer. The recessed microdisk array electrode (the microdisk array), locating within the diffusion layer of the plane electrode, works for detecting the target analyte in the interferent-depleted diffusion layer. In addition, the microdisk array overcomes the disadvantage of low current signal for a single microelectrode. Moreover, the current signal of the target analyte that undergoes reversible electron transfer can be enhanced due to the redox cycling between the plane electrode and the microdisk array. Based on the above working principle, the plane-recessed microdisk array electrodes break up the restriction of selectively detecting a species that exhibits reversible reaction in a mixture with one that exhibits an irreversible reaction, which is a limitation of single redox cycling operating mode. The

In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment.

Science.gov (United States)

Bobko, Andrey A; Eubank, Timothy D; Driesschaert, Benoit; Khramtsov, Valery V

2018-03-16

This protocol demonstrates the capability of low-field electron paramagnetic resonance (EPR)-based techniques in combination with functional paramagnetic probes to provide quantitative information on the chemical tumor microenvironment (TME), including pO2, pH, redox status, concentrations of interstitial inorganic phosphate (Pi), and intracellular glutathione (GSH). In particular, an application of a recently developed soluble multifunctional trityl probe provides unsurpassed opportunity for in vivo concurrent measurements of pH, pO2 and Pi in Extracellular space (HOPE probe). The measurements of three parameters using a single probe allow for their correlation analyses independent of probe distribution and time of the measurements.

Characterization of plasma thiol redox potential in a common marmoset model of aging

Directory of Open Access Journals (Sweden)

James R. Roede

2013-01-01

Full Text Available Due to its short lifespan, ease of use and age-related pathologies that mirror those observed in humans, the common marmoset (Callithrix jacchus is poised to become a standard nonhuman primate model of aging. Blood and extracellular fluid possess two major thiol-dependent redox nodes involving cysteine (Cys, cystine (CySS, glutathione (GSH and glutathione disulfide (GSSG. Alteration in these plasma redox nodes significantly affects cellular physiology, and oxidation of the plasma Cys/CySS redox potential (EhCySS is associated with aging and disease risk in humans. The purpose of this study was to determine age-related changes in plasma redox metabolites and corresponding redox potentials (Eh to further validate the marmoset as a nonhuman primate model of aging. We measured plasma thiol redox states in marmosets and used existing human data with multivariate adaptive regression splines (MARS to model the relationships between age and redox metabolites. A classification accuracy of 70.2% and an AUC of 0.703 were achieved using the MARS model built from the marmoset redox data to classify the human samples as young or old. These results show that common marmosets provide a useful model for thiol redox biology of aging.

Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication

Energy Technology Data Exchange (ETDEWEB)

Jan, Yi-Hua [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Richardson, Jason R., E-mail: jricha3@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Baker, Angela A. [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Mishin, Vladimir [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Health Science, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States)

2015-10-01

Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40 mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. - Highlights: • Menadione redox cycles with cytochrome P450 reductase and generates reactive oxygen species. • Redox cycling inhibits cytochrome P450-mediated parathion metabolism. • Short term administration of menadione inhibits parathion toxicity by inhibiting paraoxon formation.

Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication

International Nuclear Information System (INIS)

Jan, Yi-Hua; Richardson, Jason R.; Baker, Angela A.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

2015-01-01

Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40 mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. - Highlights: • Menadione redox cycles with cytochrome P450 reductase and generates reactive oxygen species. • Redox cycling inhibits cytochrome P450-mediated parathion metabolism. • Short term administration of menadione inhibits parathion toxicity by inhibiting paraoxon formation.

In situ redox cycle of a nickel–YSZ fuel cell anode in an environmental transmission electron microscope

DEFF Research Database (Denmark)

Jeangros, Quentin; Faes, Antonin; Wagner, Jakob Birkedal

2010-01-01

triggers the reduction reaction. During Ni reoxidation, the creation of a porous structure, due to mass transport, accounts for the redox instability of the Ni-based anode. Both the expansion of NiO during a redox cycle and the presence of stress in the yttria-stabilized zirconia grains are observed......Environmental transmission electron microscopy is used in combination with density functional theory calculations to study the redox stability of a nickel/yttria-stabilized zirconia solid oxide fuel cell anode. The results reveal that the transfer of oxygen from NiO to yttria-stabilized zirconia...... directly. Besides providing an understanding of the Ni–YSZ anode redox degradation, the observations are used to propose an alternative anode design for improved redox tolerance....

Antidepressant-like responses in the forced swimming test elicited by glutathione and redox modulation.

Science.gov (United States)

Rosa, Juliana M; Dafre, Alcir Luiz; Rodrigues, Ana Lúcia S

2013-09-15

Glutathione (GSH) displays a broad range of functions, among them a role as a neuromodulator with some neuroprotective properties. Taking into account that oxidative stress has been associated with depressive disorders, this study investigated the possibility that GSH, a major cell antioxidant, elicits an antidepressant-like effect in mice. Thus, GSH was administered by i.c.v. route to mice that were tested in the forced swimming test and in the tail suspension test, two predictive tests for antidepressant drug activity. In addition, GSH metabolism and the redox environment were modulated in order to study the possible mechanisms underlying the effects of GSH in the forced swimming test. The administration of GSH decreased the immobility time in the forced swimming test (300-3000nmol/site) and tail suspension test (100-1000nmol/site), consistent with an antidepressant-like effect. GSH depletion elicited by l-buthionine sulfoximine (3.2μmol/site, i.c.v.) did not alter the antidepressant-like effect of GSH, whereas the inhibition of extracellular GSH catabolism by acivicin (100nmol/site, i.c.v.) prevented the antidepressant-like effect of GSH. Moreover, a sub-effective dose (0.01nmol/site, i.c.v.) of the oxidizing agent DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) potentiated the effect of GSH (100nmol/site, i.c.v.), while the pretreatment (25-100mg/kg, i.p.) with the reducing agent DTT (dl-dithiothreitol) prevented the antidepressant-like effect of GSH (300nmol/site, i.c.v.). DTNB (0.1nmol/site, i.c.v.), produced an antidepressant-like effect, per se, which was abolished by DTT (25mg/kg, i.p.). The results show, for the first time, that centrally administered GSH produces an antidepressant-like effect in mice, which can be modulated by the GSH metabolism and the thiol/disulfide reagents. The redox environment may constitute a new venue for future antidepressant-drug development. Copyright © 2013 Elsevier B.V. All rights reserved.

Redox, iron, and nutritional status of children during swimming training.

Science.gov (United States)

Kabasakalis, Athanasios; Kalitsis, Konstantinos; Nikolaidis, Michalis G; Tsalis, George; Kouretas, Dimitris; Loupos, Dimitris; Mougios, Vassilis

2009-11-01

Effects of exercise training on important determinants of children's long-term health, such as redox and iron status, have not been adequately investigated. The aim of the present study was to examine changes in markers of the redox, iron and nutritional status of boy and girl swimmers during a prolonged period of training. 11 boys and 13 girls, aged 10-11 years, were members of a swimming club. They were assessed at the beginning of the training season, at 13 weeks and at 23 weeks through blood sampling and recording of the diet. Reduced glutathione increased at 13 and 23 weeks, whereas oxidised glutathione decreased at 13 weeks, resulting in an increase of the reduced/oxidised glutathione ratio at 13 and 23 weeks. Total antioxidant capacity, catalase, thiobarbituric acid-reactive substances, hemoglobin, transferrin saturation and ferritin did not change significantly. Carbohydrate intake was below 50% of energy and fat intake was above 40% of energy. Intakes of saturated fatty acids and cholesterol were excessive. Iron intake was adequate but intakes of folate, vitamin E, calcium and magnesium did not meet the recommended daily allowances. No significant differences were found between sexes in any of the parameters measured. In conclusion, child swimmers improved the redox status of glutathione during training, although the intake of antioxidant nutrients did not change. The iron status was not impaired by training. Suboptimal intake of several nutrients suggests the need for nutritional monitoring and education of children athletes.

Fe-phyllosilicate redox cycling organisms from a redox transition zone in Hanford 300 Area sediments

Directory of Open Access Journals (Sweden)

Jason eBenzine

2013-12-01

Full Text Available Microorganisms capable of reducing or oxidizing structural iron (Fe in Fe-bearing phyllosilicate minerals were enriched and isolated from a subsurface redox transition zone at the Hanford 300 Area site in eastern Washington, USA. Both conventional and in situ i-chip enrichment strategies were employed. One Fe(III-reducing Geobacter (G. bremensis strain R1, Deltaproteobacteria and six Fe(II phyllosilicate-oxidizing isolates from the Alphaproteobacteria (Bradyrhizobium japonicum strains 22, is5, and in8p8, Betaproteobacteria (Cupriavidus necator strain A5-1, Dechloromonas agitata strain is5, and Actinobacteria (Nocardioides sp. strain in31 were recovered. The G. bremensis isolate grew by oxidizing acetate with the oxidized form of NAu-2 smectite as the electron acceptor. The Fe(II-oxidizers grew by oxidation of chemically reduced smectite as the energy source with nitrate as the electron acceptor. The Bradyrhizobium isolates could also carry out aerobic oxidation of biotite. This is the first report of the recovery of a Fe(II-oxidizing Nocardioides, and to date only one other Fe(II-oxidizing Bradyrhizobium is known. The 16S rRNA gene sequences of the isolates were similar to ones found in clone libraries from Hanford 300 sediments and groundwater, suggesting that such organisms may be present and active in situ. Whole genome sequencing of the isolates is underway, the results of which will enable comparative genomic analysis of mechanisms of extracellular phyllosilicate Fe redox metabolism, and facilitate development of techniques to detect the presence and expression of genes associated with microbial phyllosilicate Fe redox cycling in sediments.

Ex-situ tracking solid oxide cell electrode microstructural evolution in a redox cycle by high resolution ptychographic nanotomography

DEFF Research Database (Denmark)

De Angelis, Salvatore; Jørgensen, Peter Stanley; Esposito, Vincenzo

2017-01-01

, the nickel and pore networks undergo major reorganization and the formation of internal voids is observed in the nickel-oxide particles after the oxidation. These observations are discussed in terms of reaction kinetics, electrode mechanical stress and the consequences of redox cycling on electrode...... towards this aim by visualizing a complete redox cycle in a solid oxide cell (SOC) electrode. The experiment demonstrates synchrotron-based ptychography as a method of imaging SOC electrodes, providing an unprecedented combination of 3D image quality and spatial resolution among non-destructive imaging...

Perylene-Based All-Organic Redox Battery with Excellent Cycling Stability.

Science.gov (United States)

Iordache, Adriana; Delhorbe, Virginie; Bardet, Michel; Dubois, Lionel; Gutel, Thibaut; Picard, Lionel

2016-09-07

Organic materials derived from biomass can constitute a viable option as replacements for inorganic materials in lithium-ion battery electrodes owing to their low production costs, recyclability, and structural diversity. Among them, conjugated carbonyls have become the most promising type of organic electrode material as they present high theoretical capacity, fast reaction kinetics, and quasi-infinite structural diversity. In this letter, we report a new perylene-based all-organic redox battery comprising two aromatic conjugated carbonyl electrode materials, the prelithiated tetra-lithium perylene-3,4,9,10-tetracarboxylate (PTCLi6) as negative electrode material and the poly(N-n-hexyl-3,4,9,10-perylene tetracarboxylic)imide (PTCI) as positive electrode material. The resulting battery shows promising long-term cycling stability up to 200 cycles. In view of the enhanced cycling performances, the two organic materials studied herein are proposed as suitable candidates for the development of new all-organic lithium-ion batteries.

Isolation of phyllosilicate-iron redox cycling microorganisms from an illite-smectite rich hydromorphic soil.

Science.gov (United States)

Shelobolina, Evgenya; Konishi, Hiromi; Xu, Huifang; Benzine, Jason; Xiong, Mai Yia; Wu, Tao; Blöthe, Marco; Roden, Eric

2012-01-01

The biogeochemistry of phyllosilicate-Fe redox cycling was studied in a Phalaris arundinacea (reed canary grass) dominated redoximorphic soil from Shovelers Sink, a small glacial depression near Madison, WI. The clay size fraction of Shovelers Sink soil accounts for 16% of the dry weight of the soil, yet contributes 74% of total Fe. The dominant mineral in the clay size fraction is mixed layer illite-smectite, and in contrast to many other soils and sediments, Fe(III) oxides are present in low abundance. We examined the Fe biogeochemistry of Shovelers Sink soils, estimated the abundance of Fe redox cycling microorganisms, and isolated in pure culture representative phyllosilicate-Fe oxidizing and reducing organisms. The abundance of phyllosilicate-Fe reducing and oxidizing organisms was low compared to culturable aerobic heterotrophs. Both direct isolation and dilution-to-extinction approaches using structural Fe(II) in Bancroft biotite as a Fe(II) source, and O(2) as the electron acceptor, resulted in recovery of common rhizosphere organisms including Bradyrhizobium spp. and strains of Cupriavidus necator and Ralstonia solanacearum. In addition to oxidizing biotite and soluble Fe(II) with O(2), each of these isolates was able to oxidize Fe(II) in reduced NAu-2 smectite with [Formula: see text] as the electron acceptor. Oxidized NAu-2 smectite or amorphous Fe(III) oxide served as electron acceptors for enrichment and isolation of Fe(III)-reducing microorganisms, resulting in recovery of a strain related to Geobacter toluenoxydans. The ability of the recovered microorganisms to cycle phyllosilicate-Fe was verified in an experiment with native Shovelers Sink clay. This study confirms that Fe in the native Shovelers Sink clay is readily available for microbial redox transformation and can be cycled by the Fe(III)-reducing and Fe(II)-oxidizing microorganisms recovered from the soil.

Isolation of Phyllosilicate–Iron Redox Cycling Microorganisms from an Illite–Smectite Rich Hydromorphic Soil

Science.gov (United States)

Shelobolina, Evgenya; Konishi, Hiromi; Xu, Huifang; Benzine, Jason; Xiong, Mai Yia; Wu, Tao; Blöthe, Marco; Roden, Eric

2012-01-01

The biogeochemistry of phyllosilicate–Fe redox cycling was studied in a Phalaris arundinacea (reed canary grass) dominated redoximorphic soil from Shovelers Sink, a small glacial depression near Madison, WI. The clay size fraction of Shovelers Sink soil accounts for 16% of the dry weight of the soil, yet contributes 74% of total Fe. The dominant mineral in the clay size fraction is mixed layer illite–smectite, and in contrast to many other soils and sediments, Fe(III) oxides are present in low abundance. We examined the Fe biogeochemistry of Shovelers Sink soils, estimated the abundance of Fe redox cycling microorganisms, and isolated in pure culture representative phyllosilicate–Fe oxidizing and reducing organisms. The abundance of phyllosilicate–Fe reducing and oxidizing organisms was low compared to culturable aerobic heterotrophs. Both direct isolation and dilution-to-extinction approaches using structural Fe(II) in Bancroft biotite as a Fe(II) source, and O2 as the electron acceptor, resulted in recovery of common rhizosphere organisms including Bradyrhizobium spp. and strains of Cupriavidus necator and Ralstonia solanacearum. In addition to oxidizing biotite and soluble Fe(II) with O2, each of these isolates was able to oxidize Fe(II) in reduced NAu-2 smectite with NO3- as the electron acceptor. Oxidized NAu-2 smectite or amorphous Fe(III) oxide served as electron acceptors for enrichment and isolation of Fe(III)-reducing microorganisms, resulting in recovery of a strain related to Geobacter toluenoxydans. The ability of the recovered microorganisms to cycle phyllosilicate–Fe was verified in an experiment with native Shovelers Sink clay. This study confirms that Fe in the native Shovelers Sink clay is readily available for microbial redox transformation and can be cycled by the Fe(III)-reducing and Fe(II)-oxidizing microorganisms recovered from the soil. PMID:22493596

Glutathione oxidation correlates with one-lung ventilation time and PO2/FiO2 ratio during pulmonary lobectomy.

Science.gov (United States)

García-de-la-Asunción, José; García-Del-Olmo, Eva; Galan, Genaro; Guijarro, Ricardo; Martí, Francisco; Badenes, Rafael; Perez-Griera, Jaume; Duca, Alejandro; Delgado, Carlos; Carbonell, Jose; Belda, Javier

2016-09-01

During lung lobectomy, the operated lung completely collapses with simultaneous hypoxic pulmonary vasoconstriction, followed by expansion and reperfusion. Here, we investigated glutathione oxidation and lipoperoxidation in patients undergoing lung lobectomy, during one-lung ventilation (OLV) and after resuming two-lung ventilation (TLV), and examined the relationship with OLV duration. We performed a single-centre, observational, prospective study in 32 patients undergoing lung lobectomy. Blood samples were collected at five time-points: T0, pre-operatively; T1, during OLV, 5 minutes before resuming TLV; and T2, T3, and T4, respectively, 5, 60, and 180 minutes after resuming TLV. Samples were tested for reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione redox potential, and malondialdehyde (MDA). GSSG and MDA blood levels increased at T1, and increased further at T2. OLV duration directly correlated with marker levels at T1 and T2. Blood levels of GSH and glutathione redox potential decreased at T1-T3. GSSG, oxidized glutathione/total glutathione ratio, and MDA levels were inversely correlated with arterial blood PO2/FiO2 at T1 and T2. During lung lobectomy and OLV, glutathione oxidation, and lipoperoxidation marker blood levels increase, with further increases after resuming TLV. Oxidative stress degree was directly correlated with OLV duration, and inversely correlated with arterial blood PO2/FiO2.

All-oxide Raman-active traps for light and matter: probing redox homeostasis model reactions in aqueous environment.

Science.gov (United States)

Alessandri, Ivano; Depero, L E

2014-04-09

Core-shell colloidal crystals can act as very efficient traps for light and analytes. Here it is shown that Raman-active probes can be achieved using SiO2-TiO2 core-shell beads. These systems are successfully tested in monitoring of glutathione redox cycle at physiological concentration in aqueous environment, without need of any interfering enhancers. These materials represent a promising alternative to conventional, metal-based SERS probes for investigating chemical and biochemical reactions under real working conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron chemistry of Hawaiian rainforest soil solution: Biogeochemical implications of multiple Fe redox cycles

Science.gov (United States)

Thompson, A.; Chorover, J.; Chadwick, O.

2003-12-01

Iron (Fe)-oxides are important sorbents for nutrients, pollutants and natural organic matter (NOM). When flucutations in soil oxygen status exist, Fe can cycle through reduced and oxidized forms and thus greatly affect the aqueous conc. of nutrients and metals. We are examining the influence of oscillating oxic/anoxic conditions on Fe-oxide formation and biogeochemical processes (microbial community composition, and carbon, nutrient and trace metal availability). Our work makes use of a natural rainfall gradient ranging from 2.2 to 4.2 m mean annual precipitation (MAP) on the island of Maui, Hawaii, USA. All sites developed on a 400ky basaltic lava flow and comprise soils under similar vegetation. Solid phase Fe concentration and oxidation state vary systematically across this rainfall gradient with a sharp decrease in pedogenic Fe between 2.8 m and 3.5 m MAP that corresponds with an Eh of 330 mV (1-yr ave.). Fe isotopic composition and Fe-oxide associated rare earth elements (REE) also suggest a shift from ligand-promoted to redutive Fe dissolution with increasing rainfall. To examine the effects of multiple Fe oxidation/reduction cycles, we constructed a set of redox-stat reactors that maintain Eh values within a set range by small Eh-triggered additions of oxygen. Triplicate soil slurry reactors are subjected to redox (Eh) oscillations such that Fe is repeatedly cycled from oxidized to reduced forms. During our current experiment, we measure pH and Eh dynamics and monitor the distribution of Fe(II) and Fe(III), major ion and anion concentrations, a range of trace metals including the REE, and total organic carbon (TOC) in three Stokes-effective particle size fractions (DNA fingerprinting is used to track changes in the microbial community. Prior to implementing the rigorous sampling procedure above, we completed two preliminary reactor experiments focusing only on Fe distribution between aqueous, HCl, and oxalate extractions. These experiments illustrated (1) a

Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor.

Science.gov (United States)

Fan, Yichong; Makar, Merna; Wang, Michael X; Ai, Hui-Wang

2017-09-01

Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system. In this work, we developed the first genetically encoded fluorescent biosensor for Trx redox by engineering a redox relay between the active-site cysteines of human Trx1 and rxRFP1, a redox-sensitive red fluorescent protein. We used the resultant biosensor-TrxRFP1-to selectively monitor perturbations of Trx redox in various mammalian cell lines. We subcellularly localized TrxRFP1 to image compartmentalized Trx redox changes. We further combined TrxRFP1 with a green fluorescent Grx1-roGFP2 biosensor to simultaneously monitor Trx and glutathione redox dynamics in live cells in response to chemical and physiologically relevant stimuli.

Glutathione-dependent responses of plants to drought: a review

Directory of Open Access Journals (Sweden)

Mateusz Labudda

2014-02-01

Full Text Available Water is a renewable resource. However, with the human population growth, economic development and improved living standards, the world’s supply of fresh water is steadily decreasing and consequently water resources for agricultural production are limited and diminishing. Water deficiency is a significant problem in agriculture and increasing efforts are currently being made to understand plant tolerance mechanisms and to develop new tools (especially molecular that could underpin plant breeding and cultivation. However, the biochemical and molecular mechanisms of plant water deficit tolerance are not fully understood, and the data available is incomplete. Here, we review the significance of glutathione and its related enzymes in plant responses to drought. Firstly, the roles of reduced glutathione and reduced/oxidized glutathione ratio, are discussed, followed by an extensive discussion of glutathione related enzymes, which play an important role in plant responses to drought. Special attention is given to the S-glutathionylation of proteins, which is involved in cell metabolism regulation and redox signaling in photosynthetic organisms subjected to abiotic stress. The review concludes with a brief overview of future perspectives for the involvement of glutathione and related enzymes in drought stress responses.

Suppression of External NADPH Dehydrogenase—NDB1 in Arabidopsis thaliana Confers Improved Tolerance to Ammonium Toxicity via Efficient Glutathione/Redox Metabolism

Science.gov (United States)

Podgórska, Anna; Borysiuk, Klaudia; Tarnowska, Agata; Jakubiak, Monika; Burian, Maria; Rasmusson, Allan G.

2018-01-01

Environmental stresses, including ammonium (NH4+) nourishment, can damage key mitochondrial components through the production of surplus reactive oxygen species (ROS) in the mitochondrial electron transport chain. However, alternative electron pathways are significant for efficient reductant dissipation in mitochondria during ammonium nutrition. The aim of this study was to define the role of external NADPH-dehydrogenase (NDB1) during oxidative metabolism of NH4+-fed plants. Most plant species grown with NH4+ as the sole nitrogen source experience a condition known as “ammonium toxicity syndrome”. Surprisingly, transgenic Arabidopsis thaliana plants suppressing NDB1 were more resistant to NH4+ treatment. The NDB1 knock-down line was characterized by milder oxidative stress symptoms in plant tissues when supplied with NH4+. Mitochondrial ROS accumulation, in particular, was attenuated in the NDB1 knock-down plants during NH4+ treatment. Enhanced antioxidant defense, primarily concerning the glutathione pool, may prevent ROS accumulation in NH4+-grown NDB1-suppressing plants. We found that induction of glutathione peroxidase-like enzymes and peroxiredoxins in the NDB1-surpressing line contributed to lower ammonium-toxicity stress. The major conclusion of this study was that NDB1 suppression in plants confers tolerance to changes in redox homeostasis that occur in response to prolonged ammonium nutrition, causing cross tolerance among plants. PMID:29747392

The role of copper and oxalate in the redox cycling of iron in atmospheric waters

Science.gov (United States)

Sedlak, David L.; Hoigné, Jürg

During daytime, the redox cycling of dissolved iron compounds in atmospheric waters, and the related in-cloud transformations of photooxidants, are affected by reactions of Fe and Cu with hydroperoxy (HO 2) and superoxide (O 2-) radicals and the photoreduction of Fe(III)-oxalato complexes. We have investigated several of the important chemical reactions in this redox cycle, through laboratory simulation of the system, using γ-radiation to produce HO 2/O 2-. At concentrations comparable to those measured in atmospheric waters, the redox cycling of Fe was dramatically affected by the presence of oxalate and trace concentrations of Cu. At concentrations more than a hundred times lower than Fe, Cu consumed most of the HO 2/O 2-, and cycled between the Cu(II) and Cu(I) forms. Cu + reacted with FeOH 2+ to produce Fe(II) and Cu(II), with a second order rate constant of approximately 3 × 10 7 M -1s -1. The presence of oxalate resulted in the formation of Fe(III)-oxalato complexes that were essentially unreactive with HO 2/O 2-. Only at high oxalate concentrations was the Fe(II)C 2O 4 complex also formed, and it reacted relatively rapidly with hydrogen peroxide ( k = (3.1 ± 0.6) × 10 4 M -1s -1). Simulations incorporating measurements for other redox mechanisms, including oxidation by ozone, indicate that, during daytime, Fe should be found mostly in the ferrous oxidation state, and that reactions of FeOH 2+ with Cu(I) and HO 2/O 2-, and to a lesser degree, the photolysis of Fe(III)-oxalato complexes, are important mechanisms of Fe reduction in atmospheric waters. The catalytic effect of Cu(II)/Cu(I) and Fe(III)/Fe(II) should also significantly increase the sink function of the atmospheric liquid phase for HO 2 present in a cloud. A simple kinetic model for the reactions of Fe, Cu and HO 2/O 2-, accurately predicted the changes in Fe oxidation states that occurred when authentic fogwater samples were exposed to HO 2/O 2-.

Ni-YSZ solid oxide fuel cell anode behavior upon redox cycling based on electrical characterization

DEFF Research Database (Denmark)

Klemensø, Trine; Mogensen, Mogens Bjerg

2007-01-01

Nickel (Ni)—yttria-stabilized zirconia (YSZ) cermets are a prevalent material used for solid oxide fuel cells. The cermet degrades upon redox cycling. The degradation is related to microstructural changes, but knowledge of the mechanisms has been limited. Direct current conductivity measurements...

Arabidopsis redox status in response to caterpillar herbivory

Directory of Open Access Journals (Sweden)

Jamuna ePaudel

2013-05-01

Full Text Available Plant responses to insect herbivory are regulated through complex, hormone-mediated interactions. Some caterpillar species have evolved strategies to manipulate this system by inducing specific pathways that suppress plant defense responses. Effectors in the labial saliva (LS secretions of Spodoptera exigua caterpillars are believed to induce the salicylic acid (SA pathway to interfere with the jasmonic acid (JA defense pathway; however, the mechanism underlying this subversion is unknown. Since Noctuid caterpillar LS contains enzymes that may affect cellular redox balance, this study investigated rapid changes in cellular redox metabolites within 45 min after herbivory. Caterpillar LS is involved in suppressing the increase in oxidative stress that was observed in plants fed upon by caterpillars with impaired LS secretions. To further understand the link between cellular redox balance and plant defense responses, marker genes of SA, JA and ethylene (ET pathways were compared in wildtype, the glutathione-compromised pad2-1 mutant and the tga2/5/6 triple mutant plants. AtPR1 and AtPDF1.2 showed LS-dependent expression that was alleviated in the pad2-1 and tga2/5/6 triple mutants. In comparison, the ET-dependent genes ERF1 expression showed LS-associated changes in both wildtype and pad2-1 mutant plants and the ORA 59 marker AtHEL had increased expression in response to herbivory, but a LS-dependent difference was not noted. These data support the model that there are SA/NPR1-, glutathione-dependent and ET-, glutathione-independent mechanisms leading to LS-associated suppression of plant induced defences.

Nitric Oxide Ameliorates Zinc Oxide Nanoparticles Phytotoxicity in Wheat Seedlings: Implication of the Ascorbate–Glutathione Cycle

Science.gov (United States)

Tripathi, Durgesh K.; Mishra, Rohit K.; Singh, Swati; Singh, Samiksha; Vishwakarma, Kanchan; Sharma, Shivesh; Singh, Vijay P.; Singh, Prashant K.; Prasad, Sheo M.; Dubey, Nawal K.; Pandey, Avinash C.; Sahi, Shivendra; Chauhan, Devendra K.

2017-01-01

The present study investigates ameliorative effects of nitric oxide (NO) against zinc oxide nanoparticles (ZnONPs) phytotoxicity in wheat seedlings. ZnONPs exposure hampered growth of wheat seedlings, which coincided with reduced photosynthetic efficiency (Fv/Fm and qP), due to increased accumulation of zinc (Zn) in xylem and phloem saps. However, SNP supplementation partially mitigated the ZnONPs-mediated toxicity through the modulation of photosynthetic activity and Zn accumulation in xylem and phloem saps. Further, the results reveal that ZnONPs treatments enhanced levels of hydrogen peroxide and lipid peroxidation (as malondialdehyde; MDA) due to severely inhibited activities of the following ascorbate–glutatione cycle (AsA–GSH) enzymes: ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase, and its associated metabolites ascorbate and glutathione. In contrast to this, the addition of SNP together with ZnONPs maintained the cellular functioning of the AsA–GSH cycle properly, hence lesser damage was noticed in comparison to ZnONPs treatments alone. The protective effect of SNP against ZnONPs toxicity on fresh weight (growth) can be reversed by 2-(4carboxy-2-phenyl)-4,4,5,5-tetramethyl- imidazoline-1-oxyl-3-oxide, a NO scavenger, and thus suggesting that NO released from SNP ameliorates ZnONPs toxicity. Overall, the results of the present study have shown the role of NO in the reducing of ZnONPs toxicity through the regulation of accumulation of Zn as well as the functioning of the AsA–GSH cycle. PMID:28220127

Long-Cycling Aqueous Organic Redox Flow Battery (AORFB) toward Sustainable and Safe Energy Storage.

Science.gov (United States)

Hu, Bo; DeBruler, Camden; Rhodes, Zayn; Liu, T Leo

2017-01-25

Redox flow batteries (RFBs) are a viable technology to store renewable energy in the form of electricity that can be supplied to electricity grids. However, widespread implementation of traditional RFBs, such as vanadium and Zn-Br 2 RFBs, is limited due to a number of challenges related to materials, including low abundance and high costs of redox-active metals, expensive separators, active material crossover, and corrosive and hazardous electrolytes. To address these challenges, we demonstrate a neutral aqueous organic redox flow battery (AORFB) technology utilizing a newly designed cathode electrolyte containing a highly water-soluble ferrocene molecule. Specifically, water-soluble (ferrocenylmethyl)trimethylammonium chloride (FcNCl, 4.0 M in H 2 O, 107.2 Ah/L, and 3.0 M in 2.0 NaCl, 80.4 Ah/L) and N 1 -ferrocenylmethyl-N 1 ,N 1 ,N 2 ,N 2 ,N 2 -pentamethylpropane-1,2-diaminium dibromide, (FcN 2 Br 2 , 3.1 M in H 2 O, 83.1 Ah/L, and 2.0 M in 2.0 M NaCl, 53.5 Ah/L) were synthesized through structural decoration of hydrophobic ferrocene with synergetic hydrophilic functionalities including an ammonium cation group and a halide anion. When paired with methyl viologen (MV) as an anolyte, resulting FcNCl/MV and FcN 2 Br 2 /MV AORFBs were operated in noncorrosive neutral NaCl supporting electrolytes using a low-cost anion-exchange membrane. These ferrocene/MV AORFBs are characterized as having high theoretical energy density (45.5 Wh/L) and excellent cycling performance from 40 to 100 mA/cm 2 . Notably, the FcNCl/MV AORFBs (demonstrated at 7.0 and 9.9 Wh/L) exhibited unprecedented long cycling performance, 700 cycles at 60 mA/cm 2 with 99.99% capacity retention per cycle, and delivered power density up to 125 mW/cm 2 . These AORFBs are built from earth-abundant elements and are environmentally benign, thus representing a promising choice for sustainable and safe energy storage.

Ni-YSZ solid oxide fuel cell anode behavior upon redox cycling based on electrical characterization

DEFF Research Database (Denmark)

Klemensø, Trine; Mogensen, Mogens Bjerg

2006-01-01

Ni-YSZ cermets are a prevalent material used for solid oxide fuel cells. However, the cermet degrades upon redox cycling. The degradation is related to microstructural changes, but knowledge of the mechanisms has been limited. DC conductivity measurements were performed on cermets and cermets...

Expression Patterns of Genes Involved in Ascorbate-Glutathione Cycle in Aphid-Infested Maize (Zea mays L.) Seedlings.

Science.gov (United States)

Sytykiewicz, Hubert

2016-02-23

Reduced forms of ascorbate (AsA) and glutathione (GSH) are among the most important non-enzymatic foliar antioxidants in maize (Zea mays L.). The survey was aimed to evaluate impact of bird cherry-oat aphid (Rhopalosiphum padi L.) or grain aphid (Sitobion avenae F.) herbivory on expression of genes related to ascorbate-glutathione (AsA-GSH) cycle in seedlings of six maize varieties (Ambrozja, Nana, Tasty Sweet, Touran, Waza, Złota Karłowa), differing in resistance to the cereal aphids. Relative expression of sixteen maize genes encoding isoenzymes of ascorbate peroxidase (APX1, APX2, APX3, APX4, APX5, APX6, APX7), monodehydroascorbate reductase (MDHAR1, MDHAR2, MDHAR3, MDHAR4), dehydroascorbate reductase (DHAR1, DHAR2, DHAR3) and glutathione reductase (GR1, GR2) was quantified. Furthermore, effect of hemipterans' attack on activity of APX, MDHAR, DHAR and GR enzymes, and the content of reduced and oxidized ascorbate and glutathione in maize plants were assessed. Seedling leaves of more resistant Z. mays varieties responded higher elevations in abundance of target transcripts. In addition, earlier and stronger aphid-triggered changes in activity of APX, MDHAR, DHAR and GR enzymes, and greater modulations in amount of the analyzed antioxidative metabolites were detected in foliar tissues of highly resistant Ambrozja genotype in relation to susceptible Tasty Sweet plants.

The interplay between sulphur and selenium metabolism influences the intracellular redox balance in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Mapelli, Valeria; Hillestrøm, Peter René; Patil, Kalpesh

2012-01-01

oxidative stress response is active when yeast actively metabolizes Se, and this response is linked to the generation of intracellular redox imbalance. The redox imbalance derives from a disproportionate ratio between the reduced and oxidized forms of glutathione and also from the influence of Se metabolism...

The Redox Proteome*

Science.gov (United States)

Go, Young-Mi; Jones, Dean P.

2013-01-01

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437

Importance of glutamine metabolism in leukemia cells by energy production through TCA cycle and by redox homeostasis.

Science.gov (United States)

Goto, Mineaki; Miwa, Hiroshi; Shikami, Masato; Tsunekawa-Imai, Norikazu; Suganuma, Kazuto; Mizuno, Shohei; Takahashi, Miyuki; Mizutani, Motonori; Hanamura, Ichiro; Nitta, Masakazu

2014-07-01

Some cancer cells depend on glutamine despite of pronounced glycolysis. We examined the glutamine metabolism in leukemia cells, and found that HL-60 cells most depended on glutamine in the 4 acute myelogenous leukemia (AML) cell lines examined: growth of HL-60 cells was most suppressed by glutamine deprivation and by inhibition of glutaminolysis, which was rescued by tricarboxylic acid (TCA) cycle intermediate, oxaloacetic acid. Glutamine is also involved in antioxidant defense function by increasing glutathione. Glutamine deprivation suppressed the glutathione content and elevated reactive oxygen species most evidently in HL-60 cells. Glutamine metabolism might be a therapeutic target in some leukemia.

Beyond the Fe-P-redox connection: preferential regeneration of phosphorus from organic matter as a key control on Baltic Sea nutrient cycles

NARCIS (Netherlands)

Jilbert, T.; Slomp, C.P.; Gustafsson, B.G.; Boer, W.

2011-01-01

Patterns of regeneration and burial of phosphorus (P) in the Baltic Sea are strongly dependent on redox conditions. Redox varies spatially along water depth gradients and temporally in response to the seasonal cycle and multidecadal hydrographic variability. Alongside the welldocumented link

Integration of the thiol redox status with cytokine response to physical training in professional basketball players.

Science.gov (United States)

Zembron-Lacny, A; Slowinska-Lisowska, M; Ziemba, A

2010-01-01

The present study was designed to evaluate the plasma markers of reactive oxygen species (ROS) activity and cytokines, and their relationship with thiol redox status of basketball players during training. Sixteen professional players of the Polish Basketball Extraleague participated in the study. The study was performed during the preparatory period and the play-off round. Markers of ROS activity (lipid peroxidation TBARS, protein carbonylation PC) and reduced glutathione (GSH) demonstrated regularity over time, i.e. TBARS, PC and GSH were elevated at the beginning and decreased at the end of training periods. Oxidized glutathione (GSSG) was not affected by exercise training. Thiol redox status (GSH(total)-2GSSG/GSSG) correlated with TBARS and PC in both training periods. The level of interleukin-6 (IL-6) was increased and positively correlated with thiol redox (r=0.423) in the preparatory period, whereas tumor necrosis factor alpha (TNFalpha) was increased and inversely correlated with thiol redox (r= 0.509) in the play-off round. The present study showed significant shifts in markers of ROS activity, thiol redox status and inflammatory mediators (IL-6, TNFalpha) following professional sport training as well as correlation between changes in thiol redox and cytokine response.

Redox potential and mobility of contaminant oxyanions (As, Sb, Cr) in argillaceous rock subjected to oxic and anoxic cycles

International Nuclear Information System (INIS)

Markelova, Ekaterina

2016-01-01

Electron transfer (redox) reactions are key processes in the biogeochemical functioning of natural systems. Redox reactions control the speciation and mobility of major elements (e.g., carbon, nitrogen, iron, and manganese) and environmentally important contaminants such as arsenic (As), antimony (Sb), and chromium (Cr). Nonetheless, the characterization of redox conditions and their effects on biogeochemical cycling and contaminant fate remain incompletely understood. The first part of this thesis focused on the interpretation of redox potential (EH) measurements using results obtained in synthetic biogeochemical systems of increasing complexity under dynamic, redox-oscillating conditions. By progressively combining inorganic solutes, an organic electron donor (lactate), an aqueous electron acceptor (nitrate), a metabolically versatile heterotrophic bacterium (Shewanella oneidensis), and a solid-state electron acceptor (goethite), a full redox cascade from +500 to -350 mV (pH ∼7.4) was reproduced in the laboratory. The experimental results revealed that a conventional Pt redox electrode responds to a variety of physical, chemical, and microbial factors. In particular, the presence of the bacteria always led to lower EH readings. In contrast, measurements of EH in argillaceous suspensions were insensitive to changes in chemical ratios of the redox-sensitive, but non-electro-active, couples, including O 2 /H 2 O, CrO 4 2- /Cr(OH) 3 , NO 3 - /NO 2 - /NH 4 + , HAsO 4 2- /H3AsO 3 , and Sb(OH) 6 - /Sb 2 O 3 . Therefore, EH measurements are shown to have limited usefulness in the natural systems depleted in electro-active redox couples, such as α-FeOOH(s)/Fe 2+ (aq). The second part of the thesis focused on the behavior of oxy-anion contaminants under redox-oscillating conditions in the argillaceous subsoil suspensions. Successive cycles of oxic and anoxic conditions were imposed on the argillaceous suspensions amended with a mixture of oxidized Cr(VI), As(V), Sb

The Redox Code.

Science.gov (United States)

Jones, Dean P; Sies, Helmut

2015-09-20

The redox code is a set of principles that defines the positioning of the nicotinamide adenine dinucleotide (NAD, NADP) and thiol/disulfide and other redox systems as well as the thiol redox proteome in space and time in biological systems. The code is richly elaborated in an oxygen-dependent life, where activation/deactivation cycles involving O₂ and H₂O₂ contribute to spatiotemporal organization for differentiation, development, and adaptation to the environment. Disruption of this organizational structure during oxidative stress represents a fundamental mechanism in system failure and disease. Methodology in assessing components of the redox code under physiological conditions has progressed, permitting insight into spatiotemporal organization and allowing for identification of redox partners in redox proteomics and redox metabolomics. Complexity of redox networks and redox regulation is being revealed step by step, yet much still needs to be learned. Detailed knowledge of the molecular patterns generated from the principles of the redox code under defined physiological or pathological conditions in cells and organs will contribute to understanding the redox component in health and disease. Ultimately, there will be a scientific basis to a modern redox medicine.

The level of menadione redox-cycling in pancreatic β-cells is proportional to the glucose concentration: Role of NADH and consequences for insulin secretion

Energy Technology Data Exchange (ETDEWEB)

Heart, Emma [Cellular Dynamics Program, Marine Biological Laboratory, Woods Hole, MA, 02543 (United States); Palo, Meridith; Womack, Trayce [Department of Science, United States Coast Guard Academy, New London, CT, 06320 (United States); Smith, Peter J.S. [Cellular Dynamics Program, Marine Biological Laboratory, Woods Hole, MA, 02543 (United States); Institute for Life Sciences, University of Southampton (United Kingdom); Gray, Joshua P., E-mail: Joshua.p.gray@uscga.edu [Cellular Dynamics Program, Marine Biological Laboratory, Woods Hole, MA, 02543 (United States); Department of Science, United States Coast Guard Academy, New London, CT, 06320 (United States)

2012-01-15

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4–7 mM) to stimulatory (8–16 mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H{sub 2}O{sub 2}), a newly recognized coupling factor linking glucose metabolism to insulin secretion. However, high and toxic levels of H{sub 2}O{sub 2} inhibit insulin secretion. Menadione, which produces H{sub 2}O{sub 2} via redox cycling mechanism in a dose-dependent manner, was investigated for its effect on β-cell metabolism and insulin secretion in INS-1 832/13, a rat β-cell insulinoma cell line, and primary rodent islets. Menadione-dependent redox cycling and resulting H{sub 2}O{sub 2} production under stimulatory glucose exceeded several-fold those reached at basal glucose. This was paralleled by a differential effect of menadione (0.1–10 μM) on insulin secretion, which was enhanced at basal, but inhibited at stimulatory glucose. Redox cycling of menadione and H{sub 2}O{sub 2} formation was dependent on glycolytically-derived NADH, as inhibition of glycolysis and application of non-glycogenic insulin secretagogues did not support redox cycling. In addition, activity of plasma membrane electron transport, a system dependent in part on glycolytically-derived NADH, was also inhibited by menadione. Menadione-dependent redox cycling was sensitive to the NQO1 inhibitor dicoumarol and the flavoprotein inhibitor diphenylene iodonium, suggesting a role for NQO1 and other oxidoreductases in this process. These data may explain the apparent dichotomy between the stimulatory and inhibitory effects of H{sub 2}O{sub 2} and menadione on insulin secretion. -- Highlights: ► Menadione stimulation or inhibition of insulin secretion is dependent upon applied glucose levels. ► Menadione-dependent H{sub 2}O{sub 2} production is proportional to applied glucose levels. ► Quinone-mediated redox cycling

The level of menadione redox-cycling in pancreatic β-cells is proportional to the glucose concentration: Role of NADH and consequences for insulin secretion

International Nuclear Information System (INIS)

Heart, Emma; Palo, Meridith; Womack, Trayce; Smith, Peter J.S.; Gray, Joshua P.

2012-01-01

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4–7 mM) to stimulatory (8–16 mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H 2 O 2 ), a newly recognized coupling factor linking glucose metabolism to insulin secretion. However, high and toxic levels of H 2 O 2 inhibit insulin secretion. Menadione, which produces H 2 O 2 via redox cycling mechanism in a dose-dependent manner, was investigated for its effect on β-cell metabolism and insulin secretion in INS-1 832/13, a rat β-cell insulinoma cell line, and primary rodent islets. Menadione-dependent redox cycling and resulting H 2 O 2 production under stimulatory glucose exceeded several-fold those reached at basal glucose. This was paralleled by a differential effect of menadione (0.1–10 μM) on insulin secretion, which was enhanced at basal, but inhibited at stimulatory glucose. Redox cycling of menadione and H 2 O 2 formation was dependent on glycolytically-derived NADH, as inhibition of glycolysis and application of non-glycogenic insulin secretagogues did not support redox cycling. In addition, activity of plasma membrane electron transport, a system dependent in part on glycolytically-derived NADH, was also inhibited by menadione. Menadione-dependent redox cycling was sensitive to the NQO1 inhibitor dicoumarol and the flavoprotein inhibitor diphenylene iodonium, suggesting a role for NQO1 and other oxidoreductases in this process. These data may explain the apparent dichotomy between the stimulatory and inhibitory effects of H 2 O 2 and menadione on insulin secretion. -- Highlights: ► Menadione stimulation or inhibition of insulin secretion is dependent upon applied glucose levels. ► Menadione-dependent H 2 O 2 production is proportional to applied glucose levels. ► Quinone-mediated redox cycling is dependent on glycolysis

Glutathione content in sperm cells of infertile men

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R. V. Fafula

2017-04-01

Full Text Available Hyperproduction of reactive oxygen species can damage sperm cells and is considered to be one of the mechanisms of male infertility. Cell protection from the damaging effects of free radicals and lipid peroxidation products is generally determined by the degree of antioxidant protection. Glutathione is non-enzymatic antioxidant which plays an important protective role against oxidative damages and lipid peroxidation. The aim of the present work is to determine the content of reduced and oxidized glutathione in sperm cells of infertile men. Semen samples from 20 fertile men (normozoospermics and 72 infertile patients (12 oligozoospermics, 17 asthenozoospermics, 10 oligoasthenozoosper­mics and 33 leucocytospermic were used. The total, oxidized (GSSG and reduced (GSH glutathione levels were measured spectrophotometrically. The levels of total glutathione were significantly lower in the spermatozoa of patients with oligozoo-, asthenozoo- and oligoasthenozoospermia than in the control. Infertile groups showed significantly decreased values of reduced glutathione in sperm cells vs. fertile men, indicating an alteration of oxidative status. The oxidized glutathione levels in sperm cells of infertile men did not differ from those of normozoospermic men with proven fertility. The GSH/GSSG ratio was significantly decreased in the oligo-, astheno- and oligoasthenozoospermic groups compared to the normozoospermic group. In patients with leucocytospermia the GSH/GSSG ratio was lower but these changes were not significant. In addition, glutathione peroxidase activity in sperm cells was decreased in patients with oligozoo-, astenozoo-, oligoastenozoospermia and with leucocytospermia. The most significant changes in glutathione peroxidase activity were observed in infertile men with leucocytospermia. Decreased GSH/GSSG ratio indicates a decline in redox-potential of the glutathione system in sperm cells of men with decreased fertilizing potential

Thiol/disulfide redox states in signaling and sensing

Science.gov (United States)

Go, Young-Mi; Jones, Dean P.

2015-01-01

Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol-disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady-states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling, and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol-disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities. PMID:23356510

Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties

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Mirko eZaffagnini

2013-11-01

Full Text Available Glyceraldehyde-3-phosphate dehydrogenase (GAPDH is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively-modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively-modified GAPDH in stress signaling pathways in plants.

Role of sulfur redox cycling on arsenic mobilization in aquifers of Datong Basin, northern China

International Nuclear Information System (INIS)

Pi, Kunfu; Wang, Yanxin; Xie, Xianjun; Ma, Teng; Su, Chunli; Liu, Yaqing

2017-01-01

Sulfur redox cycling potentially exerts important influences on arsenic (As) fate in shallow groundwater systems. Hydrochemical and sediment geochemical analysis combined with thermodynamic modeling study were conducted at Datong Basin to elaborate the effects of sulfur redox cycling on As speciation and mobilization under a strongly reducing environment. Dissolved As and sulfide concentration in 32 groundwater samples with depths of 19–40 m below the land surface varied from 8 to 2700 μg/L and from <5 to 490 μg/L, respectively, while dissolved Fe(II) was relatively low ranging from <20 to 280 μg/L. The apparent co-increase in dissolved sulfide and As concentration, especially for samples with As content larger than 500 μg/L, indicates that sulfidogenesis may significantly contribute to the mobilization of As via sulfide-induced reduction of both As-bearing Fe(III) oxide minerals and As(V). Thermodynamic calculations indicate that groundwater As might be also thiolated in the presence of high-level sulfide, particularly to a large extent for As(V) speciation, instead of sequestration by As-sulfide precipitates. Results of sequential extraction and scanning electron microscopy array on sediments indicate the presence of Fe(II) sulfide mineral phases and an appreciable amount of co-existent As in the sediments, suggesting the precipitation of Fe(II) sulfides can restrict the build-up of dissolved Fe(II) and sequester As from groundwater, but not strongly enough, thereby lowering down As to a moderate level of about 500 μg/L. Thus, redox processes involving As, S and Fe species under sulfidic conditions as observed in Datong Basin not only facilitate the enrichment of As(III) species and As(V) potentially existing as thiolated species, but also the depletion of Fe(II) concentration in groundwater due to Fe(II) sulfide formation. - Highlights: • Effects of sulfur redox cycling on As enrichment were clarified in Datong. • Co-increase in aqueous As and

Thermodynamics of the oxidation-reduction reaction {2 glutathionered(aq) + NADPox(aq)=glutathioneox(aq) + NADPred(aq)}

International Nuclear Information System (INIS)

Tewari, Yadu B.; Goldberg, Robert N.

2003-01-01

Microcalorimetry, spectrophotometry, and high-performance liquid chromatography (h.p.l.c.) have been used to conduct a thermodynamic investigation of the glutathione reductase catalyzed reaction {2 glutathione red (aq) + NADP ox (aq)=glutathione ox (aq) + NADP red (aq)}. The reaction involves the breaking of a disulfide bond and is of particular importance because of the role glutathione red plays in the repair of enzymes. The measured values of the apparent equilibrium constant K ' for this reaction ranged from 0.5 to 69 and were measured over a range of temperature (288.15 K to 303.15 K), pH (6.58 to 8.68), and ionic strength I m (0.091 mol · kg -1 to 0.90 mol · kg -1 ). The results of the equilibrium and calorimetric measurements were analyzed in terms of a chemical equilibrium model that accounts for the multiplicity of ionic states of the reactants and products. These calculations led to values of thermodynamic quantities at T=298.15 K and I m =0 for a chemical reference reaction that involves specific ionic forms. Thus, for the reaction {2 glutathione red - (aq) + NADP ox 3- (aq)=glutathione ox 2- (aq) + NADP red 4- (aq) + H + (aq)}, the equilibrium constant K=(6.5±4.4)·10 -11 , the standard molar enthalpy of reaction Δ r H o m =(6.9±3.0) kJ · mol -1 , the standard molar Gibbs free energy change Δ r G o m =(58.1±1.7) kJ · mol -1 , and the standard molar entropy change Δ r S o m =-(172±12) J · K -1 · mol -1 . Under approximately physiological conditions (T=311.15 K, pH=7.0, and I m =0.25 mol · kg -1 the apparent equilibrium constant K ' ∼0.013. The results of the several studies of this reaction from the literature have also been examined and analyzed using the chemical equilibrium model. It was found that much of the literature is in agreement with the results of this study. Use of our results together with a value from the literature for the standard electromotive force E o for the NADP redox reaction leads to E o =0.166 V (T=298.15 K and I

The level of menadione redox-cycling in pancreatic β-cells is proportional to the glucose concentration: role of NADH and consequences for insulin secretion.

Science.gov (United States)

Heart, Emma; Palo, Meridith; Womack, Trayce; Smith, Peter J S; Gray, Joshua P

2012-01-15

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4-7mM) to stimulatory (8-16mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H(2)O(2)), a newly recognized coupling factor linking glucose metabolism to insulin secretion. However, high and toxic levels of H(2)O(2) inhibit insulin secretion. Menadione, which produces H(2)O(2) via redox cycling mechanism in a dose-dependent manner, was investigated for its effect on β-cell metabolism and insulin secretion in INS-1 832/13, a rat β-cell insulinoma cell line, and primary rodent islets. Menadione-dependent redox cycling and resulting H(2)O(2) production under stimulatory glucose exceeded several-fold those reached at basal glucose. This was paralleled by a differential effect of menadione (0.1-10μM) on insulin secretion, which was enhanced at basal, but inhibited at stimulatory glucose. Redox cycling of menadione and H(2)O(2) formation was dependent on glycolytically-derived NADH, as inhibition of glycolysis and application of non-glycogenic insulin secretagogues did not support redox cycling. In addition, activity of plasma membrane electron transport, a system dependent in part on glycolytically-derived NADH, was also inhibited by menadione. Menadione-dependent redox cycling was sensitive to the NQO1 inhibitor dicoumarol and the flavoprotein inhibitor diphenylene iodonium, suggesting a role for NQO1 and other oxidoreductases in this process. These data may explain the apparent dichotomy between the stimulatory and inhibitory effects of H(2)O(2) and menadione on insulin secretion. Published by Elsevier Inc.

Interactive effects of herbicide and enhanced UV-B on growth, oxidative damage and the ascorbate-glutathione cycle in two Azolla species.

Science.gov (United States)

Prasad, Sheo Mohan; Kumar, Sushil; Parihar, Parul; Singh, Rachana

2016-11-01

A field experiment was conducted to investigate the impact of alone and combined exposures of herbicide pretilachlor (5, 10 and 20μgml(-1)) and enhanced UV-B radiation (UV-B1; ambient +2.2kJm(-2) day(-1) and UV-B2; ambient +4.4kJm(-2) day(-1)) on growth, oxidative stress and the ascorbate-glutathione (AsA-GSH) cycle in two agronomically important Azolla spp. viz., Azolla microphylla and Azolla pinnata. Decreased relative growth rate (RGR) in both the species under tested stress could be linked to enhanced oxidative stress, thus higher H2O2 accumulation was observed, that in turn might have caused severe damage to lipids and proteins, thereby decreasing membrane stability. The effects were exacerbated when spp. were exposed to combined treatments of enhanced UV-B and pretilachlor. Detoxification of H2O2 is regulated by enzymes/metabolites of AsA-GSH cycle such as ascorbate peroxidase (APX) and glutathione reductase (GR) activity that were found to be stimulated. While, dehydroascorabte reductase (DHAR) activity, and the amount of metabolites: ascorbate (AsA), glutathione (GSH) and ratios of reduced/oxidized AsA (AsA/DHA) and GSH (GSH/GSSG), showed significant reduction with increasing doses of both the stressors, either applied alone or in combination. Glutathione-S-transferase (GST), an enzyme involved in scavenging of xenobiotics, was found to be stimulated under the tested stress. This study suggests that decline in DHAR activity and in AsA/DHA ratio might have led to enhanced H2O2 accumulation, thus decreased RGR was noticed under tested stress in both the species and the effect was more pronounced in A. pinnata. Owing to better performance of AsA-GSH cycle in A. microphylla, this study substantiates the view that A. microphylla is more tolerant than A. pinnata. Copyright © 2016 Elsevier Inc. All rights reserved.

CHANGES IN THE GLUTATHIONE SYSTEM IN P19 EMBRYONAL CARCINOMA CELLS UNDER HYPOXIC CONDITIONS

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D. S. Orlov

2015-01-01

Full Text Available Introduction. According to modern perceptions, tumor growth, along with oxidative stress formation, is accompanied by hypoxia. Nowadays studying the regulation of cellular molecular system functioning by conformational changes in proteins appears to be a topical issue. Research goal was to evaluate the state of the glutathione system and the level of protein glutathionylation in P19 embryonal carcinoma (EC cells under hypoxic conditions.Material and methods. P19 EC cells (mouse embryonal carcinoma cultured under normoxic and hypox-ic conditions served the research material.The concentration of total, oxidized, reduced and protein-bound glutathione, the reduced to oxidized thiol ratio as well as glutathione peroxidase and glutathione reductase activity were determined by spectropho-tometry.Results. Glutathione imbalance was accompanied by a decrease in P19 EC cell redox status under hypox-ic conditions against the backdrop of a rise in protein-bound glutathione.Conclusions. As a result of the conducted study oxidative stress formation was identified when modeling hypoxia in P19 embryonal carcinoma cells. The rise in the concentration of protein-bound glutathione may indicate the role of protein glutathionylation in regulation of P19 cell metabolism and functions un-der hypoxia. 

Can Mn–S redox cycling drive sedimentary dolomite formation? A hypothesis

Energy Technology Data Exchange (ETDEWEB)

Petrash, Daniel A.; Lalonde, Stefan V.; González-Arismendi, Gabriela; Gordon, Robert A.; Méndez, José A.; Gingras, Murray K.; Konhauser, Kurt O. (CLS); (UCV-Venezuela); (CNRS-UMR); (Alberta)

2016-06-10

The formation of dolomite in modern peritidal environments is linked to the degradation of buried microbial mats, with complexation of Ca and Mg by extracellular polymeric substances (EPSs) and alkalinity generation through organic carbon respiration facilitating the nucleation of dolomite precursors. In the past two decades, microbial sulfate reduction, methanogenesis, and methanotrophy have all been considered as potential drivers of the nucleation process, but it remains unclear why dolomite formation could not also occur in suboxic sediments where abundant alkalinity is produced by processes linked to Mn(IV) and/or Fe(III) reduction coupled with the diffusion and reoxidation of reduced sulfur species. Here we report the interstitial occurrence of spheroidal aggregates of nanometer-scale Ca-rich dolomite rhombohedra within suboxic sediments associated with remnant microbial mats that developed in the peritidal zone of the Archipelago Los Roques, Venezuela. Multiple analytical tools, including EPMA, ICP-MS, synchrotron-based XRF and XRD, and spatially resolved XANES microanalyses, show that the dolomite-cemented interval exhibits depleted bulk iron concentrations, but is interstitially enriched in Mn and elemental sulfur (S⁰). Manganese occurs in several oxidation states, indicating that the dolomite-cemented interval was the locus of complex biological redox transformations characterized by coupled Mn and S cycling. The tight correspondence between sedimentary Mn and MgCO₃ concentrations further hints at a direct role for Mn during dolomitization. While additional studies are required to confirm its relevance in natural settings, we propose a model by which coupled Mn–S redox cycling may promote alkalinity generation and thus dolomite formation in manner similar to, or even more efficiently, than bacterial sulfate reduction alone.

Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

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Haider Raza

2013-05-01

Full Text Available Background/Aims: The components of cigarette smoke (CS have been implicated in the development of cancer as well as in cardiopulmonary diseases. We have previously reported increased oxidative stress in rat tissues induced by tobacco-specific toxins nicotine and 4-(N-methyl-N-nitrosamino-1-(3-pyridyl-1-butanone (NNK. Recently, we have also shown increased oxidative stress and associated inflammatory responses in various tissues after exposure to cigarette smoke. Methods: In this study, we have further investigated the effects of nose-only cigarette smoke exposure on mitochondrial functions and glutathione-dependent redox metabolism in tissues of BALB/C mice. Liver, kidney, heart and lung tissues were analyzed for oxidative stress, glutathione (GSH and cytochrome P450 dependent enzyme activities and mitochondrial functions after exposure to smoke generated by 9 cigarettes/day for 4 days. Control mice were exposed to air only. Results: An increase in oxidative stress as observed by increased production of reactive oxygen species (ROS and altered GSH metabolism was apparent in all the tissues, but lung and heart appeared to be the main targets. Increased expression and activity of CYP450 1A1 and 1A2 were also observed in the tissues after exposure to cigarette smoke. Mitochondrial respiratory dysfunction in the tissues, as observed by alterations in the activities of Complex I and IV enzymes, was also observed after exposure to cigarette smoke. SDS-PAGE and Western blot results also indicate that alterations in the expression of enzyme proteins were in accordance with the changes in their catalytic functions. Conclusion: These results suggest that even short term exposure of cigarette smoke have adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking.

Quantitative imaging of glutathione in live cells using a reversible reaction-based ratiometric fluorescent probe

Science.gov (United States)

Glutathione (GSH) plays an important role in maintaining redox homeostasis inside cells. Currently, there are no methods available to quantitatively assess the GSH concentration in live cells. Live cell fluorescence imaging revolutionized the understanding of cell biology and has become an indispens...

Redox signaling in acute pancreatitis

Science.gov (United States)

Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

2015-01-01

Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

Redox signaling in acute pancreatitis

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Salvador Pérez

2015-08-01

Full Text Available Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

Beyond the Fe-P-redox connection: preferential regeneration of phosphorus from organic matter as a key control on Baltic Sea nutriënt cycles

NARCIS (Netherlands)

Jilbert, T.; Slomp, C.P.; Gustafsson, B.G.; Boer, W.

2011-01-01

Patterns of regeneration and burial of phosphorus (P) in the Baltic Sea are strongly dependent on redox conditions. Redox varies spatially along water depth gradients and temporally in response to the seasonal cycle and multidecadal hydrographic variability. Alongside the well-documented link

Glycine Increases Insulin Sensitivity and Glutathione Biosynthesis and Protects against Oxidative Stress in a Model of Sucrose-Induced Insulin Resistance

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Mohammed El-Hafidi

2018-01-01

Full Text Available Oxidative stress and redox status play a central role in the link between insulin resistance (IR and lipotoxicity in metabolic syndrome. This mechanistic link may involve alterations in the glutathione redox state. We examined the effect of glycine supplementation to diet on glutathione biosynthesis, oxidative stress, IR, and insulin cell signaling in liver from sucrose-fed (SF rats characterized by IR and oxidative stress. Our hypothesis is that the correction of glutathione levels by glycine treatment leads to reduced oxidative stress, a mechanism associated with improved insulin signaling and IR. Glycine treatment decreases the levels of oxidative stress markers in liver from SF rats and increases the concentrations of glutathione (GSH and γ-glutamylcysteine and the amount of γ-glutamylcysteine synthetase (γ-GCS, a key enzyme of GSH biosynthesis in liver from SF rats. In liver from SF rats, glycine also decreases the insulin-induced phosphorylation of insulin receptor substrate-1 (ISR-1 in serine residue and increases the phosphorylation of insulin receptor β-subunit (IR-β in tyrosine residue. Thus, supplementing diets with glycine to correct GSH deficiency and to reduce oxidative stress provides significant metabolic benefits to SF rats by improving insulin sensitivity.

Mechanisms of the noxious inflammatory cycle in cystic fibrosis

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Freyssinet Jean-Marie

2009-03-01

Full Text Available Abstract Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508, accounting for this pathology, is retained in the endoplasmic reticulum (ER, induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis.

Anticancer Activity of Metal Complexes: Involvement of Redox Processes

Science.gov (United States)

Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

2012-01-01

Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells.

Science.gov (United States)

Duranti, Guglielmo; Ceci, Roberta; Sgrò, Paolo; Sabatini, Stefania; Di Luigi, Luigi

2017-05-01

Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.

Efficiency of two-step solar thermochemical non-stoichiometric redox cycles with heat recovery

International Nuclear Information System (INIS)

Lapp, J.; Davidson, J.H.; Lipiński, W.

2012-01-01

Improvements in the effectiveness of solid phase heat recovery and in the thermodynamic properties of metal oxides are the most important paths to achieving unprecedented thermal efficiencies of 10% and higher in non-stoichiometric solar redox reactors. In this paper, the impact of solid and gas phase heat recovery on the efficiency of a non-stoichiometric cerium dioxide-based H 2 O/CO 2 splitting cycle realized in a solar-driven reactor are evaluated in a parametric thermodynamic analysis. Application of solid phase heat recovery to the cycling metal oxide allows for lower reduction zone operating temperatures, simplifying reactor design. An optimum temperature for metal oxide reduction results from two competing phenomena as the reduction temperature is increased: increasing re-radiation losses from the reactor aperture and decreasing heat loss due to imperfect solid phase heat recovery. Additionally, solid phase heat recovery increases the efficiency gains made possible by gas phase heat recovery. -- Highlights: ► Both solid and gas phase heat recovery are essential to achieve high thermal efficiency in non-stoichiometric ceria-based solar redox reactors. ► Solid phase heat recovery allows for lower reduction temperatures and increases the gains made possible by gas phase heat recovery. ► The optimum reduction temperature increases with increasing concentration ratio and decreasing solid phase heat recovery effectiveness. ► Even moderate levels of heat recovery dramatically improve reactor efficiency from 3.5% to 16%.

THE THIOREDOXIN SYSTEM IN REGULATING MCF-7 CELL PROLIFERATION UNDER REDOX STATUS MODULATION

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E. A. Stepovaya

2016-01-01

Full Text Available Introduction. Despite the available data on tumor cell functioning under the conditions of free radical-mediated oxidation, the mechanisms of redox regulation, cell proliferation management and apoptosis avoidance remain understudied.The objective of the study was to identify the role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation under redox status modulation with 1.4-dithioerythritol.Material and methods. The studies were conducted on the MCF-7 breast cancer cell line, grown in adherent cell culture. Cell redox status was modulated with5 mM N-ethylmaleimide – an SH group and peptide inhibitor and5 mM 1.4-dithioerythritol – a thiol group protector. The cell cycle was evaluated by flow cytometry, the same technique was used to measure the reactive oxygen species concentration. The levels of reduced and oxidized glutathione and the activity of thioredoxin reductase were identified by spectrophotometry. The intracellular concentrations of thioredoxin, cyclin E and cyclin-dependent kinase 2 were determined by Western blot analysis.Results and discussion. The essential role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation was exhibited. S-phase arrest under the effect of N-ethylmaleimide and G0/G1-phase arrest under the effect of 1.4-dithioerythritol are associated with the changes in the activity of redox-sensitive protein complexes (cyclins and cyclin-dependent kinases that regulate cell proliferation.Conclusion. Redoxdependent modulation of proliferation regulating intracellular protein activity occurs due to the thioredoxin system. This is a promising research area for seeking molecular targets of breast cell malignization. 

Oxidation of extracellular cysteine/cystine redox state in bleomycin-induced lung fibrosis.

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Iyer, Smita S; Ramirez, Allan M; Ritzenthaler, Jeffrey D; Torres-Gonzalez, Edilson; Roser-Page, Susanne; Mora, Ana L; Brigham, Kenneth L; Jones, Dean P; Roman, Jesse; Rojas, Mauricio

2009-01-01

Several lines of evidence indicate that depletion of glutathione (GSH), a critical thiol antioxidant, is associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, GSH synthesis depends on the amino acid cysteine (Cys), and relatively little is known about the regulation of Cys in fibrosis. Cys and its disulfide, cystine (CySS), constitute the most abundant low-molecular weight thiol/disulfide redox couple in the plasma, and the Cys/CySS redox state (E(h) Cys/CySS) is oxidized in association with age and smoking, known risk factors for IPF. Furthermore, oxidized E(h) Cys/CySS in the culture media of lung fibroblasts stimulates proliferation and expression of transitional matrix components. The present study was undertaken to determine whether bleomycin-induced lung fibrosis is associated with a decrease in Cys and/or an oxidation of the Cys/CySS redox state and to determine whether these changes were associated with changes in E(h) GSH/glutathione disulfide (GSSG). We observed distinct effects on plasma GSH and Cys redox systems during the progression of bleomycin-induced lung injury. Plasma E(h) GSH/GSSG was selectively oxidized during the proinflammatory phase, whereas oxidation of E(h) Cys/CySS occurred at the fibrotic phase. In the epithelial lining fluid, oxidation of E(h) Cys/CySS was due to decreased food intake. Thus the data show that decreased precursor availability and enhanced oxidation of Cys each contribute to the oxidation of extracellular Cys/CySS redox state in bleomycin-induced lung fibrosis.

Structural Basis for Redox Regulation of Cytoplasmic and Chloroplastic Triosephosphate Isomerases from Arabidopsis thaliana

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Laura Margarita López-Castillo

2016-12-01

Full Text Available In plants triosephosphate isomerase (TPI interconverts glyceraldehyde 3-phosphate (G3P and dihydroxyacetone phosphate (DHAP during glycolysis, gluconeogenesis, and the Calvin-Benson cycle. The nuclear genome of land plants encodes two tpi genes, one gene product is located in the cytoplasm and the other is imported into the chloroplast. Herein we report the crystal structures of the TPIs from the vascular plant Arabidopsis thaliana (AtTPIs and address their enzymatic modulation by redox agents. Cytoplasmic TPI (cTPI and chloroplast TPI (pdTPI share more than 60% amino acid identity and assemble as (β-α8 dimers with high structural homology. cTPI and pdTPI harbor two and one accessible thiol groups per monomer respectively. cTPI and pdTPI present a cysteine at an equivalent structural position (C13 and C15 respectively and cTPI also contains a specific solvent accessible cysteine at residue 218 (cTPI-C218. Site directed mutagenesis of residues pdTPI-C15, cTPI-C13 and cTPI-C218 to serine substantially decreases enzymatic activity, indicating that the structural integrity of these cysteines is necessary for catalysis. AtTPIs exhibit differential responses to oxidative agents, cTPI is susceptible to oxidative agents such as diamide and H2O2, whereas pdTPI is resistant to inhibition. Incubation of AtTPIs with the sulfhydryl conjugating reagents methylmethane thiosulfonate (MMTS and glutathione inhibits enzymatic activity. However, the concentration necessary to inhibit pdTPI is at least two orders of magnitude higher than the concentration needed to inhibit cTPI. Western-blot analysis indicates that residues cTPI-C13, cTPI-C218, and pdTPI-C15 conjugate with glutathione. In summary, our data indicate that AtTPIs could be redox regulated by the derivatization of specific AtTPI cysteines (cTPI-C13 and pdTPI-C15 and cTPI-C218. Since AtTPIs have evolved by gene duplication, the higher resistance of pdTPI to redox agents may be an adaptive consequence to

Roles of catalase and glutathione peroxidase in the tolerance of a pulmonate gastropod to anoxia and reoxygenation.

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Welker, Alexis F; Moreira, Daniel C; Hermes-Lima, Marcelo

2016-07-01

Humans and most mammals suffer severe damage when exposed to ischemia and reperfusion episodes due to an overproduction of reactive oxygen species (ROS). In contrast, several hypoxia/anoxia-tolerant animals survive very similar situations. We evaluated herein the redox metabolism in the anoxia-tolerant land snail Helix aspersa after catalase inhibition by 3-amino-1,2,4-triazole (ATZ) injection during a cycle of wide and abrupt change in oxygen availability. The exposure to anoxia for 5 h caused a change of only one of several parameters related to free radical metabolism: a rise in selenium-dependent glutathione peroxidase (Se-GPX) activity in muscle of both saline- and ATZ-injected animals (by 1.9- and 1.8-fold, respectively). Catalase suppression had no effect in animals under normoxia or anoxia. However, during reoxygenation catalase suppression kept high levels of muscle Se-GPX activity (twofold higher than in saline-injected snails up to 30 min reoxygenation) and induced the increase in hepatopancreas SOD activity (by 22 %), indicating higher levels of ROS in both organs than in saline-injected animals. Additionally, catalase-suppressed snails showed 12 % higher levels of carbonyl protein-a sign of mild oxidative stress-in muscle during reoxygenation than those animals with intact catalase. No changes were observed in glutathione parameters (GSH, GSSG and GSSG:GSH ratio), TBARS, and GST activity in any of the experimental groups, in both organs. These results indicate that catalase inhibition inflicts changes in the free radical metabolism during reoxygenation, prompting a stress-response that is a reorganization in other enzymatic antioxidant defenses to minimize alterations in the redox homeostasis in land snails.

Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.

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Zimmermann, Stefanie; Oufir, Mouhssin; Leroux, Alejandro; Krauth-Siegel, R Luise; Becker, Katja; Kaiser, Marcel; Brun, Reto; Hamburger, Matthias; Adams, Michael

2013-11-15

In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma brucei-the causative agent of Human African Trypanosomiasis-by a so far unknown mechanism. We hypothesized that CYNs α,β-unsaturated methylene moieties act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)2), the main low molecular mass thiols essential for unique redox metabolism of these parasites. The analysis of this putative mechanism and the effects of CYN on enzymes of the T(SH)2 redox metabolism including trypanothione reductase, trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase are shown. A two step extraction protocol with subsequent UPLC-MS/MS analysis was established to quantify intra-cellular CYN, T(SH)2, GSH, as well as GS-CYN and T(S-CYN)2 adducts in intact T. b. rhodesiense cells. Within minutes of exposure to CYN, the cellular GSH and T(SH)2 pools were entirely depleted, and the parasites entered an apoptotic stage and died. CYN also showed inhibition of the ornithine decarboxylase similar to the positive control eflornithine. Significant interactions with the other enzymes involved in the T(SH)2 redox metabolism were not observed. Alongside many other biological activities sesquiterpene lactones including CYN have shown antitrypanosomal effects, which have been postulated to be linked to formation of Michael adducts with cellular nucleophiles. Here the interaction of CYN with biological thiols in a cellular system in general, and with trypanosomal T(SH)2 redox metabolism in particular, thus offering a molecular explanation for the antitrypanosomal activity is demonstrated. At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Species-Specific Thiol-Disulfide Equilibrium Constant: A Tool To Characterize Redox Transitions of Biological Importance.

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Mirzahosseini, Arash; Somlyay, Máté; Noszál, Béla

2015-08-13

Microscopic redox equilibrium constants, a new species-specific type of physicochemical parameters, were introduced and determined to quantify thiol-disulfide equilibria of biological significance. The thiol-disulfide redox equilibria of glutathione with cysteamine, cysteine, and homocysteine were approached from both sides, and the equilibrium mixtures were analyzed by quantitative NMR methods to characterize the highly composite, co-dependent acid-base and redox equilibria. The directly obtained, pH-dependent, conditional constants were then decomposed by a new evaluation method, resulting in pH-independent, microscopic redox equilibrium constants for the first time. The 80 different, microscopic redox equilibrium constant values show close correlation with the respective thiolate basicities and provide sound means for the development of potent agents against oxidative stress.

Asada-Halliwell pathway maintains redox status in Dioscorea alata tuber which helps in germination.

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Sharma, Shruti; Sehrawat, Ankita; Deswal, Renu

2016-09-01

Reactive Oxygen Species (ROS) are important regulatory molecules governing physiological processes. In the present study a biochemical and proteome level comparison of two contrasting growth stages of Dioscorea alata tuber namely germinating and mature tuber was performed in order to understand the tuber physiology and biochemistry. Existence of all the component enzymes [APx (ascorbate peroxidase), GR (glutathione reductase), DHAR (dehydroascorbate reductase), MDHAR (mono-dehydroascorbate reductase)] and major products [ascorbate (ASC) and glutathione (GSH)] of the cycle showed an operational Asada-Halliwell cycle in the tuber. A 2.65 fold increase in ASC content & a 3.8 fold increase in GR activity fortified the redox milieu during germination. In contrast a 5 fold higher H2O2 content (due to 3.08 fold lower APx activity) and accumulation of reactive nitrogen species (RNS) such as nitric oxide (NO, 2.4-fold) and S-nitrosothiol (SNO, 2.08 fold) contributed to overall oxidative conditions in the mature tuber. The carbonic anhydrase (CA, 7.5 fold), DHAR (5.31 fold) and MDHAR (7 fold) activities were higher in the germinating tuber in comparison with the mature tuber. GSNO negatively regulated the CA (3.6 & 3.95 fold), MDHAR (7.5 & 1.5 fold) and APx (2.3 & 1.81 fold) while another NO donor, CysNO negatively regulated the DHAR (2.24 & 1.32 fold) activity in the mature and germinating stages respectively indicating again that the lesser inhibition by NO (via nitrosylation) may be because of overall reducing environment in the germinating tuber. Increased SNO leading to S-nitrosylation of dioscorin was confirmed by Biotin switch assay. This is the first report showing dioscorin nitrosylation. The present analysis showed differential redox regulation and also suggests the physiological relevance of CA, DHAR, MDHAR, APx & GR in tuber germination for the first time. These enzymes may be used as potential markers of tuber germination in future. Copyright © 2016 Elsevier

Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency

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Anna-Kaisa Niemi

2014-01-01

Full Text Available The pathophysiology of succinic semialdehyde dehydrogenase (SSADH deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH, and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients.

Nrf2 and Redox Status in Prediabetic and Diabetic Patients

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Angélica S. Jiménez-Osorio

2014-11-01

Full Text Available The redox status associated with nuclear factor erythroid 2-related factor-2 (Nrf2 was evaluated in prediabetic and diabetic subjects. Total antioxidant status (TAS in plasma and erythrocytes, glutathione (GSH and malondialdehyde (MDA content and activity of antioxidant enzymes were measured as redox status markers in 259 controls, 111 prediabetics and 186 diabetic type 2 subjects. Nrf2 was measured in nuclear extract fractions from peripheral blood mononuclear cells (PBMC. Nrf2 levels were lower in prediabetic and diabetic patients. TAS, GSH and activity of glutamate cysteine ligase were lower in diabetic subjects. An increase of MDA and superoxide dismutase activity was found in diabetic subjects. These results suggest that low levels of Nrf2 are involved in the development of oxidative stress and redox status disbalance in diabetic patients.

Phenolic acids potentiate colistin-mediated killing of Acinetobacter baumannii by inducing redox imbalance.

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Ajiboye, Taofeek O; Skiebe, Evelyn; Wilharm, Gottfried

2018-05-01

Phenolic acids with catechol groups are good prooxidants because of their low redox potential. In this study, we provided data showing that phenolic acids, caffeic acid, gallic acid and protocatechuic acid, enhanced colistin-mediated bacterial death by inducing redox imbalance. The minimum inhibitory concentrations of these phenolic acids against Acinetobacter baumannii AB5075 were considerably lowered for ΔsodB and ΔkatG mutants. Checkerboard assay shows synergistic interactions between colistin and phenolic acids. The phenolic acids exacerbated colistin-induced oxidative stress in A. baumannii AB5075 through increased superoxide anion generation, NAD + /NADH and ADP/ATP ratio. In parallel, the level of reduced glutathione was significantly lowered. We conclude that phenolic acids potentiate colistin-induced oxidative stress in A. baumannii AB5075 by increasing ROS generation, energy metabolism and electron transport chain activity with a concomitant decrease in glutathione. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Trapidil improves hemodynamic, echocardiographic and redox state parameters of right ventricle in monocrotaline-induced pulmonary arterial hypertension model.

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Türck, Patrick; Lacerda, Denise Santos; Carraro, Cristina Campos; de Lima-Seolin, Bruna Gazzi; Teixeira, Rayane Brinck; Poletto Bonetto, Jéssica Hellen; Colombo, Rafael; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

2018-04-10

Pulmonary arterial hypertension is a disease characterized by increased pulmonary vascular resistance and redox imbalance, leading to failure of right ventricle. Trapidil has been described to improve the redox balance and cardiac conditions. Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH. Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil. PAH was induced by an intraperitoneal injection of monocrotaline 60 mg/kg at day 0. Treatment started at day 7 (5 or 8 mg/kg/day) until day 14, when animals were euthanized after echocardiography and catheterism. Right ventricular systolic pressure and pressure/time derivatives were increased in monocrotaline animals. The increased right ventricular diameters in monocrotaline groups were reduced with trapidil. Monocrotaline groups showed higher lipid peroxidation and glutathione peroxidase activity. Trapidil reduced NADPH oxidases activities and increased the reduced glutathiones/total glutathiones ratio. Protein expression of phospholamban in RV was diminished in monocrotaline groups, whereas expression of RyR and SERCA was enhanced in the groups treated with trapidil. Our data suggest that trapidil induces an improvement in RV remodeling in PAH model, mitigating the progression of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

ENDURANCE TRAINING AND GLUTATHIONE-DEPENDENT ANTIOXIDANT DEFENSE MECHANISM IN HEART OF THE DIABETIC RATS

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Mustafa Atalay

2003-06-01

Full Text Available Regular physical exercise beneficially influences cardiac antioxidant defenses in normal rats. The aim of this study was to test whether endurance training can strengthen glutathione-dependent antioxidant defense mechanism and decrease lipid peroxidation in heart of the streptozotocin-induced diabetic rats. Redox status of glutathione in blood of diabetic rats in response to training and acute exercise was also examined. Eight weeks of treadmill training increased the endurance in streptozotocin-induced diabetic rats. It did not affect glutathione level in heart tissue at rest and also after exercise. On the other hand, endurance training decreased glutathione peroxidase activity in heart, while glutathione reductase and glutathione S-transferase activities were not affected either by acute exhaustive exercise or endurance training. Reduced and oxidized glutathione levels in blood were not affected by either training or acute exercise. Conjugated dienes levels in heart tissue were increased by acute exhaustive exercise and also 8 weeks treadmill training. Longer duration of exhaustion in trained group may have contributed to the increased conjugated dienes levels in heart after acute exercise. Our results suggest that endurance type exercise may make heart more susceptible to oxidative stress. Therefore it may be wise to combine aerobic exercise with insulin treatment to prevent its adverse effects on antioxidant defense in heart in patients with diabetes mellitus

The extracellular redox state modulates mitochondrial function, gluconeogenesis, and glycogen synthesis in murine hepatocytes.

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Nocito, Laura; Kleckner, Amber S; Yoo, Elsia J; Jones Iv, Albert R; Liesa, Marc; Corkey, Barbara E

2015-01-01

Circulating redox state changes, determined by the ratio of reduced/oxidized pairs of different metabolites, have been associated with metabolic diseases. However, the pathogenic contribution of these changes and whether they modulate normal tissue function is unclear. As alterations in hepatic gluconeogenesis and glycogen metabolism are hallmarks that characterize insulin resistance and type 2 diabetes, we tested whether imposed changes in the extracellular redox state could modulate these processes. Thus, primary hepatocytes were treated with different ratios of the following physiological extracellular redox couples: β-hydroxybutyrate (βOHB)/acetoacetate (Acoc), reduced glutathione (GSH)/oxidized glutathione (GSSG), and cysteine/cystine. Exposure to a more oxidized ratio via extracellular βOHB/Acoc, GSH/GSSG, and cysteine/cystine in hepatocytes from fed mice increased intracellular hydrogen peroxide without causing oxidative damage. On the other hand, addition of more reduced ratios of extracellular βOHB/Acoc led to increased NAD(P)H and maximal mitochondrial respiratory capacity in hepatocytes. Greater βOHB/Acoc ratios were also associated with decreased β-oxidation, as expected with enhanced lipogenesis. In hepatocytes from fasted mice, a more extracellular reduced state of βOHB/Acoc led to increased alanine-stimulated gluconeogenesis and enhanced glycogen synthesis capacity from added glucose. Thus, we demonstrated for the first time that the extracellular redox state regulates the major metabolic functions of the liver and involves changes in intracellular NADH, hydrogen peroxide, and mitochondrial respiration. Because redox state in the blood can be communicated to all metabolically sensitive tissues, this work confirms the hypothesis that circulating redox state may be an important regulator of whole body metabolism and contribute to alterations associated with metabolic diseases.

The extracellular redox state modulates mitochondrial function, gluconeogenesis, and glycogen synthesis in murine hepatocytes.

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Laura Nocito

Full Text Available Circulating redox state changes, determined by the ratio of reduced/oxidized pairs of different metabolites, have been associated with metabolic diseases. However, the pathogenic contribution of these changes and whether they modulate normal tissue function is unclear. As alterations in hepatic gluconeogenesis and glycogen metabolism are hallmarks that characterize insulin resistance and type 2 diabetes, we tested whether imposed changes in the extracellular redox state could modulate these processes. Thus, primary hepatocytes were treated with different ratios of the following physiological extracellular redox couples: β-hydroxybutyrate (βOHB/acetoacetate (Acoc, reduced glutathione (GSH/oxidized glutathione (GSSG, and cysteine/cystine. Exposure to a more oxidized ratio via extracellular βOHB/Acoc, GSH/GSSG, and cysteine/cystine in hepatocytes from fed mice increased intracellular hydrogen peroxide without causing oxidative damage. On the other hand, addition of more reduced ratios of extracellular βOHB/Acoc led to increased NAD(PH and maximal mitochondrial respiratory capacity in hepatocytes. Greater βOHB/Acoc ratios were also associated with decreased β-oxidation, as expected with enhanced lipogenesis. In hepatocytes from fasted mice, a more extracellular reduced state of βOHB/Acoc led to increased alanine-stimulated gluconeogenesis and enhanced glycogen synthesis capacity from added glucose. Thus, we demonstrated for the first time that the extracellular redox state regulates the major metabolic functions of the liver and involves changes in intracellular NADH, hydrogen peroxide, and mitochondrial respiration. Because redox state in the blood can be communicated to all metabolically sensitive tissues, this work confirms the hypothesis that circulating redox state may be an important regulator of whole body metabolism and contribute to alterations associated with metabolic diseases.

Avocado oil induces long-term alleviation of oxidative damage in kidney mitochondria from type 2 diabetic rats by improving glutathione status.

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Ortiz-Avila, Omar; Figueroa-García, María Del Consuelo; García-Berumen, Claudia Isabel; Calderón-Cortés, Elizabeth; Mejía-Barajas, Jorge A; Rodriguez-Orozco, Alain R; Mejía-Zepeda, Ricardo; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

2017-04-01

Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

The effects of redox controls mediated by glutathione peroxidases on root architecture in Arabidopsis thaliana.

Science.gov (United States)

Passaia, Gisele; Queval, Guillaume; Bai, Juan; Margis-Pinheiro, Marcia; Foyer, Christine H

2014-03-01

Glutathione peroxidases (GPXs) fulfil important functions in oxidative signalling and protect against the adverse effects of excessive oxidation. However, there has been no systematic characterization of the functions of the different GPX isoforms in plants. The roles of the different members of the Arabidopsis thaliana GPX gene (AtGPX) family were therefore investigated using gpx1, gpx2, gpx3, gpx4, gpx6, gpx7, and gpx8 T-DNA insertion mutant lines. The shoot phenotypes were largely similar in all genotypes, with small differences from the wild type observed only in the gpx2, gpx3, gpx7, and gpx8 mutants. In contrast, all the mutants showed altered root phenotypes compared with the wild type. The gpx1, gpx4, gpx6, gpx7, and gpx8 mutants had a significantly greater lateral root density (LRD) than the wild type. Conversely, the gpx2 and gpx3 mutants had significantly lower LRD values than the wild type. Auxin increased the LRD in all genotypes, but the effect of auxin was significantly greater in the gpx1, gpx4, and gpx7 mutants than in the wild type. The application of auxin increased GPX4 and GPX7 transcripts, but not GPX1 mRNAs in the roots of wild-type plants. The synthetic strigolactone GR24 and abscisic acid (ABA) decreased LRD to a similar extent in all genotypes, except gpx6, which showed increased sensitivity to ABA. These data not only demonstrate the importance of redox controls mediated by AtGPXs in the control of root architecture but they also show that the plastid-localized GPX1 and GPX7 isoforms are required for the hormone-mediated control of lateral root development.

In situ observations of microstructural changes in SOFC anodes during redox cycling

DEFF Research Database (Denmark)

Klemensø, Trine; Appel, C. C.; Mogensen, Mogens Bjerg

2006-01-01

The anode-supported solid oxide fuel cell (SOFC) degrades when the anode is subjected to redox cycling. The degradation has qualitatively been related to microstructural changes in the nickel-yttria stabilized zirconia anode of the tested cells. In this work, the microstructural changes were...... observed in situ using environmental scanning electron microscopy. In the reduced state, a dynamic rounding of the nickel particles occurred. The oxide growth upon re-oxidation depended on the oxidation kinetics. During rapid oxidation, the NiO particles divided into 2-4 particles, which grew...... into the surrounding voids. For slower oxidation, an external oxide layer was seen to develop around the individual particles. (c) 2006 The Electrochemical Society....

Redox Dysregulation in the Pathophysiology of Schizophrenia and Bipolar Disorder

DEFF Research Database (Denmark)

Kulak, Anita; Steullet, Pascal; Cabungcal, Jan-Harry

2013-01-01

Abstract Significance: Schizophrenia (SZ) and bipolar disorder (BD) are classified as two distinct diseases. However, accumulating evidence shows that both disorders share genetic, pathological, and epidemiological characteristics. Based on genetic and functional findings, redox dysregulation due...... abnormal prefrontal levels of glutathione (GSH), the major cellular redox regulator and antioxidant. Here we review experimental data from rodent models demonstrating that permanent as well as transient GSH deficit results in behavioral, morphological, electrophysiological, and neurochemical alterations...... hypofunction, elevated glutamate levels, impairment of parvalbumin GABA interneurons, abnormal neuronal synchronization, altered dopamine neurotransmission, and deficient myelination. Critical Issues: Treatment with the GSH precursor and antioxidant N-acetylcysteine normalizes some of those deficits in mice...

The reactivity of Fe(II) associated with goethite formed during short redox cycles toward Cr(VI) reduction under oxic conditions

Energy Technology Data Exchange (ETDEWEB)

Tomaszewski, Elizabeth J.; Lee, Seungyeol; Rudolph, Jared; Xu, Huifang; Ginder-Vogel, Matthew (UW)

2017-08-01

Chromium (Cr) is a toxic metal that causes a myriad of health problems and enters the environment as a result of anthropogenic activities and/or natural processes. The toxicity and solubility of chromium is linked to its oxidation state; Cr(III) is poorly soluble and relatively nontoxic, while Cr(VI) is soluble and a known carcinogen. Solid Fe(II) in iron-bearing minerals, such as pyrite, magnetite, and green rusts, reduce the oxidation state of chromium, reducing its toxicity and mobility. However, these minerals are not the only potential sources of solid-associated Fe(II) available for Cr(VI) reduction. For example, ferric (Fe(III)) (hydr)oxides, such as goethite or hematite, can have Fe(II) in the solid without phase transformation; however, the reactivity of Fe(II) within Fe(III) (hydr)oxides with contaminants, has not been previously investigated. Here, we cyclically react goethite with dissolved Fe(II) followed by dissolved O2, leading to the formation of reactive Fe(II) associated with goethite. In separate reactors, the reactivity of this Fe(II) is probed under oxic conditions, by exposure to chromate (CrO42 -) after either one, two, three or four redox cycles. Cr is not present during redox cycling; rather, it is introduced to a subset of the solid after each oxidation half-cycle. Analysis of X-ray absorption near edge structure (XANES) spectra reveals that the extent of Cr(VI) reduction to Cr(III) depends not only on solid Fe(II) content but also surface area and mean size of ordered crystalline domains, determined by BET surface area analysis and X-ray diffraction (XRD), respectively. Shell-by-shell fitting of the extended X-ray absorption fine structure (EXAFS) spectra demonstrates chromium forms both single and double corner sharing complexes on the surface of goethite, in addition to sorbed Cr(III) species. Finally, transmission electron microscope (TEM) imaging and X-ray energy-dispersive spectroscopy (EDS) illustrate that Cr preferentially

Redox cycling-based amplifying electrochemical sensor for in situ clozapine antipsychotic treatment monitoring

International Nuclear Information System (INIS)

Ben-Yoav, Hadar; Winkler, Thomas E.; Kim, Eunkyoung; Chocron, Sheryl E.; Kelly, Deanna L.; Payne, Gregory F.; Ghodssi, Reza

2014-01-01

Highlights: • A new concept for clozapine in situ sensing with minimal pre-treatment procedures. • A catechol-chitosan redox cycling system amplifies clozapine oxidation current. • The modified amplifier signal is 3 times greater than the unmodified system. • Differentiation between clozapine and its metabolite norclozapine has been shown. • The sensor has the capability to detect clozapine in human serum. - Abstract: Schizophrenia is a lifelong mental disorder with few recent advances in treatment. Clozapine is the most effective antipsychotic for schizophrenia treatment. However, it remains underutilized since frequent blood draws are required to monitor adverse side effects, and maintain clozapine concentrations in a therapeutic range. Micro-system technology utilized towards real-time monitoring of efficacy and safety will enable personalized medicine and better use of this medication. Although work has been reported on clozapine detection using its electrochemical oxidation, no in situ monitoring of clozapine has been described. In this work, we present a new concept for clozapine in situ sensing based on amplifying its oxidation current. Specifically, we use a biofabricated catechol-modified chitosan redox cycling system to provide a significant amplification of the generated oxidizing current of clozapine through a continuous cycle of clozapine reduction followed by re-oxidation. The amplified signal has improved the signal-to-noise ratio and provided the required limit-of-detection and dynamic range for clinical applications with minimal pre-treatment procedures. The sensor reports on the functionality and sensitivity of clozapine detection between 0.1 and 10 μg/mL. The signal generated by clozapine using the catechol-modified chitosan amplifier has shown to be 3 times greater than the unmodified system. The sensor has the ability to differentiate between clozapine and its metabolite norclozapine, as well as the feasibility to detect clozapine in

Impact of the redox-cycling herbicide diquat on transcript expression and antioxidant enzymatic activities of the freshwater snail Lymnaea stagnalis

Energy Technology Data Exchange (ETDEWEB)

Bouetard, Anthony, E-mail: anthony.bouetard@rennes.inra.fr [INRA, UMR INRA-Agrocampus Ouest ESE 0985, Equipe Ecotoxicologie et Qualite des Milieux Aquatiques, 65 rue de Saint-Brieuc, 35042 Rennes cedex (France); Besnard, Anne-Laure; Vassaux, Daniele; Lagadic, Laurent; Coutellec, Marie-Agnes [INRA, UMR INRA-Agrocampus Ouest ESE 0985, Equipe Ecotoxicologie et Qualite des Milieux Aquatiques, 65 rue de Saint-Brieuc, 35042 Rennes cedex (France)

2013-01-15

The presence of pesticides in the environment results in potential unwanted effects on non-target species. Freshwater organisms inhabiting water bodies adjacent to agricultural areas, such as ditches, ponds and marshes, are good models to test such effects as various pesticides may reach these habitats through several ways, including aerial drift, run-off, and drainage. Diquat is a non-selective herbicide used for crop protection or for weed control in such water bodies. In this study, we investigated the effects of diquat on a widely spread aquatic invertebrate, the holarctic freshwater snail Lymnaea stagnalis. Due to the known redox-cycling properties of diquat, we studied transcript expression and enzymatic activities relative to oxidative and general stress in the haemolymph and gonado-digestive complex (GDC). As diquat is not persistent, snails were exposed for short times (5, 24, and 48 h) to ecologically relevant concentrations (22.2, 44.4, and 222.2 {mu}g l{sup -1}) of diquat dibromide. RT-qPCR was used to quantify the transcription of genes encoding catalase (cat), a cytosolic superoxide dismutase (Cu/Zn-sod), a selenium-dependent glutathione peroxidase (gpx), a glutathione reductase (gred), the retinoid X receptor (rxr), two heat shock proteins (hsp40 and hsp70), cortactin (cor) and the two ribosomal genes r18S and r28s. Enzymatic activities of SOD, Gpx, Gred and glutathione S-transferase (GST) were investigated in the GDC using spectrophoto/fluorometric methods. Opposite trends were obtained in the haemolymph depending on the herbicide concentration. At the lowest concentration, effects were mainly observed after 24 h of exposure, with over-transcription of cor, hsp40, rxr, and sod, whereas higher concentrations down-regulated the expression of most of the studied transcripts, especially after 48 h of exposure. In the GDC, earlier responses were observed and the fold-change magnitude was generally much higher: transcription of all target genes increased

Expression of inducible nitric oxide synthase in endotoxemic rat hepatocytes is dependent on the cellular glutathione status

NARCIS (Netherlands)

Vos, TA; van Goor, H; Tuyt, L; de Jager-Krikken, A; Leuvenink, R; Kuipers, F; Jansen, PLM; Moshage, H

The inducible nitric oxide synthase (iNOS) promoter contains nuclear factor kappa B (NF-kappa B) binding sites. NF-kappa B activation is determined, in part, by the intracellular redox status, The aim of this study was to determine the importance of the cellular glutathione status in relation to

Capacitance enhancement of polyaniline coated curved-graphene supercapacitors in a redox-active electrolyte

Science.gov (United States)

Chen, Wei; Rakhi, R. B.; Alshareef, H. N.

2013-05-01

We show, for the first time, a redox-active electrolyte in combination with a polyaniline-coated curved graphene active material to achieve significant enhancement in the capacitance (36-92% increase) compared to supercapacitors that lack the redox-active contribution from the electrolyte. The supercapacitors based on the redox-active electrolyte also exhibit excellent rate capability and very long cycling performance (>50 000 cycles).We show, for the first time, a redox-active electrolyte in combination with a polyaniline-coated curved graphene active material to achieve significant enhancement in the capacitance (36-92% increase) compared to supercapacitors that lack the redox-active contribution from the electrolyte. The supercapacitors based on the redox-active electrolyte also exhibit excellent rate capability and very long cycling performance (>50 000 cycles). Electronic supplementary information (ESI) available: Experimental section, supporting figures including SEM, TEM, XPS, BET, CV and CD curves and a summary table of capacitance. See DOI: 10.1039/c3nr00773a

The effect of pre-exercise ingestion of corinthian currant on endurance performance and blood redox status.

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Deli, Chariklia K; Poulios, Athanasios; Georgakouli, Kalliopi; Papanikolaou, Konstantinos; Papoutsis, Alexandros; Selemekou, Maria; Karathanos, Vaios T; Draganidis, Dimitris; Tsiokanos, Athanasios; Koutedakis, Yiannis; Fatouros, Ioannis G; Jamurtas, Athanasios Z

2018-02-22

The present study investigated the effect of Corinthian currant pre-exercise supplementation on metabolism, performance and blood redox status during, and after prolonged exercise. Eleven healthy participants (21-45y) performed a 90-min constant-intensity (60-70% VO 2max ) submaximal-trial, plus a time-trial (TT) to exhaustion (95% VO 2max ) after consuming an isocaloric (1.5g CHO/kg BM) amount of randomly assigned Corinthian currant or glucose-drink, or water (control). Blood was drawn at baseline, pre-exercise, 30min, 60min, 90min of submaximal-trial, post-TT, and 1h post-TT. Post-ingestion blood glucose (GLU) under Corinthian currant was higher compared with water, and similar compared with glucose-drink throughout the study. Respiratory quotient under Corinthian currant was similar with glucose-drink and higher than water throughout the submaximal trial. Accordingly, higher CHO and lower fat oxidation were observed under Corinthian currant compared with water. The TT performance was similar between Corinthian currant, glucose-drink and water. Redox status were similar under all three conditions. Reduced glutathione (GSH) declined while total antioxidant capacity (TAC) and uric acid increased during exercise. GSH and TAC returned to baseline, while uric acid remained increased the following 1h. Corinthian currant, although did not alter exercise-mediated redox status changes and performance, was equally effective to a glucose-drink in maintaining GLU levels during prolonged cycling.

Improved stress tolerance and productivity in transgenic rice plants constitutively expressing the Oryza sativa glutathione synthetase OsGS under paddy field conditions.

Science.gov (United States)

Park, Seong-Im; Kim, Young-Saeng; Kim, Jin-Ju; Mok, Ji-Eun; Kim, Yul-Ho; Park, Hyang-Mi; Kim, Il-Sup; Yoon, Ho-Sung

2017-08-01

Reactive oxygen species, which increase under various environmental stresses, have deleterious effects on plants. An important antioxidant, glutathione, is used to detoxify reactive oxygen species in plant cells and is mainly produced by two enzymes: gamma-glutamylcysteine synthetase (γ-ECS) and glutathione synthetase (GS). To evaluate the functional roles of the glutathione synthetase gene (OsGS) in rice, we generated four independent transgenic rice plants (TG1-TG4) that overexpressed OsGS under the control of the constitutively expressed OsCc1 promoter. When grown under natural paddy field conditions, the TG rice plants exhibited greater growth development, higher chlorophyll content, and higher GSH/GSSH ratios than control wild-type (WT) rice plants. Subsequently, the TG rice plants enhanced redox homeostasis by preventing hydroperoxide-mediated membrane damage, which improved their adaptation to environmental stresses. As a result, TG rice plants improved rice grain yield and total biomass following increases in panicle number and number of spikelets per panicle, despite differences in climate during the cultivation periods of 2014 and 2015. Overall, our results indicate that OsGS overexpression improved redox homeostasis by enhancing the glutathione pool, which resulted in greater tolerance to environmental stresses in the paddy fields. Copyright © 2017. Published by Elsevier GmbH.

The effect of cycling on the nanoscale morphology and redox properties of poly[2,2′-bithiophene

International Nuclear Information System (INIS)

O’Neil, K.D.; Smith, A.; Forristal, T.A.; Semenikhin, O.A.

2013-01-01

The changes in the redox behavior and nanoscale morphology of poly[2,2′-bithiophene] deposited onto highly oriented pyrolytic graphite substrates upon repeated doping–undoping were studied. It was shown that repeated cycling resulted in very particular changes in the voltammetric response of the polymer films as well as their nanoscale morphology. Specifically, when the cycling was performed to relatively low anodic potentials, the overall doping–undoping charge did not change; however, the shape of voltammograms was consistently changing showing broadening of the voltammograms and reducing of the doping peak height in the anodic scan, as well as broadening and deterioration of the undoping peak in the reverse scan. Furthermore, a remarkable feature was observed that all voltammogram traces intersected at several characteristic potentials producing quasi-isosbestic points. With an increase in the anodic scan potential limit, the overall doping–undoping charge starts to decrease showing irreversible degradation of the polymer; however, the general pattern of the peak broadening could be still observed. Atomic force microscopic (AFM) studies of the polymer films cycled to various anodic limits showed that repeated cycling resulted in a gradual decrease in the degree of crystallinity, as revealed by AFM phase imaging, and an increase in the degree of disorder. Coupled with the changes in the redox behavior, these findings suggested the formation of more flexible and open polymer nanostructure that enables easier penetration of the dopant ions and solvent. However, at the same time, an increase in the degree of disorder reduced the interchain interactions and inhibited the formation of extended electronic states delocalized across neighboring polymer chains. This occurred at first without irreversible degradation of the polymer and a decrease in the overall doping–undoping charge. Cycling to higher anodic potentials resulted in irreversible degradation

Differential regulation of tissue thiol-disulfide redox status in a murine model of peritonitis

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Benton Shana M

2012-10-01

Full Text Available Abstract Background Glutathione (GSH/glutathione disulfide (GSSG and cysteine (Cys/cystine (CySS are major redox pools with important roles in cytoprotection. We determined the impact of septic peritonitis on thiol-disulfide redox status in mice. Methods FVB/N mice (6–12 week old; 8/group underwent laparotomy with cecal ligation and puncture (CLP or laparotomy alone (control. Sections of ileum, colon, lung and liver were obtained and GSH, GSSG, Cys and CySS concentrations determined by HPLC 24 h after laparotomy. Redox potential [Eh in millivolts (mV] of the GSH/GSSG and Cys/CySS pools was calculated using the Nernst equation. Data were analyzed by ANOVA (mean ± SE. Results GSH/GSSG Eh in ileum, colon, and liver was significantly oxidized in septic mice versus control mice (ileum: septic −202±4 versus control −228±2 mV; colon: -195±8 versus −214±1 mV; and liver: -194±3 vs. -210±1 mV, all Ph was unchanged with CLP, while liver and lung Cys/CySS Eh became significantly more reducing (liver: septic = −103±3 versus control −90±2 mV; lung: -101±5 versus −81±1 mV, each P Conclusions Septic peritonitis induced by CLP oxidizes ileal and colonic GSH/GSSG redox but Cys/CySS Eh remains unchanged in these intestinal tissues. In liver, CLP oxidizes the GSH/GSSG redox pool and CyS/CySS Eh becomes more reducing; in lung, CLP does not alter GSH/GSSG Eh, and Cys/CySS Eh is less oxidized. CLP-induced infection/inflammation differentially regulates major thiol-disulfide redox pools in this murine model.

Glutathione regulation of redox-sensitive signals in tumor necrosis factor-α-induced vascular endothelial dysfunction

International Nuclear Information System (INIS)

Tsou, T.-C.; Yeh, S.C.; Tsai, F.-Y.; Chen, J.-W.; Chiang, H.-C.

2007-01-01

We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-α)-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-α induces various biological effects on vascular cells, TNF-α dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-α concentrations, we adopted the lower TNF-α (0.2 ng/ml) to rule out the possible involvement of other TNF-α-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-α-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-α-induced nuclear factor-kappaB (NF-κB) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-α. Inhibition of ERK, JNK, or NF-κB attenuates TNF-α-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-α induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-κB in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-α. Although AP-1 activation by the lower TNF-α was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-α-induced adhesion molecule expression

Efficient cycles for carbon capture CLC power plants based on thermally balanced redox reactors

KAUST Repository

Iloeje, Chukwunwike

2015-10-01

© 2015 Elsevier Ltd. The rotary reactor differs from most alternative chemical looping combustion (CLC) reactor designs because it maintains near-thermal equilibrium between the two stages of the redox process by thermally coupling channels undergoing oxidation and reduction. An earlier study showed that this thermal coupling between the oxidation and reduction reactors increases the efficiency by up to 2% points when implemented in a regenerative Brayton cycle. The present study extends this analysis to alternative CLC cycles with the objective of identifying optimal configurations and design tradeoffs. Results show that the increased efficiency from reactor thermal coupling applies only to cycles that are capable of exploiting the increased availability in the reduction reactor exhaust. Thus, in addition to the regenerative cycle, the combined CLC cycle and the combined-regenerative CLC cycle are suitable for integration with the rotary reactor. Parametric studies are used to compare the sensitivity of the different cycle efficiencies to parameters like pressure ratio, turbine inlet temperature, carrier-gas fraction and purge steam generation. One of the key conclusions from this analysis is that while the optimal efficiency for regenerative CLC cycle was the highest of the three (56% at 3. bars, 1200. °C), the combined-regenerative cycle offers a trade-off that combines a reasonably high efficiency (about 54% at 12. bars, 1200. °C) with much lower gas volumetric flow rate and consequently, smaller reactor size. Unlike the other two cycles, the optimal compressor pressure ratio for the regenerative cycle is weakly dependent on the design turbine inlet temperature. For the regenerative and combined regenerative cycles, steam production in the regenerator below 2× fuel flow rate improves exhaust recovery and consequently, the overall system efficiency. Also, given that the fuel side regenerator flow is unbalanced, it is more efficient to generate steam from the

Extracellular redox state: refining the definition of oxidative stress in aging.

Science.gov (United States)

Jones, Dean P

2006-01-01

Oxidative stress in aging can result from an imbalance of prooxidants and antioxidants with excessive, destructive free radical chemistry. Thiol systems are important in the control of these processes, both by protecting against damage and serving in redox signaling mechanisms to sense danger and repair the damage. Studies by a number of research groups in collaboration with the Emory Clinical Biomarkers Laboratory show that the redox state of the central tissue antioxidant, glutathione (GSH), can be measured in human plasma and provides a quantitative systemic indicator of oxidative stress. Plasma GSH/GSSG redox in humans becomes oxidized with age, in response to chemotherapy, as a consequence of cigarette smoking, and in association with common age-related diseases (e.g., type 2 diabetes, cardiovascular disease). However, the GSH/GSSG redox is not equilibrated with the larger plasma cysteine/cystine (Cys/CySS) pool, and the Cys/CySS redox varies with age in a pattern that is distinct from that of GSH/GSSG redox. Furthermore, in vitro studies show that variation in Cys/CySS redox over the range found in vivo affects signaling pathways, which control cell proliferation and oxidant-induced apoptosis. The results point to the conclusion that free radical scavenging antioxidants are of increased importance when thiol/disulfide redox states are oxidized. Because thiol/disulfide redox states, per se, function in redox signaling and control as well as antioxidant protection, GSH/GSSG and Cys/CySS redox states may provide central parameters to link environmental influences and progression of changes associated with aging.

Long-term litter decomposition controlled by manganese redox cycling.

Science.gov (United States)

Keiluweit, Marco; Nico, Peter; Harmon, Mark E; Mao, Jingdong; Pett-Ridge, Jennifer; Kleber, Markus

2015-09-22

Litter decomposition is a keystone ecosystem process impacting nutrient cycling and productivity, soil properties, and the terrestrial carbon (C) balance, but the factors regulating decomposition rate are still poorly understood. Traditional models assume that the rate is controlled by litter quality, relying on parameters such as lignin content as predictors. However, a strong correlation has been observed between the manganese (Mn) content of litter and decomposition rates across a variety of forest ecosystems. Here, we show that long-term litter decomposition in forest ecosystems is tightly coupled to Mn redox cycling. Over 7 years of litter decomposition, microbial transformation of litter was paralleled by variations in Mn oxidation state and concentration. A detailed chemical imaging analysis of the litter revealed that fungi recruit and redistribute unreactive Mn(2+) provided by fresh plant litter to produce oxidative Mn(3+) species at sites of active decay, with Mn eventually accumulating as insoluble Mn(3+/4+) oxides. Formation of reactive Mn(3+) species coincided with the generation of aromatic oxidation products, providing direct proof of the previously posited role of Mn(3+)-based oxidizers in the breakdown of litter. Our results suggest that the litter-decomposing machinery at our coniferous forest site depends on the ability of plants and microbes to supply, accumulate, and regenerate short-lived Mn(3+) species in the litter layer. This observation indicates that biogeochemical constraints on bioavailability, mobility, and reactivity of Mn in the plant-soil system may have a profound impact on litter decomposition rates.

Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes

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Jaime Franco

2017-12-01

Full Text Available With the aim to develop compounds able to target multiple metabolic pathways and, thus, to lower the chances of drug resistance, we investigated the anti-trypanosomal activity and selectivity of a series of symmetric diglycosyl diselenides and disulfides. Of 18 compounds tested the fully acetylated forms of di-β-D-glucopyranosyl and di-β-D-galactopyranosyl diselenides (13 and 15, respectively displayed strong growth inhibition against the bloodstream stage of African trypanosomes (EC50 0.54 μM for 13 and 1.49 μM for 15 although with rather low selectivity (SI < 10 assayed with murine macrophages. Nonacetylated versions of the same sugar diselenides proved to be, however, much less efficient or completely inactive to suppress trypanosome growth. Significantly, the galactosyl (15, and to a minor extent the glucosyl (13, derivative inhibited glucose catabolism but not its uptake. Both compounds induced redox unbalance in the pathogen. In vitro NMR analysis indicated that diglycosyl diselenides react with glutathione, under physiological conditions, via formation of selenenylsulfide bonds. Our results suggest that non-specific cellular targets as well as actors of the glucose and the redox metabolism of the parasite may be affected. These molecules are therefore promising leads for the development of novel multitarget antitrypanosomal agents. Keywords: Glutathione, Redox biosensor, Selenosugar, Trypanosome inhibition, Selenium NMR

Glutathione S - transferases class Pi and Mi and their significance in oncology

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Zofia Marchewka

2017-06-01

Full Text Available In this article the current data, which shows that glutathione S-transferases (GST class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

Glutathione S - transferases class Pi and Mi and their significance in oncology.

Science.gov (United States)

Marchewka, Zofia; Piwowar, Agnieszka; Ruzik, Sylwia; Długosz, Anna

2017-06-19

In this article the current data, which shows that glutathione S-transferases (GST) class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi) in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

Effect of long-term fertilization on humic redox mediators in multiple microbial redox reactions.

Science.gov (United States)

Guo, Peng; Zhang, Chunfang; Wang, Yi; Yu, Xinwei; Zhang, Zhichao; Zhang, Dongdong

2018-03-01

This study investigated the effects of different long-term fertilizations on humic substances (HSs), humic acids (HAs) and humins, functioning as redox mediators for various microbial redox biotransformations, including 2,2',4,4',5,5'- hexachlorobiphenyl (PCB 153 ) dechlorination, dissimilatory iron reduction, and nitrate reduction, and their electron-mediating natures. The redox activity of HSs for various microbial redox metabolisms was substantially enhanced by long-term application of organic fertilizer (pig manure). As a redox mediator, only humin extracted from soils with organic fertilizer amendment (OF-HM) maintained microbial PCB 153 dechlorination activity (1.03 μM PCB 153 removal), and corresponding HA (OF-HA) most effectively enhanced iron reduction and nitrate reduction by Shewanella putrefaciens. Electrochemical analysis confirmed the enhancement of their electron transfer capacity and redox properties. Fourier transform infrared analysis showed that C=C and C=O bonds, and carboxylic or phenolic groups in HSs might be the redox functional groups affected by fertilization. This research enhances our understanding of the influence of anthropogenic fertility on the biogeochemical cycling of elements and in situ remediation ability in agroecosystems through microorganisms' metabolisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrologic influence on redox dynamics in estuarine environments

Science.gov (United States)

Michael, H. A.; Kim, K. H.; Guimond, J. A.; Heiss, J.; Ullman, W. J.; Seyfferth, A.

2017-12-01

Redox conditions in coastal aquifers control reactions that impact nutrient cycling, contaminant release, and carbon budgets, with implications for water resources and ecosystem health. Hydrologic changes can shift redox boundaries and inputs of reactants, especially in dynamic coastal systems subject to fluctuations on tidal, lunar, and longer timescales. We present two examples of redox shifts in estuarine systems in Delaware, USA: a beach aquifer and a saltmarsh. Beach aquifers are biogeochemical hot spots due to mixing between fresh groundwater and infiltrating seawater. At Cape Henlopen, DE, geochemical measurements identified reactions in the intertidal aquifer that include cycling of carbon, nitrogen, iron, and sulfur. Measurements and modeling illustrate that redox potential as well as the locations of redox reactions shift on tidal to seasonal timescales and in response to changing beach and aquifer properties, impacting overall rates of reactions such as denitrification that reduces N loads to coastal waters. In the St. Jones National Estuarine Research Reserve, tidal fluctuations in channels cause periodic groundwater-surface water exchange, water table movement, and intermittent flooding that varies spatially across the saltmarsh. These changes create shifts in redox potential that are greatest near channels and in the top 20 cm of sediments. The magnitude of redox change depends on hydrologic setting (near channels or in marsh interior), hydrologic conditions (tidal stage, seasonal shifts), as well as prevalence of macropores created by crab burrows that change seasonally with crab activity. These shifts correspond to changes in porewater chemistry that have implications for nutrient cycling and carbon export to the ocean. Understanding hydrologic influence on redox geochemistry is critical for predicting how these systems and their ecosystem services may change in the future in response to anthropogenic and climate change.

OXIDATIVE MODIFICATION OF PROTEINS AND GLUTATHIONE SYSTEM IN ADIPOCYTES UNDER DIABETES

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Ye. V. Shakhristova

2014-01-01

Full Text Available Currently, diabetes ranks third in relation to medical and social significance after cardiovascular diseases and cancer and is the leading cause of blindness; it greatly increases the risk of myocardial infarction, coronary heart disease, nephropathy and hypertension in patients with this disorder; therefore clinical and experimental studies aimed at investigation of diabetes emergence and development mechanisms are urgent.The aim of the study was to investigate the status of oxidative modification of proteins and glutathionedependent antioxidant defense system in adipocytes of rats with alloxan diabetes under conditions of oxidative stress.Material and methods. Development of type 1 diabetes was induced in rats by alloxan administration (90 mg/kg of body mass. Adipocytes were obtained from epididymal adipose tissue of rats. The level of carbonyl derivatives of proteins, oxidized tryptophan, bityrosine, general, reduced, oxygenated and protein-bound glutathione, as well as glutathione peroxidase activity in adipocytes of rats was determined.Results. In adipocytes of rats with alloxan diabetes, concentration of carbonyl derivatives of proteins, bityrosine and oxidized tryptophan increased on the background of redox-potential of glutathione system and glutathione peroxidase activity decrease.Conclusion. The obtained data indicate the activation of free-radical oxidation of proteins and reduction of antioxidant defense under conditions of oxidative stress in the adipose tissue of rats with alloxan diabetes; this process plays an important role in pathogenesis of diabetes and its complications development.

Redox Stable Anodes for Solid Oxide Fuel Cells

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Guoliang eXiao

2014-06-01

Full Text Available Solid oxide fuel cells (SOFCs can convert chemical energy from the fuel directly to electrical energy with high efficiency and fuel flexibility. Ni-based cermets have been the most widely adopted anode for SOFCs. However, the conventional Ni-based anode has low tolerance to sulfur-contamination, is vulnerable to deactivation by carbon build-up (coking from direct oxidation of hydrocarbon fuels, and suffers volume instability upon redox cycling. Among these limitations, the redox instability of the anode is particularly important and has been intensively studied since the SOFC anode may experience redox cycling during fuel cell operations even with the ideal pure hydrogen as the fuel. This review aims to highlight recent progresses on improving redox stability of the conventional Ni-based anode through microstructure optimization and exploration of alternative ceramic-based anode materials.

Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

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Anna E. Maciag

2013-01-01

Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

Dimethylfumarate induces cell cycle arrest and apoptosis via regulating intracellular redox systems in HeLa cells.

Science.gov (United States)

Han, Guocan; Zhou, Qiang

2016-12-01

Dimethylfumarate (DMF) is cytotoxic to several kinds of cells and serves as an anti-tumor drug. This study was designed to investigate the effects and underlying mechanism of DMF on cervical cancer cells. HeLa cells were cultured and treated with 0, 50, 100, 150, and 200 μM DMF, respectively. After 24 h, cell growth was evaluated using Cell Counting Kit-8 (CCK-8) assay and the cell cycle was examined using flow cytometry. In addition, cell apoptosis was detected by Annexin V/propidium iodide (PI) staining and the expressions of caspase-3 and poly-ADP-ribose polymerase (PARP) were detected using western blotting. The redox-related factors were then assessed. Furthermore, all of the indicators were detected in HeLa cells after combined treatment of DMF and N-acetyl-L-cysteine (NAC, an oxygen-free radical scavenger). The cell number and cell growth of HeLa were obviously inhibited by DMF in a dose-dependent manner, as the cell cycle was arrested at G0/G1 phase (P HeLa cells were markedly increased, and the expression levels of caspase-3 and PARP were significantly increased in a DMF concentration-dependent way (P cell proliferation and apoptosis of HeLa cells was mainly related to the intracellular redox systems by depletion of intracellular GSH.

Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents

International Nuclear Information System (INIS)

Higgins, Larry G.; Kelleher, Michael O.; Eggleston, Ian M.; Itoh, Ken; Yamamoto, Masayuki; Hayes, John D.

2009-01-01

Sulforaphane can stimulate cellular adaptation to redox stressors through transcription factor Nrf2. Using mouse embryonic fibroblasts (MEFs) as a model, we show herein that the normal homeostatic level of glutathione in Nrf2 -/- MEFs was only 20% of that in their wild-type counterparts. Furthermore, the rate of glutathione synthesis following its acute depletion upon treatment with 3 μmol/l sulforaphane was very substantially lower in Nrf2 -/- MEFs than in wild-type cells, and the rebound leading to a ∼ 1.9-fold increase in glutathione that occurred 12-24 h after Nrf2 +/+ MEFs were treated with sulforaphane was not observed in Nrf2 -/- fibroblasts. Wild-type MEFs that had been pre-treated for 24 h with 3 μmol/l sulforaphane exhibited between 1.4- and 3.2-fold resistance against thiol-reactive electrophiles, including isothiocyanates, α,β-unsaturated carbonyl compounds (e.g. acrolein), aryl halides and alkene epoxides. Pre-treatment of Nrf2 +/+ MEFs with sulforaphane also protected against hydroperoxides (e.g. cumene hydroperoxide, CuOOH), free radical-generating compounds (e.g. menadione), and genotoxic electrophiles (e.g. chlorambucil). By contrast, Nrf2 -/- MEFs were typically ∼ 50% less tolerant of these agents than wild-type fibroblasts, and sulforaphane pre-treatment did not protect the mutant cells against xenobiotics. To test whether Nrf2-mediated up-regulation of glutathione represents the major cytoprotective mechanism stimulated by sulforaphane, 5 μmol/l buthionine sulfoximine (BSO) was used to inhibit glutathione synthesis. In Nrf2 +/+ MEFs pre-treated with sulforaphane, BSO diminished intrinsic resistance and abolished inducible resistance to acrolein, CuOOH and chlorambucil, but not menadione. Thus Nrf2-dependent up-regulation of GSH is the principal mechanism by which sulforaphane pre-treatment induced resistance to acrolein, CuOOH and chlorambucil, but not menadione.

Thiol-based redox signaling in the nitrogen-fixing symbiosis

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Pierre eFrendo

2013-09-01

Full Text Available In nitrogen poor soils legumes establish a symbiotic interaction with rhizobia that results in the formation of root nodules. These are unique plant organs where bacteria differentiate into bacteroids, which express the nitrogenase enzyme complex that reduces atmospheric N2 to ammonia. Nodule metabolism requires a tight control of the concentrations of reactive oxygen and nitrogen species (RONS so that they can perform useful signaling roles while avoiding nitro-oxidative damage. In nodules a thiol-dependent regulatory network that senses, transmits and responds to redox changes is starting to be elucidated. A combination of enzymatic, immunological, pharmacological and molecular analyses has allowed to conclude that glutathione and its legume-specific homolog, homoglutathione, are abundant in meristematic and infected cells, their spatio-temporally distribution is correlated with the corresponding (homoglutathione synthetase activities, and are crucial for nodule development and function. Glutathione is at high concentrations in the bacteroids and at moderate amounts in the mitochondria, cytosol and nuclei. Less information is available on other components of the network. The expression of multiple isoforms of glutathione peroxidases, peroxiredoxins, thioredoxins, glutaredoxins and NADPH-thioredoxin reductases has been detected in nodule cells using antibodies and proteomics. Peroxiredoxins and thioredoxins are essential to regulate and in some cases to detoxify RONS in nodules. Further research is necessary to clarify the regulation of the expression and activity of thiol redox-active proteins in response to abiotic, biotic and developmental cues, their interactions with downstream targets by disulfide-exchange reactions, and their participation in signaling cascades. The availability of mutants and transgenic lines will be crucial to facilitate systematic investigations into the function of the various proteins in the legume

The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).

Science.gov (United States)

Salinas, Gustavo; Gao, Wei; Wang, Yang; Bonilla, Mariana; Yu, Long; Novikov, Andrey; Virginio, Veridiana G; Ferreira, Henrique B; Vieites, Marisol; Gladyshev, Vadim N; Gambino, Dinorah; Dai, Shaodong

2017-12-20

New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with Au I -MPO, a novel gold inhibitor, together with inhibition assays were performed. Au I -MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer-monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys 519 and Cys 573 in the Au I -TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys 519 and Cys 573 residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491-1504.

Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alterations in CNS Development

Science.gov (United States)

2012-10-01

inflammatory response. As a marker of oxidative stress, elevated levels of nitrotyrosine have been found in alcoholics, smokers, diabetes , athero- sclerosis...Jones, J. L. Carlson, V. C. Mody , J. Cai, M. J. Lynn, and P. Sternberg, “Redox state of glutathione in human plasma,” Free Radical Biology and Medicine

Changes in Athlete’s Redox State Induced by Habitual and Unaccustomed Exercise

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Dusica Z. Djordjevic

2012-01-01

Full Text Available The purpose of this study was to assess the influence of sport-specific and nonspecific bouts of exercise on athletes’ redox state. Blood samples were collected from 14 handball players immediately before and after graded exercise test on the cycle ergometer and handball training. Levels of superoxide anion radical (O2-, hydrogen peroxide (H2O2, nitrites (NO2- as markers of nitric oxide, index of lipid peroxidation (TBARs, glutathione (GSH, superoxide dismutase (SOD, and catalase (CAT activity were determined. Exercise intensity was assessed by a system for heart rate (HR monitoring. Average athletes’ HR was not significantly different between protocols, but protocols differed in total time and time and percentage of time that athletes spent in every HR zone. The laboratory exercise test induced a significant increase of H2O2 and TBARs as well as the decrease of the SOD and CAT activity, while after specific handball training, levels of NO2- were increased and SOD activity decreased. It seems that unaccustomed short intensive physical activity may induce oxidative stress in trained athletes, while sport-specific activity of longer duration and proper warm-up period may not. Further research should show whether the change of protocol testing and the implementation of various supplementations and manual methods can affect the redox equilibrium.

Redox regulation in photosynthetic organisms: signaling, acclimation, and practical implications.

Science.gov (United States)

Foyer, Christine H; Noctor, Graham

2009-04-01

Reactive oxygen species (ROS) have multifaceted roles in the orchestration of plant gene expression and gene-product regulation. Cellular redox homeostasis is considered to be an "integrator" of information from metabolism and the environment controlling plant growth and acclimation responses, as well as cell suicide events. The different ROS forms influence gene expression in specific and sometimes antagonistic ways. Low molecular antioxidants (e.g., ascorbate, glutathione) serve not only to limit the lifetime of the ROS signals but also to participate in an extensive range of other redox signaling and regulatory functions. In contrast to the low molecular weight antioxidants, the "redox" states of components involved in photosynthesis such as plastoquinone show rapid and often transient shifts in response to changes in light and other environmental signals. Whereas both types of "redox regulation" are intimately linked through the thioredoxin, peroxiredoxin, and pyridine nucleotide pools, they also act independently of each other to achieve overall energy balance between energy-producing and energy-utilizing pathways. This review focuses on current knowledge of the pathways of redox regulation, with discussion of the somewhat juxtaposed hypotheses of "oxidative damage" versus "oxidative signaling," within the wider context of physiological function, from plant cell biology to potential applications.

Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression.

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Valeria Gabriela Antico Arciuch

2009-10-01

Full Text Available Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser(473 by mTORC2 and Thr(308 by PDK1. On these bases, we investigated the mechanistic connection of H(2O(2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H(2O(2 entails the entrance of cytosolic P-Akt1 Ser(473 to mitochondria, where it is further phosphorylated at Thr(308 by constitutive PDK1. Phosphorylation of Thr(308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H(2O(2, Akt1-PDK1 association is disrupted and P-Akt1 Ser(473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H(2O(2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys(310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.

[Effect of extremely low frequency magnetic field on glutathione in rat muscles].

Science.gov (United States)

Ciejka, Elzbieta; Jakubowska, Ewa; Zelechowska, Paulina; Huk-Kolega, Halina; Kowalczyk, Agata; Goraca, Anna

2014-01-01

Free radicals (FR) are atoms, molecules or their fragments. Their excess leads to the development of oxidizing stress, the cause of many neoplastic, neurodegenerative and inflammatory diseases, and aging of the organism. Industrial pollution, tobacco smoke, ionizing radiation, ultrasound and magnetic field are the major FR exogenous sources. The low frequency magnetic field is still more commonly applied in the physical therapy. The aim of the presented study was to evaluate the effect of extremely low frequency magnetic field used in the magnetotherapy on the level of total glutathione, oxidized and reduced, and the redox state of the skeletal muscle cells, depending on the duration of exposure to magnetic field. The male rats, weight of 280-300 g, were randomly devided into 3 experimental groups: controls (group I) and treatment groups exposed to extremely low frequency magnetic field (ELF-MF) (group II exposed to 40 Hz, 7 mT for 0.5 h/day for 14 days and group III exposed to 40 Hz, 7 mT for 1 h/day for 14 days). Control rats were kept in a separate room not exposed to extremely low frequency magnetic field. Immediately after the last exposure, part of muscles was taken under pentobarbital anesthesia. Total glutathione, oxidized and reduced, and the redox state in the muscle tissue of animals were determined after exposure to magnetic fields. Exposure to low magnetic field: 40 Hz, 7 mT for 30 min/day and 60 min/day for 2 weeks significantly increased the total glutathione levels in the skeletal muscle compared to the control group (p magnetic therapy plays an important role in the development of adaptive mechanisms responsible for maintaining the oxidation-reduction balance in the body and depends on exposure duration.

1-Methyl-4-phenylpyridinium-induced alterations of glutathione status in immortalized rat dopaminergic neurons

International Nuclear Information System (INIS)

Drechsel, Derek A.; Liang, L.-P.; Patel, Manisha

2007-01-01

Decreased glutathione levels associated with increased oxidative stress are a hallmark of numerous neurodegenerative diseases, including Parkinson's disease. GSH is an important molecule that serves as an anti-oxidant and is also a major determinant of cellular redox environment. Previous studies have demonstrated that neurotoxins can cause changes in reduced and oxidized GSH levels; however, information regarding steady state levels remains unexplored. The goal of this study was to characterize changes in cellular GSH levels and its regulatory enzymes in a dopaminergic cell line (N27) following treatment with the Parkinsonian toxin, 1-methyl-4-phenylpyridinium (MPP + ). Cellular GSH levels were initially significantly decreased 12 h after treatment, but subsequently recovered to values greater than controls by 24 h. However, oxidized glutathione (GSSG) levels were increased 24 h following treatment, concomitant with a decrease in GSH/GSSG ratio prior to cell death. In accordance with these changes, ROS levels were also increased, confirming the presence of oxidative stress. Decreased enzymatic activities of glutathione reductase and glutamate-cysteine ligase by 20-25% were observed at early time points and partly account for changes in GSH levels after MPP + exposure. Additionally, glutathione peroxidase activity was increased 24 h following treatment. MPP + treatment was not associated with increased efflux of glutathione to the medium. These data further elucidate the mechanisms underlying GSH depletion in response to the Parkinsonian toxin, MPP +

Role of a redox-based methylation switch in mRNA life cycle ( pre- & post- transcriptional maturation and protein turnover : Implications in neurological disorders

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MALAV SUCHIN TRIVEDI

2012-06-01

Full Text Available Homeostatic synaptic scaling in response to neuronal stimulus or activation, as well as due to changes in cellular niche, is an important phenomenon for memory consolidation, retrieval, and other similar cognitive functions. Neurological disorders and cognitive disabilities in autism, Rett syndrome, schizophrenia, dementia etc., are strongly correlated to alterations in protein expression (both synaptic and cytoplasmic. This correlation suggests that efficient temporal regulation of synaptic protein expression is important for synaptic plasticity. In addition, equilibrium between mRNA processing, protein translation and protein turnover is a critical sensor/trigger for recording synaptic information, normal cognition and behavior. Thus a regulatory switch, controlling the lifespan, maturation and processing of mRNA, might influence cognition and adaptive behavior. Here, we propose a two part novel hypothesis that methylation might act as this suggested coordinating switch to critically regulate mRNA maturation at 1.The pre-transcription level, by regulating precursor-RNA (pre-RNA processing into mRNA, via other non-coding RNAs and their influence on splicing phenomenon, and 2. the post-transcription level by modulating the regulatory functions of ribonucleoproteins (RNP and RNA binding proteins (RNABP in mRNA translation, dendritic translocation as well as protein synthesis and synaptic turnover. DNA methylation changes are well recognized and highly correlated to gene expression levels as well as, learning and memory; however, RNA methylation changes are recently characterized and yet their functional implications are not established. This review article provides some insight on the intriguing consequences of changes in methylation levels on mRNA life-cycle. We also suggest that, since methylation is under the control of glutathione antioxidant levels, the redox status of neurons might be the central regulatory switch for methylation

Powering Lithium-Sulfur Battery Performance by Propelling Polysulfide Redox at Sulfiphilic Hosts.

Science.gov (United States)

Yuan, Zhe; Peng, Hong-Jie; Hou, Ting-Zheng; Huang, Jia-Qi; Chen, Cheng-Meng; Wang, Dai-Wei; Cheng, Xin-Bing; Wei, Fei; Zhang, Qiang

2016-01-13

Lithium-sulfur (Li-S) battery system is endowed with tremendous energy density, resulting from the complex sulfur electrochemistry involving multielectron redox reactions and phase transformations. Originated from the slow redox kinetics of polysulfide intermediates, the flood of polysulfides in the batteries during cycling induced low sulfur utilization, severe polarization, low energy efficiency, deteriorated polysulfide shuttle, and short cycling life. Herein, sulfiphilic cobalt disulfide (CoS2) was incorporated into carbon/sulfur cathodes, introducing strong interaction between lithium polysulfides and CoS2 under working conditions. The interfaces between CoS2 and electrolyte served as strong adsorption and activation sites for polar polysulfides and therefore accelerated redox reactions of polysulfides. The high polysulfide reactivity not only guaranteed effective polarization mitigation and promoted energy efficiency by 10% but also promised high discharge capacity and stable cycling performance during 2000 cycles. A slow capacity decay rate of 0.034%/cycle at 2.0 C and a high initial capacity of 1368 mAh g(-1) at 0.5 C were achieved. Since the propelling redox reaction is not limited to Li-S system, we foresee the reported strategy herein can be applied in other high-power devices through the systems with controllable redox reactions.

Hexamethoxylated Monocarbonyl Analogues of Curcumin Cause G2/M Cell Cycle Arrest in NCI-H460 Cells via Michael Acceptor-Dependent Redox Intervention.

Science.gov (United States)

Li, Yan; Zhang, Li-Ping; Dai, Fang; Yan, Wen-Jing; Wang, Hai-Bo; Tu, Zhi-Shan; Zhou, Bo

2015-09-09

Curcumin, derived from the dietary spice turmeric, holds promise for cancer prevention. This prompts much interest in investigating the action mechanisms of curcumin and its analogues. Two symmetrical hexamethoxy-diarylpentadienones (1 and 2) as cucumin analogues were reported to possess significantly enhanced cytotoxicity compared with the parent molecule. However, the detailed mechanisms remain unclear. In this study, compounds 1 and 2 were identified as the G2/M cell cycle arrest agents to mediate the cytotoxicity toward NCI-H460 cells via Michael acceptor-dependent redox intervention. Compared with curcumin, they could more easily induce a burst of reactive oxygen species (ROS) and collapse of the redox buffering system. One possible reason is that they could more effectively target intracellular TrxR to convert this antioxidant enzyme into a ROS promoter. Additionally, they caused up-regulation of p53 and p21 and down-regulation of redox-sensitive Cdc25C along with cyclin B1/Cdk1 in a Michael acceptor- and ROS-dependent fashion. Interestingly, in comparison with compound 2, compound 1 displayed a relatively weak ability to generate ROS but increased cell cycle arrest activity and cytotoxicity probably due to its Michael acceptor-dependent microtubule-destabilizing effect and greater GST-inhibitory activity, as well as its enhanced cellular uptake. This work provides useful information for understanding Michael acceptor-dependent and redox-mediated cytotoxic mechanisms of curcumin and its active analogues.

A multi-electron redox mediator for redox-targeting lithium-sulfur flow batteries

Science.gov (United States)

Li, Guochun; Yang, Liuqing; Jiang, Xi; Zhang, Tianran; Lin, Haibin; Yao, Qiaofeng; Lee, Jim Yang

2018-02-01

The lithium-sulfur flow battery (LSFB) is a new addition to the rechargeable lithium flow batteries (LFBs) where sulfur or a sulfur compound is used as the cathode material against the lithium anode. We report here our evaluation of an organic sulfide - dimethyl trisulfide (DMTS), as 1) a catholyte of a LFB and 2) a multi-electron redox mediator for discharging and charging a solid sulfur cathode without any conductive additives. The latter configuration is also known as the redox-targeting lithium-sulfur flow battery (RTLSFB). The LFB provides an initial discharge capacity of 131.5 mAh g-1DMTS (1.66 A h L-1), which decreases to 59 mAh g-1DMTS (0.75 A h L-1) after 40 cycles. The RTLSFB delivers a significantly higher application performance - initial discharge capacity of 1225.3 mAh g-1sulfur (3.83 A h L-1), for which 1030.9 mAh g-1sulfur (3.23 A h L-1) is still available after 40 cycles. The significant increase in the discharge and charge duration of the LFB after sulfur addition indicates that DMTS is better used as a redox mediator in a RTLSFB than as a catholyte in a LFB.

How Reducing was the Late Devonian Ocean? The Role of Extensive Expansion of Anoxia in Marine Biogeochemical Cycles of Redox Sensitive Metals.

Science.gov (United States)

Sahoo, S. K.; Jin, H.

2017-12-01

The evolution of Earth's biogeochemical cycles is intimately linked to the oxygenation of the oceans and atmosphere. The Late Devonian is no exception as its characterized with mass extinction and severe euxinia. Here we use concentrations of Molybdenum (Mo), Vanadium (V), Uranium (U) and Chromium (Cr) in organic rich black shales from the Lower Bakken Formation of the Williston Basin, to explore the relationship between extensive anoxia vs. euxinia and it's relation with massive release of oxygen in the ocean atmosphere system. XRF data from 4 core across the basin shows that modern ocean style Mo, U and Cr enrichments are observed throughout the Lower Bakken Formation, yet V is not enriched until later part of the formation. Given the coupling between redox-sensitive-trace element cycles and ocean redox, various models for Late Devonian ocean chemistry imply different effects on the biogeochemical cycling of major and trace nutrients. Here, we examine the differing redox behavior of molybdenum and vanadium under an extreme anoxia and relatively low extent of euxinia. The model suggests that Late Devonian was perhaps extensively anoxic- 40-50% compared to modern seafloor area, and a very little euxinia. Mo enrichments extend up to 500 p.p.m. throughout the section, representative of a modern reducing ocean. However, coeval low V enrichments only support towards anoxia, where anoxia is a source of V, and a sink for Mo. Our model suggests that the oceanic V reservoir is extremely sensitive to perturbations in the extent of anoxic condition, particularly during post glacial times.

Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication.

Science.gov (United States)

Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

2015-10-01

Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. Copyright © 2015 Elsevier Inc. All rights reserved.

Glutathione and its dependent enzymes' modulatory responses to toxic metals and metalloids in fish--a review.

Science.gov (United States)

Srikanth, K; Pereira, E; Duarte, A C; Ahmad, I

2013-04-01

Toxic metals and metalloid are being rapidly added from multiple pathways to aquatic ecosystem and causing severe threats to inhabiting fauna including fish. Being common in all the type of aquatic ecosystems such as freshwater, marine and brackish water fish are the first to get prone to toxic metals and metalloids. In addition to a number of physiological/biochemical alterations, toxic metals and metalloids cause enhanced generation of varied reactive oxygen species (ROS) ultimately leading to a situation called oxidative stress. However, as an important component of antioxidant defence system in fish, the tripeptide glutathione (GSH) directly or indirectly regulates the scavenging of ROS and their reaction products. Additionally, several other GSH-associated enzymes such as GSH reductase (GR, EC 1.6.4.2), GSH peroxidase (EC 1.11.1.9), and GSH sulfotransferase (glutathione-S-transferase (GST), EC 2.5.1.18) cumulatively protect fish against ROS and their reaction products accrued anomalies under toxic metals and metalloids stress conditions. The current review highlights recent research findings on the modulation of GSH, its redox couple (reduced glutathione/oxidised glutathione), and other GSH-related enzymes (GR, glutathione peroxidase, GST) involved in the detoxification of harmful ROS and their reaction products in toxic metals and metalloids-exposed fish.

Redox non-innocent ligands: versatile new tools to control catalytic reactions

NARCIS (Netherlands)

Lyaskovskyy, V.; de Bruin, B.

2012-01-01

In this (tutorial overview) perspective we highlight the use of "redox non-innocent" ligands in catalysis. Two main types of reactivity in which the redox non-innocent ligand is involved can be specified: (A) The redox active ligand participates in the catalytic cycle only by accepting/donating

Unacylated ghrelin does not alter mitochondrial function, redox state and triglyceride content in rat liver in vivo

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Gianluca Gortan Cappellari

2015-12-01

Full Text Available Changes in liver mitochondrial function with more oxidized redox state and enhanced inflammation may contribute to the onset of obesity- and insulin resistance-associated hepatic complications, including non-alcoholic fatty liver disease and steato-hepatitis. Unacylated ghrelin (UnAG is a gastric hormone reported to be associated with lower oxidative stress in different cell types, but its potential effects on liver mitochondrial function, redox state and inflammation in vivo remains undetermined. We investigated the impact of chronic UnAG overexpression (Tg Myh6/Ghrl leading to systemic upregulation of circulating hormone on mitochondrial ATP production, redox state (oxidized-to-total glutathione and inflammation markers in lean mice. Compared to wild-type animals (wt, Tg Myh6/Ghrl had superimposable liver weight, triglyceride content and plasma lipid profile. Liver mitochondrial enzyme activities and ATP production as well as oxidized-to-total glutathione were also similar in the two groups. In addition, no differences were observed in tissue inflammation marker TNF-alpha between wild-type and Tg Myh6/Ghrl animals. Thus, chronic systemic UnAG upregulation does not alter liver triglyceride content, mitochondrial function, redox state and inflammation markers in lean mice. These findings do not support a major role of UnAG as a physiological modulator of in vivo liver oxidative-lipid metabolism and inflammation.

S-Glutathionylation and Redox Protein Signaling in Drug Addiction.

Science.gov (United States)

Womersley, Jacqueline S; Uys, Joachim D

2016-01-01

Drug addiction is a chronic relapsing disorder that comes at a high cost to individuals and society. Therefore understanding the mechanisms by which drugs exert their effects is of prime importance. Drugs of abuse increase the production of reactive oxygen and nitrogen species resulting in oxidative stress. This change in redox homeostasis increases the conjugation of glutathione to protein cysteine residues; a process called S-glutathionylation. Although traditionally regarded as a protective mechanism against irreversible protein oxidation, accumulated evidence suggests a more nuanced role for S-glutathionylation, namely as a mediator in redox-sensitive protein signaling. The reversible modification of protein thiols leading to alteration in function under different physiologic/pathologic conditions provides a mechanism whereby change in redox status can be translated into a functional response. As such, S-glutathionylation represents an understudied means of post-translational protein modification that may be important in the mechanisms underlying drug addiction. This review will discuss the evidence for S-glutathionylation as a redox-sensing mechanism and how this may be involved in the response to drug-induced oxidative stress. The function of S-glutathionylated proteins involved in neurotransmission, dendritic spine structure, and drug-induced behavioral outputs will be reviewed with specific reference to alcohol, cocaine, and heroin. Copyright © 2016. Published by Elsevier Inc.

Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

Science.gov (United States)

Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

2014-01-01

To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible. Copyright © 2014 Elsevier Inc. All rights reserved.

Capacitance enhancement of polyaniline coated curved-graphene supercapacitors in a redox-active electrolyte

KAUST Repository

Chen, Wei

2013-01-01

We show, for the first time, a redox-active electrolyte in combination with a polyaniline-coated curved graphene active material to achieve significant enhancement in the capacitance (36-92% increase) compared to supercapacitors that lack the redox-active contribution from the electrolyte. The supercapacitors based on the redox-active electrolyte also exhibit excellent rate capability and very long cycling performance (>50 000 cycles). This journal is © The Royal Society of Chemistry.

The use of polybenzimidazole membranes in vanadium redox flow batteries leading to increased coulombic efficiency and cycling performance

International Nuclear Information System (INIS)

Zhou, X.L.; Zhao, T.S.; An, L.; Wei, L.; Zhang, C.

2015-01-01

An issue with conventional vanadium redox flow batteries (VRFB) with Nafion membranes is the crossover of vanadium ions, resulting in low coulombic efficiency and rapid decay in capacity. In this work, a VRFB with a polybenzimidazole (PBI) membrane is tested and compared with the Nafion system. Results show that the PBI-based VRFB exhibits a substantially higher coulombic efficiency of up to 99% at current densities ranging from 20 mA cm −2 to 80 mA cm −2 . More importantly, it is demonstrated that the PBI-based VRFB has a capacity decay rate of as low as 0.3% per cycle, which is four times lower than that of the Nafion system (1.3% per cycle). The improved coulombic efficiency and cycling performance are attributed to the low crossover of vanadium ions through the PBI membrane

A novel iron-lead redox flow battery for large-scale energy storage

Science.gov (United States)

Zeng, Y. K.; Zhao, T. S.; Zhou, X. L.; Wei, L.; Ren, Y. X.

2017-04-01

The redox flow battery (RFB) is one of the most promising large-scale energy storage technologies for the massive utilization of intermittent renewables especially wind and solar energy. This work presents a novel redox flow battery that utilizes inexpensive and abundant Fe(II)/Fe(III) and Pb/Pb(II) redox couples as redox materials. Experimental results show that both the Fe(II)/Fe(III) and Pb/Pb(II) redox couples have fast electrochemical kinetics in methanesulfonic acid, and that the coulombic efficiency and energy efficiency of the battery are, respectively, as high as 96.2% and 86.2% at 40 mA cm-2. Furthermore, the battery exhibits stable performance in terms of efficiencies and discharge capacities during the cycle test. The inexpensive redox materials, fast electrochemical kinetics and stable cycle performance make the present battery a promising candidate for large-scale energy storage applications.

The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I)

Energy Technology Data Exchange (ETDEWEB)

Salinas, Gustavo [Worm Biology Lab, Institut Pasteur de Montevideo, Montevideo, Uruguay.; Cátedra de Inmunología, Facultad de Química, Instituto de Higiene, Universidad de la República, Montevideo, Uruguay.; Gao, Wei [Department of Biomedical Research, National Jewish Health, Denver, Colorado.; Department of Immunology and Microbiology, University of Colorado Denver, School of Medicine, Aurora, Colorado.; School of Science, Beijing Forestry University, Beijing, China.; Wang, Yang [Department of Biomedical Research, National Jewish Health, Denver, Colorado.; Department of Immunology and Microbiology, University of Colorado Denver, School of Medicine, Aurora, Colorado.; Bonilla, Mariana [Cátedra de Inmunología, Facultad de Química, Instituto de Higiene, Universidad de la República, Montevideo, Uruguay.; Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Uruguay.; Yu, Long [Department of Biomedical Research, National Jewish Health, Denver, Colorado.; Department of Immunology and Microbiology, University of Colorado Denver, School of Medicine, Aurora, Colorado.; Novikov, Andrey [Department of Biomedical Research, National Jewish Health, Denver, Colorado.; Department of Immunology and Microbiology, University of Colorado Denver, School of Medicine, Aurora, Colorado.; Virginio, Veridiana G. [Laboratório de Genômica Estrutural e Funcional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Ferreira, Henrique B. [Laboratório de Genômica Estrutural e Funcional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Vieites, Marisol [Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.; Gladyshev, Vadim N. [Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts.; Gambino, Dinorah [Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.; Dai, Shaodong [Department of Biomedical Research, National Jewish Health, Denver, Colorado.; Department of Immunology and Microbiology, University of Colorado Denver, School of Medicine, Aurora, Colorado.

2017-12-20

Aims: New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with AuI-MPO, a novel gold inhibitor, together with inhibition assays were performed. Results: AuI-MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer–monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys519 and Cys573 in the AuI-TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. Innovation: The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. Conclusions: The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys519 and Cys573 residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491–1504.

Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

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Alexandra Sakelliou

2016-01-01

Full Text Available We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day immediately after a muscle-damaging exercise protocol (300 eccentric contractions and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation.

The fairytale of the GSSG/GSH redox potential.

Science.gov (United States)

Flohé, Leopold

2013-05-01

The term GSSG/GSH redox potential is frequently used to explain redox regulation and other biological processes. The relevance of the GSSG/GSH redox potential as driving force of biological processes is critically discussed. It is recalled that the concentration ratio of GSSG and GSH reflects little else than a steady state, which overwhelmingly results from fast enzymatic processes utilizing, degrading or regenerating GSH. A biological GSSG/GSH redox potential, as calculated by the Nernst equation, is a deduced electrochemical parameter based on direct measurements of GSH and GSSG that are often complicated by poorly substantiated assumptions. It is considered irrelevant to the steering of any biological process. GSH-utilizing enzymes depend on the concentration of GSH, not on [GSH](2), as is predicted by the Nernst equation, and are typically not affected by GSSG. Regulatory processes involving oxidants and GSH are considered to make use of mechanistic principles known for thiol peroxidases which catalyze the oxidation of hydroperoxides by GSH by means of an enzyme substitution mechanism involving only bimolecular reaction steps. The negligibly small rate constants of related spontaneous reactions as compared with enzyme-catalyzed ones underscore the superiority of kinetic parameters over electrochemical or thermodynamic ones for an in-depth understanding of GSH-dependent biological phenomena. At best, the GSSG/GSH potential might be useful as an analytical tool to disclose disturbances in redox metabolism. This article is part of a Special Issue entitled Cellular Functions of Glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.

Microfluidic redox battery.

Science.gov (United States)

Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

2013-07-07

A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

Glutathione in Cancer Cell Death

Energy Technology Data Exchange (ETDEWEB)

Ortega, Angel L. [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain); Mena, Salvador [Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia (Spain); Estrela, Jose M., E-mail: jose.m.estrela@uv.es [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)

2011-03-11

Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.

Involvement of thiol-based mechanisms in plant development.

Science.gov (United States)

Rouhier, Nicolas; Cerveau, Delphine; Couturier, Jérémy; Reichheld, Jean-Philippe; Rey, Pascal

2015-08-01

Increasing knowledge has been recently gained regarding the redox regulation of plant developmental stages. The current state of knowledge concerning the involvement of glutathione, glutaredoxins and thioredoxins in plant development is reviewed. The control of the thiol redox status is mainly ensured by glutathione (GSH), a cysteine-containing tripeptide and by reductases sharing redox-active cysteines, glutaredoxins (GRXs) and thioredoxins (TRXs). Indeed, thiol groups present in many regulatory proteins and metabolic enzymes are prone to oxidation, ultimately leading to post-translational modifications such as disulfide bond formation or glutathionylation. This review focuses on the involvement of GSH, GRXs and TRXs in plant development. Recent studies showed that the proper functioning of root and shoot apical meristems depends on glutathione content and redox status, which regulate, among others, cell cycle and hormone-related processes. A critical role of GRXs in the formation of floral organs has been uncovered, likely through the redox regulation of TGA transcription factor activity. TRXs fulfill many functions in plant development via the regulation of embryo formation, the control of cell-to-cell communication, the mobilization of seed reserves, the biogenesis of chloroplastic structures, the metabolism of carbon and the maintenance of cell redox homeostasis. This review also highlights the tight relationships between thiols, hormones and carbon metabolism, allowing a proper development of plants in relation with the varying environment and the energy availability. GSH, GRXs and TRXs play key roles during the whole plant developmental cycle via their antioxidant functions and the redox-regulation of signaling pathways. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Redox active polymers and colloidal particles for flow batteries

Science.gov (United States)

Gavvalapalli, Nagarjuna; Moore, Jeffrey S.; Rodriguez-Lopez, Joaquin; Cheng, Kevin; Shen, Mei; Lichtenstein, Timothy

2018-05-29

The invention provides a redox flow battery comprising a microporous or nanoporous size-exclusion membrane, wherein one cell of the battery contains a redox-active polymer dissolved in the non-aqueous solvent or a redox-active colloidal particle dispersed in the non-aqueous solvent. The redox flow battery provides enhanced ionic conductivity across the electrolyte separator and reduced redox-active species crossover, thereby improving the performance and enabling widespread utilization. Redox active poly(vinylbenzyl ethylviologen) (RAPs) and redox active colloidal particles (RACs) were prepared and were found to be highly effective redox species. Controlled potential bulk electrolysis indicates that 94-99% of the nominal charge on different RAPs is accessible and the electrolysis products are stable upon cycling. The high concentration attainable (>2.0 M) for RAPs in common non-aqueous battery solvents, their electrochemical and chemical reversibility, and their hindered transport across porous separators make them attractive materials for non-aqueous redox flow batteries based on size-selectivity.

Dissecting the integrative antioxidant and redox systems in plant mitochondria. Effect of stress and S-nitrosylation.

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Juan José Lázaro

2013-11-01

Full Text Available Mitochondrial respiration provides the energy needed to drive metabolic and transport processes in cells. Mitochondria are a significant site of reactive oxygen species (ROS production in plant cells, and redox-system components obey fine regulation mechanisms that are essential in protecting the mitochondrial integrity. In addition to ROS, there are compelling indications that nitric oxide (NO. can be generated in this organelle by both reductive and oxidative pathways. ROS and reactive nitrogen species (RNS play a key role in signaling but they can also be deleterious via oxidation of macromolecules. The high production of ROS obligates mitochondria to be provided with a set of ROS scavenging mechanisms. The first line of mitochondrial antioxidants is composed of superoxide dismutase and the enzymes of the ascorbate-glutathione cycle, which are not only able to scavenge ROS but also to repair cell damage and possibly serve as redox sensors. The dithiol-disulfide exchanges form independent signaling nodes and act as antioxidant defense mechanisms as well as sensor proteins modulating redox signaling during development and stress adaptation. The presence of thioredoxin (Trx, peroxiredoxin (Prx and sulfiredoxin (Srx in the mitochondria has been recently reported. Cumulative results obtained from studies in salt stress models have demonstrated that these redox proteins play a significant role in the establishment of salt tolerance. The Trx/Prx/Srx system may be subjected to a fine regulated mechanism involving post-translational modifications, among which S-glutathionylation and S-nitrosylation seem to exhibit a critical role that is just beginning to be understood. This review summarizes our current knowledge in antioxidative systems in plant mitochondria, their interrelationships, mechanisms of compensation and some unresolved questions, with special focus on their response to abiotic stress.

Comparative study of the oxidation behavior of sulfur-containing amino acids and glutathione by electrochemistry-mass spectrometry in the presence and absence of cisplatin.

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Zabel, Robert; Weber, Günther

2016-02-01

Small sulfur-containing compounds are involved in several important biochemical processes, including-but not limited to-redox regulation and drug conjugation/detoxification. While methods for stable redox pairs of such compounds (thiols/disulfides) are available, analytical data on more labile and short-lived redox intermediates are scarce, due to highly challenging analytical requirements. In this study, we employ the direct combination of reagentless electrochemical oxidation and mass spectrometric (EC-MS) identification for monitoring oxidation reactions of cysteine, N-acetylcysteine, methionine, and glutathione under simulated physiological conditions (pH 7.4, 37 °C). For the first time, all theoretically expected redox intermediates-with only one exception-are detected simultaneously and in situ, including sulfenic, sulfinic, and sulfonic acids, disulfides, thiosulfinates, thiosulfonates, and sulfoxides. By monitoring the time/potential-dependent interconversion of sulfur species, mechanistic oxidation routes are confirmed and new reactions detected, e.g., sulfenamide formation due to reaction with ammonia from the buffer. Furthermore, our results demonstrate a highly significant impact of cisplatin on the redox reactivity of sulfur species. Namely, the amount of thiol oxidation to sulfonic acid via sulfenic and sulfinic acid intermediates is diminished for glutathione in the presence of cisplatin in favor of the disulfide formation, while for N-acetylcysteine the contrary applies. N-acetylcysteine is the only ligand which displays enhanced oxidation currents upon cisplatin addition, accompanied by increased levels of thiosulfinate and thiosulfonate species. This is traced back to thiol reactivity and highlights the important role of sulfenic acid intermediates, which may function as a switch between different oxidation routes.

Effects of microbial redox cycling of iron on cast iron pipe corrosion in drinking water distribution systems.

Science.gov (United States)

Wang, Haibo; Hu, Chun; Zhang, Lili; Li, Xiaoxiao; Zhang, Yu; Yang, Min

2014-11-15

Bacterial characteristics in corrosion products and their effect on the formation of dense corrosion scales on cast iron coupons were studied in drinking water, with sterile water acting as a reference. The corrosion process and corrosion scales were characterized by electrochemical and physico-chemical measurements. The results indicated that the corrosion was more rapidly inhibited and iron release was lower due to formation of more dense protective corrosion scales in drinking water than in sterile water. The microbial community and denitrifying functional genes were analyzed by pyrosequencing and quantitative polymerase chain reactions (qPCR), respectively. Principal component analysis (PCA) showed that the bacteria in corrosion products played an important role in the corrosion process in drinking water. Nitrate-reducing bacteria (NRB) Acidovorax and Hydrogenophaga enhanced iron corrosion before 6 days. After 20 days, the dominant bacteria became NRB Dechloromonas (40.08%) with the protective corrosion layer formation. The Dechloromonas exhibited the stronger corrosion inhibition by inducing the redox cycling of iron, to enhance the precipitation of iron oxides and formation of Fe3O4. Subsequently, other minor bacteria appeared in the corrosion scales, including iron-respiring bacteria and Rhizobium which captured iron by the produced siderophores, having a weaker corrosion-inhibition effect. Therefore, the microbially-driven redox cycling of iron with associated microbial capture of iron caused more compact corrosion scales formation and lower iron release. Copyright © 2014 Elsevier Ltd. All rights reserved.

Variation in risk indicators of cardiovascular disease during the menstrual cycle: an investigation of within-subject variations in glutathione peroxidase, haemostatic variables, lipids and lipoproteins in healthy young women

DEFF Research Database (Denmark)

Larsen, L F; Andersen, H R; Hansen, A B

1996-01-01

Variations in erythrocyte glutathione peroxidase activity, serum concentrations of lipids and lipoproteins and in blood coagulation and fibrinolysis during the menstrual cycle were studied in healthy young women. Blood samples were drawn twice a week for 9 weeks. A group of males was used...

A robust and versatile mass spectrometry platform for comprehensive assessment of the thiol redox metabolome

Directory of Open Access Journals (Sweden)

T.R. Sutton

2018-06-01

Full Text Available Several diseases are associated with perturbations in redox signaling and aberrant hydrogen sulfide metabolism, and numerous analytical methods exist for the measurement of the sulfur-containing species affected. However, uncertainty remains about their concentrations and speciation in cells/biofluids, perhaps in part due to differences in sample processing and detection principles. Using ultrahigh-performance liquid chromatography in combination with electrospray-ionization tandem mass spectrometry we here outline a specific and sensitive platform for the simultaneous measurement of 12 analytes, including total and free thiols, their disulfides and sulfide in complex biological matrices such as blood, saliva and urine. Total assay run time is < 10 min, enabling high-throughput analysis. Enhanced sensitivity and avoidance of artifactual thiol oxidation is achieved by taking advantage of the rapid reaction of sulfhydryl groups with N-ethylmaleimide. We optimized the analytical procedure for detection and separation conditions, linearity and precision including three stable isotope labelled standards. Its versatility for future more comprehensive coverage of the thiol redox metabolome was demonstrated by implementing additional analytes such as methanethiol, N-acetylcysteine, and coenzyme A. Apparent plasma sulfide concentrations were found to vary substantially with sample pretreatment and nature of the alkylating agent. In addition to protein binding in the form of mixed disulfides (S-thiolation a significant fraction of aminothiols and sulfide appears to be also non-covalently associated with proteins. Methodological accuracy was tested by comparing the plasma redox status of 10 healthy human volunteers to a well-established protocol optimized for reduced/oxidized glutathione. In a proof-of-principle study a deeper analysis of the thiol redox metabolome including free reduced/oxidized as well as bound thiols and sulfide was performed

New Approach in Translational Medicine: Effects of Electrolyzed Reduced Water (ERW on NF-κB/iNOS Pathway in U937 Cell Line under Altered Redox State

Directory of Open Access Journals (Sweden)

Sara Franceschelli

2016-09-01

Full Text Available It is known that increased levels of reactive oxygen species (ROS and reactive nitrogen species (RNS can exert harmful effects, altering the cellular redox state. Electrolyzed Reduced Water (ERW produced near the cathode during water electrolysis exhibits high pH, high concentration of dissolved hydrogen and an extremely negative redox potential. Several findings indicate that ERW had the ability of a scavenger free radical, which results from hydrogen molecules with a high reducing ability and may participate in the redox regulation of cellular function. We investigated the effect of ERW on H2O2-induced U937 damage by evaluating the modulation of redox cellular state. Western blotting and spectrophotometrical analysis showed that ERW inhibited oxidative stress by restoring the antioxidant capacity of superoxide dismutase, catalase and glutathione peroxidase. Consequently, ERW restores the ability of the glutathione reductase to supply the cell of an important endogenous antioxidant, such as GSH, reversing the inhibitory effect of H2O2 on redox balance of U937 cells. Therefore, this means a reduction of cytotoxicity induced by peroxynitrite via a downregulation of the NF-κB/iNOS pathway and could be used as an antioxidant for preventive and therapeutic application. In conclusion, ERW can protect the cellular redox balance, reducing the risk of several diseases with altered cellular homeostasis such as inflammation.

A redox-flow battery with an alloxazine-based organic electrolyte

Science.gov (United States)

Lin, Kaixiang; Gómez-Bombarelli, Rafael; Beh, Eugene S.; Tong, Liuchuan; Chen, Qing; Valle, Alvaro; Aspuru-Guzik, Alán; Aziz, Michael J.; Gordon, Roy G.

2016-09-01

Redox-flow batteries (RFBs) can store large amounts of electrical energy from variable sources, such as solar and wind. Recently, redox-active organic molecules in aqueous RFBs have drawn substantial attention due to their rapid kinetics and low membrane crossover rates. Drawing inspiration from nature, here we report a high-performance aqueous RFB utilizing an organic redox compound, alloxazine, which is a tautomer of the isoalloxazine backbone of vitamin B2. It can be synthesized in high yield at room temperature by single-step coupling of inexpensive o-phenylenediamine derivatives and alloxan. The highly alkaline-soluble alloxazine 7/8-carboxylic acid produces a RFB exhibiting open-circuit voltage approaching 1.2 V and current efficiency and capacity retention exceeding 99.7% and 99.98% per cycle, respectively. Theoretical studies indicate that structural modification of alloxazine with electron-donating groups should allow further increases in battery voltage. As an aza-aromatic molecule that undergoes reversible redox cycling in aqueous electrolyte, alloxazine represents a class of radical-free redox-active organics for use in large-scale energy storage.

Influence of Oxygen and Nitrate on Fe (Hydr)oxide Mineral Transformation and Soil Microbial Communities during Redox Cycling.

Science.gov (United States)

Mejia, Jacqueline; Roden, Eric E; Ginder-Vogel, Matthew

2016-04-05

Oscillations between reducing and oxidizing conditions are observed at the interface of anaerobic/oxic and anaerobic/anoxic environments, and are often stimulated by an alternating flux of electron donors (e.g., organic carbon) and electron acceptors (e.g., O2 and NO3(-)). In iron (Fe) rich soils and sediments, these oscillations may stimulate the growth of both Fe-reducing bacteria (FeRB) and Fe-oxidizing bacteria (FeOB), and their metabolism may induce cycling between Fe(II) and Fe(III), promoting the transformation of Fe (hydr)oxide minerals. Here, we examine the mineralogical evolution of lepidocrocite and ferrihydrite, and the adaptation of a natural microbial community to alternating Fe-reducing (anaerobic with addition of glucose) and Fe-oxidizing (with addition of nitrate or air) conditions. The growth of FeRB (e.g., Geobacter) is stimulated under anaerobic conditions in the presence of glucose. However, the abundance of these organisms depends on the availability of Fe(III) (hydr)oxides. Redox cycling with nitrate results in decreased Fe(II) oxidation thereby decreasing the availability of Fe(III) for FeRB. Additionally, magnetite is detected as the main product of both lepidocrocite and ferrihydrite reduction. In contrast, introduction of air results in increased Fe(II) oxidation, increasing the availability of Fe(III) and the abundance of Geobacter. In the lepidocrocite reactors, Fe(II) oxidation by dissolved O2 promotes the formation of ferrihydrite and lepidocrocite, whereas in the ferrihydrite reactors we observe a decrease in magnetite stoichiometry (e.g., oxidation). Understanding Fe (hydr)oxide transformation under environmentally relevant redox cycling conditions provides insight into nutrient availability and transport, contaminant mobility, and microbial metabolism in soils and sediments.

Arabidopsis GLUTATHIONE REDUCTASE1 plays a crucial role in leaf responses to intracellular hydrogen peroxide and in ensuring appropriate gene expression through both salicylic acid and jasmonic acid signaling pathways.

Science.gov (United States)

Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

2010-07-01

Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H(2)O(2)) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H(2)O(2) signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H(2)O(2). Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H(2)O(2)-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H(2)O(2) availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system.

Pattern-oriented Agent-based Monte Carlo simulation of Cellular Redox Environment

DEFF Research Database (Denmark)

Tang, Jiaowei; Holcombe, Mike; Boonen, Harrie C.M.

/CYSS) and mitochondrial redox couples. Evidence suggests that both intracellular and extracellular redox can affect overall cell redox state. How redox is communicated between extracellular and intracellular environments is still a matter of debate. Some researchers conclude based on experimental data...... cells. Biochimica Et Biophysica Acta-General Subjects, 2008. 1780(11): p. 1271-1290. 5. Jones, D.P., Redox sensing: orthogonal control in cell cycle and apoptosis signalling. J Intern Med, 2010. 268(5): p. 432-48. 6. Pogson, M., et al., Formal agent-based modelling of intracellular chemical interactions...

Catechol-chitosan redox capacitor for added amplification in electrochemical immunoanalysis.

Science.gov (United States)

Yan, Kun; Liu, Yi; Guan, Yongguang; Bhokisham, Narendranath; Tsao, Chen-Yu; Kim, Eunkyoung; Shi, Xiao-Wen; Wang, Qin; Bentley, William E; Payne, Gregory F

2018-05-22

Antibodies are common recognition elements for molecular detection but often the signals generated by their stoichiometric binding must be amplified to enhance sensitivity. Here, we report that an electrode coated with a catechol-chitosan redox capacitor can amplify the electrochemical signal generated from an alkaline phosphatase (AP) linked immunoassay. Specifically, the AP product p-aminophenol (PAP) undergoes redox-cycling in the redox capacitor to generate amplified oxidation currents. We estimate an 8-fold amplification associated with this redox-cycling in the capacitor (compared to detection by a bare electrode). Importantly, this capacitor-based amplification is generic and can be coupled to existing amplification approaches based on enzyme-linked catalysis or magnetic nanoparticle-based collection/concentration. Thus, the capacitor should enhance sensitivities in conventional immunoassays and also provide chemical to electrical signal transduction for emerging applications in molecular communication. Copyright © 2018 Elsevier B.V. All rights reserved.

An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients

International Nuclear Information System (INIS)

Parlanti, Eleonora; Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara; Zijno, Andrea; D’Errico, Mariarosaria; Simonelli, Valeria; Sanchez, Massimo; Fattibene, Paola; Falchi, Mario; Dogliotti, Eugenia

2015-01-01

Highlights: • Increased levels and different types of intracellular radical species as well as an altered glutathione redox state characterize XP-A human cells when compared to normal. • A more glycolytic metabolism and higher ATP levels are associated with alteration of mitochondrial morphology and response to mitochondrial toxicants when XPA is defective. • XP-A human cells show increased spontaneous micronuclei frequency, a hallmark of cancer risk. - Abstract: Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O_2_−· and H_2O_2 being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance ("1H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer

An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients

Energy Technology Data Exchange (ETDEWEB)

Parlanti, Eleonora [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Zijno, Andrea; D’Errico, Mariarosaria; Simonelli, Valeria [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Sanchez, Massimo [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Fattibene, Paola [Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Falchi, Mario [National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, Eugenia, E-mail: dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy)

2015-12-15

Highlights: • Increased levels and different types of intracellular radical species as well as an altered glutathione redox state characterize XP-A human cells when compared to normal. • A more glycolytic metabolism and higher ATP levels are associated with alteration of mitochondrial morphology and response to mitochondrial toxicants when XPA is defective. • XP-A human cells show increased spontaneous micronuclei frequency, a hallmark of cancer risk. - Abstract: Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O{sub 2−}· and H{sub 2}O{sub 2} being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance ({sup 1}H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a

The importance of kinetics and redox in the biogeochemical cycling of iron in the surface ocean.

Directory of Open Access Journals (Sweden)

Peter L. Croot

2012-06-01

Full Text Available It is now well established that Iron (Fe is a limiting element in many regions of the open ocean. Our current understanding of the key processes which control iron distribution in the open ocean have been largely based on thermodynamic measurements performed under the assumption of equilibrium conditions. Using this equilibrium approach, researchers have been able to detect and quantify organic complexing ligands in seawater and examine their role in increasing the overall solubility of iron. Our current knowledge about iron bioavailability to phytoplankton and bacteria is also based heavily on carefully controlled laboratory studies where it is assumed the chemical species are in equilibrium in line with the free ion association model (FIAM and/or its successor the biotic ligand model (BLM. Similarly most field work on Fe biogeochemistry generally consists of a single profile which is in essence a ‘snap-shot’ in time of the system under investigation. However it is well known that the surface ocean is an extremely dynamic environment and it is unlikely if thermodynamic equilibrium between all the iron species present is ever truly achieved. In sunlit waters this is mostly due to the daily passage of the sun across the sky leading to photoredox processes which alter Fe speciation by cycling between redox states and between inorganic and organic species. Episodic deposition events, are also important perturbations to iron cycling as they bring new iron to the system altering the equilibrium between species and phases. Over the last 20 years the mesoscale iron enrichment experiments (e.g. IronEx I /II, SOIREE, EisenEx, SOFeX, EIFeX, SAGE, SEEDS and SERIES I /II and the FeCycle (I/II experiments have provided the first insights into processes altering iron speciation and distribution which occur over temporal scales of days to weeks. Here we utilize new field data collected in the open ocean on the redox and complexation kinetics of iron in the

Ocean acidification affects redox-balance and ion-homeostasis in the life-cycle stages of Emiliania huxleyi.

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Sebastian D Rokitta

Full Text Available Ocean Acidification (OA has been shown to affect photosynthesis and calcification in the coccolithophore Emiliania huxleyi, a cosmopolitan calcifier that significantly contributes to the regulation of the biological carbon pumps. Its non-calcifying, haploid life-cycle stage was found to be relatively unaffected by OA with respect to biomass production. Deeper insights into physiological key processes and their dependence on environmental factors are lacking, but are required to understand and possibly estimate the dynamics of carbon cycling in present and future oceans. Therefore, calcifying diploid and non-calcifying haploid cells were acclimated to present and future CO(2 partial pressures (pCO(2; 38.5 Pa vs. 101.3 Pa CO(2 under low and high light (50 vs. 300 µmol photons m(-2 s(-1. Comparative microarray-based transcriptome profiling was used to screen for the underlying cellular processes and allowed to follow up interpretations derived from physiological data. In the diplont, the observed increases in biomass production under OA are likely caused by stimulated production of glycoconjugates and lipids. The observed lowered calcification under OA can be attributed to impaired signal-transduction and ion-transport. The haplont utilizes distinct genes and metabolic pathways, reflecting the stage-specific usage of certain portions of the genome. With respect to functionality and energy-dependence, however, the transcriptomic OA-responses resemble those of the diplont. In both life-cycle stages, OA affects the cellular redox-state as a master regulator and thereby causes a metabolic shift from oxidative towards reductive pathways, which involves a reconstellation of carbon flux networks within and across compartments. Whereas signal transduction and ion-homeostasis appear equally OA-sensitive under both light intensities, the effects on carbon metabolism and light physiology are clearly modulated by light availability. These interactive effects

Ocean acidification affects redox-balance and ion-homeostasis in the life-cycle stages of Emiliania huxleyi.

Science.gov (United States)

Rokitta, Sebastian D; John, Uwe; Rost, Björn

2012-01-01

Ocean Acidification (OA) has been shown to affect photosynthesis and calcification in the coccolithophore Emiliania huxleyi, a cosmopolitan calcifier that significantly contributes to the regulation of the biological carbon pumps. Its non-calcifying, haploid life-cycle stage was found to be relatively unaffected by OA with respect to biomass production. Deeper insights into physiological key processes and their dependence on environmental factors are lacking, but are required to understand and possibly estimate the dynamics of carbon cycling in present and future oceans. Therefore, calcifying diploid and non-calcifying haploid cells were acclimated to present and future CO(2) partial pressures (pCO(2); 38.5 Pa vs. 101.3 Pa CO(2)) under low and high light (50 vs. 300 µmol photons m(-2) s(-1)). Comparative microarray-based transcriptome profiling was used to screen for the underlying cellular processes and allowed to follow up interpretations derived from physiological data. In the diplont, the observed increases in biomass production under OA are likely caused by stimulated production of glycoconjugates and lipids. The observed lowered calcification under OA can be attributed to impaired signal-transduction and ion-transport. The haplont utilizes distinct genes and metabolic pathways, reflecting the stage-specific usage of certain portions of the genome. With respect to functionality and energy-dependence, however, the transcriptomic OA-responses resemble those of the diplont. In both life-cycle stages, OA affects the cellular redox-state as a master regulator and thereby causes a metabolic shift from oxidative towards reductive pathways, which involves a reconstellation of carbon flux networks within and across compartments. Whereas signal transduction and ion-homeostasis appear equally OA-sensitive under both light intensities, the effects on carbon metabolism and light physiology are clearly modulated by light availability. These interactive effects can be

Neutral Red and Ferroin as Reversible and Rapid Redox Materials for Redox Flow Batteries.

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Hong, Jeehoon; Kim, Ketack

2018-04-17

Neutral red and ferroin are used as redox indicators (RINs) in potentiometric titrations. The rapid response and reversibility that are prerequisites for RINs are also desirable properties for the active materials in redox flow batteries (RFBs). This study describes the electrochemical properties of ferroin and neutral red as a redox pair. The rapid reaction rates of the RINs allow a cell to run at a rate of 4 C with 89 % capacity retention after the 100 th  cycle. The diffusion coefficients, electrode reaction rates, and solubilities of the RINs were determined. The electron-transfer rate constants of ferroin and neutral red are 0.11 and 0.027 cm s -1 , respectively, which are greater than those of the components of all-vanadium and Zn/Br 2 cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Beyond the Fe-P-redox connection: preferential regeneration of phosphorus from organic matter as a key control on Baltic Sea nutrient cycles

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T. Jilbert

2011-06-01

Full Text Available Patterns of regeneration and burial of phosphorus (P in the Baltic Sea are strongly dependent on redox conditions. Redox varies spatially along water depth gradients and temporally in response to the seasonal cycle and multidecadal hydrographic variability. Alongside the well-documented link between iron oxyhydroxide dissolution and release of P from Baltic Sea sediments, we show that preferential remineralization of P with respect to carbon (C and nitrogen (N during degradation of organic matter plays a key role in determining the surplus of bioavailable P in the water column. Preferential remineralization of P takes place both in the water column and upper sediments and its rate is shown to be redox-dependent, increasing as reducing conditions become more severe at greater water-depth in the deep basins. Existing Redfield-based biogeochemical models of the Baltic may therefore underestimate the imbalance between N and P availability for primary production, and hence the vulnerability of the Baltic to sustained eutrophication via the fixation of atmospheric N. However, burial of organic P is also shown to increase during multidecadal intervals of expanded hypoxia, due to higher net burial rates of organic matter around the margins of the deep basins. Such intervals may be characterized by basin-scale acceleration of all fluxes within the P cycle, including productivity, regeneration and burial, sustained by the relative accessibility of the water column P pool beneath a shallow halocline.

Redox Fluctuations Increase the Contribution of Lignin to Soil Respiration

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Hall, S. J.; Silver, W. L.; Timokhin, V.; Hammel, K.

2014-12-01

Lignin mineralization represents a critical flux in the terrestrial carbon (C) cycle, yet little is known about mechanisms and environmental factors controlling lignin breakdown in mineral soils. Hypoxia has long been thought to suppress lignin decomposition, yet variation in oxygen (O2) availability in surface soils accompanying moisture fluctuations could potentially stimulate this process by generating reactive oxygen species via coupled biotic and abiotic iron (Fe) redox cycling. Here, we tested the impact of redox fluctuations on lignin breakdown in humid tropical forest soils during ten-week laboratory incubations. We used synthetic lignins labeled with 13C in either of two positions (aromatic methoxyl and propyl Cβ) to provide highly sensitive and specific measures of lignin mineralization not previously employed in soils. Four-day redox fluctuations increased the percent contribution of methoxyl C to soil respiration, and cumulative methoxyl C mineralization was equivalent under static aerobic and fluctuating redox conditions despite lower total C mineralization in the latter treatment. Contributions of the highly stable Cβ to mineralization were also equivalent in static aerobic and fluctuating redox treatments during periods of O2 exposure, and nearly doubled in the fluctuating treatment after normalizing to cumulative O2 exposure. Oxygen fluctuations drove substantial net Fe reduction and oxidation, implying that reactive oxygen species generated during abiotic Fe oxidation likely contributed to the elevated contribution of lignin to C mineralization. Iron redox cycling provides a mechanism for lignin breakdown in soils that experience conditions unfavorable for canonical lignin-degrading organisms, and provides a potential mechanism for lignin depletion in soil organic matter during late-stage decomposition. Thus, close couplings between soil moisture, redox fluctuations, and lignin breakdown provide potential a link between climate variability and

The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts.

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Jelena Markovic

2009-07-01

Full Text Available Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate.We have studied proliferation of 3T3 fibroblasts for a period of 5 days. Cells were treated with two well known depleting agents, diethyl maleate (DEM and buthionine sulfoximine (BSO, and the cellular and nuclear glutathione levels were assessed by analytical and confocal microscopic techniques, respectively. Both agents decreased total cellular glutathione although depletion by BSO was more sustained. However, the nuclear glutathione pool resisted depletion by BSO but not with DEM. Interestingly, cell proliferation was impaired by DEM, but not by BSO. Treating the cells simultaneously with DEM and with glutathione ethyl ester to restore intracellular GSH levels completely prevented the effects of DEM on cell proliferation.Our results demonstrate the importance of nuclear glutathione in the control of cell proliferation in 3T3 fibroblasts and suggest that a reduced nuclear environment is necessary for cells to progress in the cell cycle.

Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

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Muhammad, Faheem; Wang, Aifei; Qi, Wenxiu; Zhang, Shixing; Zhu, Guangshan

2014-01-01

Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

OpenAIRE

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the ro...

Redox cycles of vitamin E: Hydrolysis and ascorbic acid dependent reduction of 8a-(alkyldioxy)tocopherones

International Nuclear Information System (INIS)

Liebler, D.C.; Kaysen, K.L.; Kennedy, T.A.

1989-01-01

Oxidation of the biological antioxidant α-tocopherol (vitamin E; TH) by peroxyl radicals yields 8a-(alkyldioxy)tocopherones, which either may hydrolyze to α-tocopheryl quinone (TQ) or may be reduced by ascorbic acid to regenerate TH. To define the chemistry of this putative two-electron TH redox cycle, we studied the hydrolysis and reduction of 8a-[(2,4-dimethyl-1-nitrilopent-2-yl)dioxyl]tocopherone (1) in acetonitrile/buffer mixtures and in phospholipid liposomes. TQ formation in acetonitrile/buffer mixtures, which was monitored spectrophotometrically, declined with increasing pH and could not be detected above pH 4. The rate of TQ formation from 1 first increased with time and then decreased in a first-order terminal phase. Rearrangement of 8a-hydroxy-α-tocopherone (2) to TQ displayed first-order kinetics identical with the terminal phase for TQ formation from 1. Both rate constants increased with decreasing pH. Hydrolysis of 1 in acetonitrile/H 2 18 O yielded [ 18 O]TQ. These observations suggest that 1 loses the 8a-(alkyldioxy) moiety to produce the tocopherone cation (T + ), which hydrolyzes to 2, the TQ-forming intermediate. Incubation of either 1 or 2 with ascorbic acid in acetonitrile/buffer yielded TH. Reduction of both 1 and 2 decreased with increasing pH. In phosphatidylcholine liposomes at pH 7, approximately 10% of the T + generated from 1 was reduced to TH by 5 mM ascorbic acid. The results collectively demonstrate that T + is the ascorbic acid reducible intermediate in a two-electron TH redox cycle, a process that probably would require biocatalysis to proceed in biological membranes

Ascorbate oxidase-dependent changes in the redox state of the apoplast modulate gene transcript accumulation leading to modified hormone signaling and orchestration of defense processes in tobacco.

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Pignocchi, Cristina; Kiddle, Guy; Hernández, Iker; Foster, Simon J; Asensi, Amparo; Taybi, Tahar; Barnes, Jeremy; Foyer, Christine H

2006-06-01

The role of the redox state of the apoplast in hormone responses, signaling cascades, and gene expression was studied in transgenic tobacco (Nicotiana tabacum) plants with modified cell wall-localized ascorbate oxidase (AO). High AO activity specifically decreased the ascorbic acid (AA) content of the apoplast and altered plant growth responses triggered by hormones. Auxin stimulated shoot growth only when the apoplastic AA pool was reduced in wild-type or AO antisense lines. Oxidation of apoplastic AA in AO sense lines was associated with loss of the auxin response, higher mitogen-activated protein kinase activities, and susceptibility to a virulent strain of the pathogen Pseudomonas syringae. The total leaf glutathione pool, the ratio of reduced glutathione to glutathione disulfide, and glutathione reductase activities were similar in the leaves of all lines. However, AO sense leaves exhibited significantly lower dehydroascorbate reductase and ascorbate peroxidase activities than wild-type and antisense leaves. The abundance of mRNAs encoding antioxidant enzymes was similar in all lines. However, the day/night rhythms in the abundance of transcripts encoding the three catalase isoforms were changed in response to the AA content of the apoplast. Other transcripts influenced by AO included photorespiratory genes and a plasma membrane Ca(2+) channel-associated gene. We conclude that the redox state of the apoplast modulates plant growth and defense responses by regulating signal transduction cascades and gene expression patterns. Hence, AO activity, which modulates the redox state of the apoplastic AA pool, strongly influences the responses of plant cells to external and internal stimuli.

Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver.

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Sadi, Gökhan; Bozan, Davut; Yildiz, Huseyin Bekir

2014-08-01

Resveratrol is a strong antioxidant that exhibits blood glucose-lowering effects, which might contribute to its usefulness in preventing complications associated with diabetes. The present study aimed to investigate resveratrol effects on catalase (CAT) and glutathione peroxidase (GPx) gene and protein expression, their phosphorylation states and activities in rat liver of STZ-induced diabetes. Diabetes increased the levels of total protein phosphorylation and p-CAT, while mRNA expression, protein levels, and activity were reduced. Although diabetes induced transcriptional repression over GPx, it did not affect the protein levels and activity. When resveratrol was administered to diabetic rats, an increase in activity was associated with an increase in p-GPx levels. Decrease in Sirtuin1 (SIRT1) and nuclear factor erythroid 2-related factor (Nrf2) and increase in nuclear factor kappa B (NFκB) gene expression in diabetes were associated with a decrease in CAT and GPx mRNA expression. A possible compensatory mechanism for reduced gene expression of antioxidant enzymes is proved to be nuclear translocation of redox-sensitive Nrf2 and NFκB in diabetes which is confirmed by the increase in nuclear and decrease in cytoplasmic protein levels of Nrf2 and NFκB. Taken together, these findings revealed that an increase in the oxidized state in diabetes intricately modified the cellular phosphorylation status and regulation of antioxidant enzymes. Gene regulation of antioxidant enzymes was accompanied by nuclear translocation of Nrf2 and NFκB. Resveratrol administration also activated a coordinated cytoprotective response against diabetes-induced changes in liver tissues.

Cucurbita ficifolia Bouché (Cucurbitaceae) and D-chiro-inositol modulate the redox state and inflammation in 3T3-L1 adipocytes.

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Fortis-Barrera, Ángeles; Alarcón-Aguilar, Francisco Javier; Banderas-Dorantes, Tania; Díaz-Flores, Margarita; Román-Ramos, Rubén; Cruz, Miguel; García-Macedo, Rebeca

2013-10-01

Cucurbita ficifolia (characterised by its D chiro inositol (DCI) content) and of synthetic DCI on the redox state, mRNA expression and secretions of proinflammatory cytokines. Additionally, we evaluated the insulin-mimetic action of both treatments by assessing protein kinase B (PKB) activation in 3T3-L1 adipocytes. Adipocytes were treated with C. ficifolia and synthetic DCI. The redox state was determined by spectrophotometry as changes in the reduced glutathione/oxidised glutathione (GSH/GSSG) ratio, glutathione peroxidase and glutathione reductase activities; H2 O2 levels were measured by flow cytometry. The mRNA expression and the protein level of cytokines were determinate by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activation of PKB activation was detected by Western blot. C. ficifolia extract and synthetic DCI reduced oxidative stress by decreased H2 O2 levels, increased glutathione peroxidase activity and changes in the GSH/GSSG ratio. Furthermore, DCI decreased the mRNA expression and secretion of tumour necrosis factor-α, interleukin 6 (IL-6) and resistin, while C. ficifolia reduced protein levels of resistin and increased IL-6 levels. Only DCI demonstrated insulin-mimetic action. The antioxidant and anti-inflammatory effects of C. ficifolia extract can be explained in part by its DCI content, which modulates the GSH/GSSG ratio and contributes to a reduced proinflammatory state. C. ficifolia and DCI treatments may reduce the disturbances caused by oxidative stress. Additionally, DCI may improve insulin sensitivity through its insulin-mimetic effects. © 2013 Royal Pharmaceutical Society.

Cytotoxicity from coupled redox cycling of autoxidizing xenobiotics and metals: a selective critical review and commentary on work-in-progress

Energy Technology Data Exchange (ETDEWEB)

Borg, D C; Schaich, K M

1984-01-01

A comprehensive reaction schema for oxidative cytotoxicity is presented, integrating known chemical mechanisms of oxygen radical reactions and observed pathophysiology. The key features of the schema are the coupling of (1) redox cycling of autoxidizable substrates to form the equilibrium pair of superoxide anion (O/sub 2//sup -/)/and its conjugate acid, perhydroxyl radical (HO/sub 2/.); (2) hydrogen peroxide (H/sub 2/O/sub 2/) generation via O/sub 2//sup -/ dimutation; (3) catalytic redox cycling of metals reducing H/sub 2/O/sub 2/ to reactive hydroxyl radicals (OH.); (4) direct reaction of OH. with target molecules, including critical cell macromolecules and polyunsaturated lipids in membranes; (5) transfer of oxidative potential from initial to distant sites via H/sub 2/O/sub 2/ and O/sub 2/-/HO/sub 2/ diffusion, lipid free radical chain peroxidations in membranes, and migration of non-radical lipid oxidation products; and (6) cytotoxic damage at those distant sites mediated by reaction of lipid radical species and other lipid oxidation products with critical target molecules (proteins, DNA, etc.). Although there is a broad consensus of agreement within the cognizant research community concerning many aspects of this schema, there exists considerable controversy and/or misconception about several important issues. Critical analyses of four presently controversial points are presented.

Redox imbalance and mitochondrial abnormalities in the diabetic lung.

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Wu, Jinzi; Jin, Zhen; Yan, Liang-Jun

2017-04-01

Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD + redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung. Using STZ induced diabetes in rat as a model, we measured redox-imbalance related parameters including aldose reductase activity, level of poly ADP ribose polymerase (PAPR-1), NAD + content, NADPH content, reduced form of glutathione (GSH), and glucose 6-phophate dehydrogenase (G6PD) activity. For assessment of mitochondrial abnormalities in the diabetic lung, we measured the activities of mitochondrial electron transport chain complexes I to IV and complex V as well as dihydrolipoamide dehydrogenase (DLDH) content and activity. We also measured the protein content of NAD + dependent enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Our results demonstrate that NADH/NAD + redox imbalance occurs in the diabetic lung. This redox imbalance upregulates the activities of complexes I to IV, but not complex V; and this upregulation is likely the source of increased mitochondrial ROS production, oxidative stress, and cell death in the diabetic lung. These results, together with the findings that the protein contents of DLDH, sirt3, and NQO1 all are decreased in the diabetic lung, demonstrate that redox imbalance, mitochondrial abnormality, and oxidative stress contribute to lung injury in diabetes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Redox-mediated bypass of restriction point via skipping of G1pm

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Greene James J

2006-07-01

Full Text Available Abstract Background It is well known that cancer cells bypass the restriction point, R, and undergo uncontrolled cell proliferation. Hypothesis and evidence We suggest here that fibrosarcoma cells enter G1ps directly from M, skipping G1pm, hence bypassing R, in response to redox modulation. Evidence is presented from the published literature that demonstrate a shortening of the cycle period of transformed fibroblasts (SV-3T3 compared to the nontransformed 3T3 fibroblasts, corresponding to the duration of G1pm in the 3T3 fibroblasts. Evidence is also presented that demonstrate that redox modulation can induce the CUA-4 fibroblasts to bypass R, resulting in a cycle period closely corresponding to the cycle period of fibrosarcoma cells (HT1080. Conclusion The evidence supports our hypothesis that a low internal redox potential can cause fibrosarcoma cells to skip the G1pm phase of the cell cycle.

Effect of the Linker in Terephthalate-Functionalized Conducting Redox Polymers

International Nuclear Information System (INIS)

Yang, Li; Huang, Xiao; Gogoll, Adolf; Strømme, Maria; Sjödin, Martin

2016-01-01

The combination of high capacity redox active pendent groups and conducting polymers, realized in conducting redox polymers (CRPs), provides materials with high charge storage capacity that are electronically conducting which makes CRPs attractive for electrical energy storage applications. In this report, six polythiophene and poly(3,4-ethylenedioxythiophene)(PEDOT)-based CRPs with a diethyl terephthalate unit covalently bound to the polymer chain by various linkers have been synthesized and characterized electrochemically. The effects of the choice of polymer backbone and of the nature of the link on the electrochemistry, and in particular the cycling stability of these polymers, are discussed. All CRPs show both the doping of the polymer backbone as well as the redox behavior of the pendent groups and the redox potential of the pendent groups in the CRPs is close to that of corresponding monomer, indicating insignificant interaction between the pendant and the polymer backbone. While all CRPs show various degrees of charge decay upon electrochemical redox conversion, the PEDOT-based CRPs show significantly improved stability compared to the polythiophene counterparts. Moreover, we show that by the right choice of link the cycling stability of diethyl terephthalate substituted PEDOT-based CRPs can be significantly improved.

Glutathione and Mitochondria

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Vicent eRibas

2014-07-01

Full Text Available Glutathione (GSH is the main nonprotein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease and Alzheimer’s disease.

Systemic induction of NO-, redox- and cGMP signalling in the pumpkin extrafascicular phloem upon local leaf wounding

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Frank eGaupels

2016-02-01

Full Text Available Cucurbits developed the unique extrafascicular phloem (EFP as a defensive structure against herbivorous animals. Mechanical leaf injury was previously shown to induce a systemic wound response in the EFP of pumpkin (Cucurbita maxima. Here, we demonstrate that the phloem antioxidant system and protein modifications by NO are strongly regulated during this process. Activities of the central antioxidant enzymes dehydroascorbate reductase, glutathione reductase and ascorbate reductase were rapidly down-regulated at 30 min with a second minimum at 24 h after wounding. As a consequence levels of total ascorbate and glutathione also decreased with similar bi-phasic kinetics. These results hint towards a wound-induced shift in the redox status of the EFP. Nitric oxide (NO is another important player in stress-induced redox signalling in plants. Therefore, we analysed NO-dependent protein modifications in the EFP. Six to 48 h after leaf damage total S-nitrosothiol content and protein S-nitrosylation were clearly reduced, which was contrasted by a pronounced increase in protein tyrosine nitration. Collectively, these findings suggest that NO-dependent S-nitrosylation turned into peroxynitrite-mediated protein nitration upon a stress-induced redox shift probably involving the accumulation of reactive oxygen species within the EFP. Using the biotin switch assay and anti-nitrotyrosine antibodies we identified 9 candidate S-nitrosylated and 6 candidate tyrosine-nitrated phloem proteins. The wound-responsive Phloem Protein 16-1 (PP16-1 and Cyclophilin 18 (CYP18 as well as the 26.5 kD isoform of Phloem Protein 2 (PP2 were amenable to both NO modifications and could represent important redox-sensors within the cucurbit EFP. We also found that leaf injury triggered the systemic accumulation of cyclic guanosine monophosphate (cGMP in the EFP and discuss the possible function of this second messenger in systemic NO and redox signalling within the EFP.

Cooperative functions of manganese and thiol redox system against oxidative stress in human spermatozoa

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Amrit Kaur Bansal

2009-01-01

Full Text Available Aims: In this study, the effects of 0.1 mM Mn 2+ on thiol components (total thiols [TSH], glutathione reduced [GSH], glutathione oxidized [GSSG] and redox ratio [GSH/ GSSG] have been determined in human spermatozoa. Settings and Design: The subjects of the study were healthy males having more than 75% motility and 80 x 10 6 sperms/mL. Materials and Methods: Fresh semen was suspended in phosphate-buffered saline (PBS (pH 7.2 and this suspension was divided into eight equal fractions. All fractions, control (containing PBS and experimental (treated/untreated with [ferrous ascorbate, FeAA - 200 FeSO 4 μM, 1000 μM ascorbic acid, nicotine (0.5 mM and FeAA + nicotine], supplemented/unsupplemented with Mn 2+ [0.1 mM], were incubated for 2 h at 378C. These fractions were assessed for determining the thiol components. Statistical Analysis: The data were statistically analyzed by Students " t" test. Results and Conclusions: Ferrous ascorbate, nicotine and ferrous ascorbate + nicotine induced oxidative stress and decreased GSH and redox ratio (GSH/GSSG ratio but increased the TSH and GSSG levels. Mn 2+ supplementation improved TSH, GSH and redox ratio (GSH/GSSG but decreased the GSSG level under normal and oxidative stress conditions. Thiol groups serve as defense mechanisms of sperm cells to fight against oxidative stress induced by stress inducers such as ferrous ascorbate, nicotine and their combination (ferrous ascorbate + nicotine. In addition, Mn 2+ supplementation maintains the thiol level by reducing oxidative stress.

Transcriptional profile of genes involved in ascorbate glutathione cycle in senescing leaves for an early senescence leaf (esl) rice mutant.

Science.gov (United States)

Li, Zhaowei; Su, Da; Lei, Bingting; Wang, Fubiao; Geng, Wei; Pan, Gang; Cheng, Fangmin

2015-03-15

To clarify the complex relationship between ascorbate-glutathione (AsA-GSH) cycle and H2O2-induced leaf senescence, the genotype-dependent difference in some senescence-related physiological parameters and the transcript levels and the temporal patterns of genes involved in the AsA-GSH cycle during leaf senescence were investigated using two rice genotypes, namely, the early senescence leaf (esl) mutant and its wild type. Meanwhile, the triggering effect of exogenous H2O2 on the expression of OsAPX genes was examined using detached leaves. The results showed that the esl mutant had higher H2O2 level than its wild type at the initial stage of leaf senescence. At transcriptional level, the association of expression of various genes involved in the AsA-GSH cycle with leaf senescence was isoform dependent. For OsAPXs, the transcripts of two cytosolic OsAPX genes (OsAPX1 and OsAPX2), thylakoid-bound OsAPX8, chloroplastic OsAPX7 and peroxisomal OsAPX4 exhibited remarkable genotype-dependent variation in their expression levels and temporal patterns during leaf senescence, there were significantly increasing transcripts of OsAXP1 and OsAPX7, severely repressed transcripts of OsAPX4 and OsAPX8 for the esl rice at the initial leaf senescence. In contrast, the repressing transcript of OsAPX8 was highly sensitive to the increasing H2O2 level in the senescing rice leaves, while higher H2O2 concentration resulted in the enhancing transcripts of two cytosolic OsAPX genes, OsAPX7 transcript was greatly variable with different H2O2 concentrations and incubating duration, suggesting that the different OsAPXs isoforms played a complementary role in perceiving and scavenging H2O2 accumulation at various H2O2 concentrations during leaf senescence. Higher H2O2 level, increased AsA level, higher activities of APX and glutathione reductase (GR), and relatively stable GSH content during the entire sampling period in the leaves of esl mutant implied that a close interrelationship existed

A biomimetic redox flow battery based on flavin mononucleotide.

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Orita, Akihiro; Verde, Michael G; Sakai, Masanori; Meng, Ying Shirley

2016-10-21

The versatility in design of redox flow batteries makes them apt to efficiently store energy in large-scale applications at low cost. The discovery of inexpensive organic electroactive materials for use in aqueous flow battery electrolytes is highly attractive, but is thus far limited. Here we report on a flow battery using an aqueous electrolyte based on the sodium salt of flavin mononucleotide. Flavins are highly versatile electroactive molecules, which catalyse a multitude of redox reactions in biological systems. We use nicotinamide (vitamin B3) as a hydrotropic agent to enhance the water solubility of flavin mononucleotide. A redox flow battery using flavin mononucleotide negative and ferrocyanide positive electrolytes in strong base shows stable cycling performance, with over 99% capacity retention over the course of 100 cycles. We hypothesize that this is enabled due to the oxidized and reduced forms of FMN-Na being stabilized by resonance structures.

A biomimetic redox flow battery based on flavin mononucleotide

Science.gov (United States)

Orita, Akihiro; Verde, Michael G.; Sakai, Masanori; Meng, Ying Shirley

2016-10-01

The versatility in design of redox flow batteries makes them apt to efficiently store energy in large-scale applications at low cost. The discovery of inexpensive organic electroactive materials for use in aqueous flow battery electrolytes is highly attractive, but is thus far limited. Here we report on a flow battery using an aqueous electrolyte based on the sodium salt of flavin mononucleotide. Flavins are highly versatile electroactive molecules, which catalyse a multitude of redox reactions in biological systems. We use nicotinamide (vitamin B3) as a hydrotropic agent to enhance the water solubility of flavin mononucleotide. A redox flow battery using flavin mononucleotide negative and ferrocyanide positive electrolytes in strong base shows stable cycling performance, with over 99% capacity retention over the course of 100 cycles. We hypothesize that this is enabled due to the oxidized and reduced forms of FMN-Na being stabilized by resonance structures.

Carbon Redox-Polymer-Gel Hybrid Supercapacitors

Science.gov (United States)

Vlad, A.; Singh, N.; Melinte, S.; Gohy, J.-F.; Ajayan, P.M.

2016-01-01

Energy storage devices that provide high specific power without compromising on specific energy are highly desirable for many electric-powered applications. Here, we demonstrate that polymer organic radical gel materials support fast bulk-redox charge storage, commensurate to surface double layer ion exchange at carbon electrodes. When integrated with a carbon-based electrical double layer capacitor, nearly ideal electrode properties such as high electrical and ionic conductivity, fast bulk redox and surface charge storage as well as excellent cycling stability are attained. Such hybrid carbon redox-polymer-gel electrodes support unprecedented discharge rate of 1,000C with 50% of the nominal capacity delivered in less than 2 seconds. Devices made with such electrodes hold the potential for battery-scale energy storage while attaining supercapacitor-like power performances. PMID:26917470

Effect of inhaled N-acetylcysteine monotherapy on lung function and redox balance in idiopathic pulmonary fibrosis.

Science.gov (United States)

Muramatsu, Yoko; Sugino, Keishi; Ishida, Fumiaki; Tatebe, Junko; Morita, Toshisuke; Homma, Sakae

2016-05-01

An oxidant-antioxidant imbalance is considered to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Therefore, administration of antioxidants, such as N-acetylcysteine (NAC), may represent a potential treatment option for IPF patients. The aim of this study was to evaluate the effect of inhaled NAC monotherapy on lung function and redox balance in patients with IPF. A retrospective observational study was done, involving 22 patients with untreated early IPF (19 men; mean [±S.D.] age, 71.8 [±6.3]y). At baseline and at 6 and 12 months after initiating inhaled NAC monotherapy, we assessed forced vital capacity (FVC) and measured the levels of total glutathione, oxidized glutathione (GSSG), and the ratio of reduced to oxidized glutathione in whole blood (hereafter referred to as the ratio), and of 8-hydroxy-2'-deoxyguanosine in urine. To evaluate response to treatment, we defined disease progression as a decrease in FVC of ≥5% from baseline and stable disease as a decrease in FVC of <5%, over a period of 6 months. Change in FVC in the stable group at 6 and 12 months were 95±170mL and -70±120mL, while those in the progressive group at 6 and 12 months were -210±80mL, -320±350mL, respectively. The serial mean change in GSSG from baseline decreased as the ratio of reduced to oxidized glutathione increased in patients with stable disease, while it increased as this ratio decreased in patients with progressive disease. Receiver operating characteristic curve analysis revealed that a baseline GSSG level of ≥1.579μM was optimal for identifying treatment responders. Inhaled NAC monotherapy was associated with improved redox imbalance in patients with early IPF. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Albumin nanoparticles for glutathione-responsive release of cisplatin: New opportunities for medulloblastoma.

Science.gov (United States)

Catanzaro, Giuseppina; Curcio, Manuela; Cirillo, Giuseppe; Spizzirri, Umile Gianfranco; Besharat, Zein Mersini; Abballe, Luana; Vacca, Alessandra; Iemma, Francesca; Picci, Nevio; Ferretti, Elisabetta

2017-01-30

Redox-responsive nanoparticles were synthesized by desolvation of bovine serum albumin followed by disulfide-bond crosslinking with N, N'-Bis (acryloyl) cystamine. Dynamic light scattering and transmission electron microscopy studies revealed spherical nanoparticles (mean diameter: 83nm, polydispersity index: 0.3) that were glutathione-responsive. Confocal microscopy revealed rapid, efficient internalization of the nanoparticles by Daoy medulloblastoma cells and healthy controls (HaCaT keratinocytes). Cisplatin-loaded nanoparticles with drug:carrier ratios of 5%, 10%, and 20% were tested in both cell lines. The formulation with the highest drug:carrier ratio reduced Daoy and HaCaT cell viability with IC 50 values of 6.19 and 11.17μgmL -1 , respectively. The differential cytotoxicity reflects the cancer cells' higher glutathione content, which triggers more extensive disruption of the disulfide bond-mediated intra-particle cross-links, decreasing particle stability and increasing their cisplatin release. These findings support continuing efforts to improve the safety and efficacy of antineoplastic drug therapy for pediatric brain tumors using selective nanoparticle-based drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Delineation of the Pasteurellaceae-specific GbpA-family of glutathione-binding proteins

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Vergauwen Bjorn

2011-11-01

Full Text Available Abstract Background The Gram-negative bacterium Haemophilus influenzae is a glutathione auxotroph and acquires the redox-active tripeptide by import. The dedicated glutathione transporter belongs to the ATP-binding cassette (ABC-transporter superfamily and displays more than 60% overall sequence identity with the well-studied dipeptide (Dpp permease of Escherichia coli. The solute binding protein (SBP that mediates glutathione transport in H. influenzae is a lipoprotein termed GbpA and is 54% identical to E. coli DppA, a well-studied member of family 5 SBP's. The discovery linking GbpA to glutathione import came rather unexpectedly as this import-priming SBP was previously annotated as a heme-binding protein (HbpA, and was thought to mediate heme acquisition. Nonetheless, although many SBP's have been implicated in more than one function, a prominent physiological role for GbpA and its partner permease in heme acquisition appears to be very unlikely. Here, we sought to characterize five representative GbpA homologs in an effort to delineate the novel GbpA-family of glutathione-specific family 5 SBPs and to further clarify their functional role in terms of ligand preferences. Results Lipoprotein and non-lipoprotein GbpA homologs were expressed in soluble form and substrate specificity was evaluated via a number of ligand binding assays. A physiologically insignificant affinity for hemin was observed for all five GbpA homologous test proteins. Three out of five test proteins were found to bind glutathione and some of its physiologically relevant derivatives with low- or submicromolar affinity. None of the tested SBP family 5 allocrites interacted with the remaining two GbpA test proteins. Structure-based sequence alignments and phylogenetic analysis show that the two binding-inert GbpA homologs clearly form a separate phylogenetic cluster. To elucidate a structure-function rationale for this phylogenetic differentiation, we determined the crystal

Glutathione peroxidase activity in the selenium-treated alga Scenedesmus quadricauda

Czech Academy of Sciences Publication Activity Database

Vítová, Milada; Bišová, Kateřina; Hlavová, Monika; Zachleder, Vilém; Rucki, M.; Čížková, Mária

2011-01-01

Roč. 102, 1-2 (2011), s. 87-94 ISSN 0166-445X R&D Projects: GA ČR GA525/09/0102 Institutional research plan: CEZ:AV0Z50200510 Keywords : Cell cycle * Enzyme activity * Glutathione peroxidase Subject RIV: EE - Microbiology, Virology Impact factor: 3.761, year: 2011

Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees.

Science.gov (United States)

González, Alberto; Moenne, Fabiola; Gómez, Melissa; Sáez, Claudio A; Contreras, Rodrigo A; Moenne, Alejandra

2014-01-01

In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control), with OC kappa at 1 mg mL(-1), or treated with inhibitors of NAD(P)H, ascorbate (ASC), and glutathione (GSH) syntheses and thioredoxin reductase (TRR) activity, CHS-828, lycorine, buthionine sulfoximine (BSO), and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX) activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS), adenosine 5'-phosphosulfate reductase (APR), involved in C, N, and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH, and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH, and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle, and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC, and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses, and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism, and growth in Eucalyptus trees.

Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees

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Alberto eGonzález

2014-10-01

Full Text Available In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control, with OC kappa at 1 mg mL-1, or treated with inhibitors of NAD(PH, ascorbate (ASC and glutathione (GSH syntheses and thioredoxin reductase (TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS, adenosine 5´-phosphosulfate reductase (APR, involved in C, N and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism and growth in Eucalyptus trees.

Both the concentration and redox state of glutathione and ascorbate influence the sensitivity of arabidopsis to cadmium

NARCIS (Netherlands)

Jozefczak, M.; Bohler, S.; Schat, H.; Horemans, N.; Guisez, Y.; Remans, T.; Vangronsveld, J.; Cuypers, A.

2015-01-01

Background and Aims Cadmium (Cd) is a non-essential trace element that elicits oxidative stress. Plants respond to Cd toxicity via increasing their Cd-chelating and antioxidative capacities. They predominantly chelate Cd via glutathione (GSH) and phytochelatins (PCs), while antioxidative defence is

Radical Compatibility with Nonaqueous Electrolytes and Its Impact on an All-Organic Redox Flow Battery.

Science.gov (United States)

Wei, Xiaoliang; Xu, Wu; Huang, Jinhua; Zhang, Lu; Walter, Eric; Lawrence, Chad; Vijayakumar, M; Henderson, Wesley A; Liu, Tianbiao; Cosimbescu, Lelia; Li, Bin; Sprenkle, Vincent; Wang, Wei

2015-07-20

Nonaqueous redox flow batteries hold the promise of achieving higher energy density because of the broader voltage window than aqueous systems, but their current performance is limited by low redox material concentration, cell efficiency, cycling stability, and current density. We report a new nonaqueous all-organic flow battery based on high concentrations of redox materials, which shows significant, comprehensive improvement in flow battery performance. A mechanistic electron spin resonance study reveals that the choice of supporting electrolytes greatly affects the chemical stability of the charged radical species especially the negative side radical anion, which dominates the cycling stability of these flow cells. This finding not only increases our fundamental understanding of performance degradation in flow batteries using radical-based redox species, but also offers insights toward rational electrolyte optimization for improving the cycling stability of these flow batteries. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Redox oscillation impact on natural and engineered biogeochemical systems: chemical resilience and implications for contaminant mobility

Energy Technology Data Exchange (ETDEWEB)

Charlet, Laurent [ISTerre, University of Grenoble, B.P. 53X, 38041 Grenoble (France); Institut Universitaire de France, Paris (France); Markelova, Ekaterina [ISTerre, University of Grenoble, B.P. 53X, 38041 Grenoble (France); Department of Earth and Environmental Sciences, University of Waterloo, Waterloo, ON N2L3G1 4 (Canada); Parsons, Chris; Couture, Raoul-Marie [Department of Earth and Environmental Sciences, University of Waterloo, Waterloo, ON N2L3G1 4 (Canada); Made, Benoit [Andra / DRD-TR, Direction Recherche et Developpement, 1-7 rue Jean Monnet, 92298 Chatenay-Malabry cedex (France)

2013-07-01

Many geochemical systems fluctuate regularly from oxic to anoxic conditions (flooded soils and nuclear waste surface repositories, for instance). In these conditions many inorganic contaminants including Sb, Se, Cr, As, and U are highly sensitive to changes in redox conditions. These oscillations may result in changes to their speciation, toxicity, and mobility. We demonstrate through the combination of redox-stat batch-reactor experiments that periodic and cumulative changes to matrix mineralogy, contaminant speciation, and mineral surface properties occur following periodic cycles of reduction and oxidation. These changes result in both short-term (intra-cycle) and long-term (inter-cycle) changes to K{sub d} values for a range of redox sensitive contaminants. These results demonstrate that naturally occurring redox oscillations may result in long-term immobilization of contaminants in the solid phase in addition to short-term variations in mobility. (authors)

Novel interaction of diethyldithiocarbamate with the glutathione/glutathione peroxidase system

International Nuclear Information System (INIS)

Kumar, K.S.; Sancho, A.M.; Weiss, J.F.

1986-01-01

Diethyldithiocarbamate (DDC) exhibits a variety of pharmacologic activities, including both radioprotective and sensitizing properties. Since the glutathione/glutathione peroxidase system may be a significant factor in determining radiation sensitivity, the potential mechanisms of action of DDC in relation to this system were examined in vitro. The interaction of DDC with reduced glutathione (GSH) was tested using a simple system based on the reduction of cytochrome c. When DDC (0.005 mM) was incubated with GSH (0.5 mM), the reduction of cytochrome c was eightfold greater than that expected from an additive effect of DDC and GSH. GSH could be replaced by oxidized glutathione and glutathione reductase. Cytochrome c reduced by DDC was oxidized by mitochondria. The interaction of DDC with both the hexosemonophosphate shunt pathway and the mitochondrial respiratory chain suggests the possibility of linking these two pathways through DDC. Oxidation of DDC by peroxide and reversal by GSH indicated that the drug can engage in a cyclic reaction with peroxide and GSH. This was confirmed when DDC was used in the assay system for glutathione peroxidase (GSHPx) without GSHPx. DDC at a concentration of 0.25 mM was more active than 0.01 unit of pure GSHPx in eliminating peroxide, and much more active than the other sulfhydryl compounds tested. These studies indicate that DDC can supplement GSHPx activity or substitute for it in detoxifying peroxides, and suggests a unique role in the chemical modification of radiation sensitivity

Age-Related Responses in Circulating Markers of Redox Status in Healthy Adolescents and Adults during the Course of a Training Macrocycle

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Athanasios Zalavras

2015-01-01

Full Text Available Redox status changes during an annual training cycle in young and adult track and field athletes and possible differences between the two age groups were assessed. Forty-six individuals (24 children and 22 adults were assigned to four groups: trained adolescents, (TAD, N=13, untrained adolescents (UAD, N=11, trained adults (TA, N=12, and untrained adults (UA, N=10. Aerobic capacity and redox status related variables [total antioxidant capacity (TAC, glutathione (GSH, catalase activity, TBARS, protein carbonyls (PC, uric acid, and bilirubin] were assessed at rest and in response to a time-trial bout before training, at mid- and posttraining. TAC, catalase activity, TBARS, PC, uric acid, and bilirubin increased and GSH declined in all groups in response to acute exercise independent of training status and age. Training improved aerobic capacity, TAC, and GSH at rest and in response to exercise. Age affected basal and exercise-induced responses since adults demonstrated a greater TAC and GSH levels at rest and a greater rise of TBARS, protein carbonyls, and TAC and decline of GSH in response to exercise. Catalase activity, uric acid, and bilirubin responses were comparable among groups. These results suggest that acute exercise, age, and training modulate the antioxidant reserves of the body.

Exercise-intensity dependent alterations in plasma redox status do not reflect skeletal muscle redox-sensitive protein signaling.

Science.gov (United States)

Parker, Lewan; Trewin, Adam; Levinger, Itamar; Shaw, Christopher S; Stepto, Nigel K

2018-04-01

Redox homeostasis and redox-sensitive protein signaling play a role in exercise-induced adaptation. The effects of sprint-interval exercise (SIE), high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CMIE), on post-exercise plasma redox status are unclear. Furthermore, whether post-exercise plasma redox status reflects skeletal muscle redox-sensitive protein signaling is unknown. In a randomized crossover design, eight healthy adults performed a cycling session of HIIE (5×4min at 75% W max ), SIE (4×30s Wingate's), and CMIE work-matched to HIIE (30min at 50% of W max ). Plasma hydrogen peroxide (H 2 O 2 ), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) activity, and catalase activity were measured immediately post, 1h, 2h and 3h post-exercise. Plasma redox status biomarkers were correlated with phosphorylation of skeletal muscle p38-MAPK, JNK, NF-κB, and IκBα protein content immediately and 3h post-exercise. Plasma catalase activity was greater with SIE (56.6±3.8Uml -1 ) compared to CMIE (42.7±3.2, pexercise plasma TBARS and SOD activity significantly (pexercise protocol. A significant positive correlation was detected between plasma catalase activity and skeletal muscle p38-MAPK phosphorylation 3h post-exercise (r=0.40, p=0.04). No other correlations were detected (all p>0.05). Low-volume SIE elicited greater post-exercise plasma catalase activity compared to HIIE and CMIE, and greater H 2 O 2 compared to CMIE. Plasma redox status did not, however, adequately reflect skeletal muscle redox-sensitive protein signaling. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats.

Science.gov (United States)

Adaramoye, Oluwatosin A; Akanni, Olubukola O

2016-01-01

Aspartame (N-L-α-aspartyl-L-phenylalanine-1-methyl ester) (ASP) is a synthetic sweetener used in foods and its safety remains controversial. The study was designed to investigate the effects of long-term administration of aspartame on redox status, lipid profile and biochemical indices in tissues of male Wistar rats. Rats were assigned into four groups and given distilled water (control), aspartame at doses of 15 mg/kg (ASP 1), 35 mg/kg (ASP 2) and 70 mg/kg (ASP 3) daily by oral gavage for consecutive 9 weeks. Administration of ASP 2 and ASP 3 significantly increased the weight of liver and brain, and relative weight of liver of rats. Lipid peroxidation products significantly increased in the kidney, liver and brain of rats at all doses of ASP with concomitant depletion of antioxidant parameters, viz. glutathione-s-transferase, glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione. Furthermore, ASP 2 and ASP 3 significantly increased the levels of gamma glutamyl transferase by 70% and 85%; alanine aminotransferase by 66% and 117%; aspartate aminotransferase by 21% and 48%; urea by 72% and 58% and conjugated bilirubin by 63% and 64%, respectively. Also, ASP 2 and ASP 3 significantly increased the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the rats. Histological findings showed that ASP 2 and ASP 3 caused cyto-architectural changes such as degeneration, monocytes infiltration and necrotic lesions in brain, kidney and liver of rats. Aspartame may induce redox and lipid imbalance in rats via mechanism that involves oxidative stress and depletion of glutathione-dependent system.

How the redox state of tobacco 'Bel-W3' is modified in response to ozone and other environmental factors in a sub-tropical area?

International Nuclear Information System (INIS)

Dias, Ana P.L.; Dafre, Marcelle; Rinaldi, Mirian C.S.; Domingos, Marisa

2011-01-01

This study intended to determine whether the redox state in plants of Nicotiana tabacum 'Bel-W3' fluctuates in response to the environmental factors in a sub-tropical area contaminated by ozone (Sao Paulo, SE - Brazil) and which environmental factors are related to this fluctuation, discussing their biomonitoring efficiency. We comparatively evaluated the indicators of redox state (ascorbic acid, glutathione, superoxide dismutase, ascorbate peroxidase, and glutathione reductase) and leaf injury in 17 field experiments performed in 2008. The redox state was explained by the combined effects of chronic levels of O 3 and meteorological variables 4-6 days prior to the plant sampling. Moderate leaf injury was observed in most cases. The redox state of tobacco decreases few days after their placement in the sub-tropical environment, causing them to become susceptible to oxidative stress imposed by chronic doses of O 3 . Its bioindicator efficiency would not be diminished in such levels of atmospheric contamination. - Research highlights: → Nicotiana tabacum 'Bel-W3' is potentially a bioindicator of O 3 in the sub-tropics. → However, it is unknown if its redox state would affect its bioindicator performance under sub-tropical environmental conditions. → This study revealed that the redox state of tobacco decreases few days after their placement in the sub-tropical environment, causing them to become susceptible to oxidative stress imposed by chronic doses of O 3 . → Therefore, its bioindicator efficiency would not be diminished in such levels of atmospheric contamination. → However, the bioindicator efficiency N. tabacum 'Bel-W3' for biomonitoring O 3 should be regionally modeled in the sub-tropics, based on both its redox state and on the flux of O 3 through stomata, in response to the varying micro-meteorological conditions that govern both physiological processes. - The bioindicator efficiency of tobacco plants is not restrained under chronic doses of O 3 in

Modulation of Erythrocyte Plasma Membrane Redox System Activity by Curcumin

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Prabhakar Singh

2016-01-01

Full Text Available Plasma membrane redox system (PMRS is an electron transport chain system ubiquitously present throughout all cell types. It transfers electron from intracellular substrates to extracellular acceptors for regulation of redox status. Curcumin, isolated from Curcuma longa, has modulatory effects on cellular physiology due to its membrane interaction ability and antioxidant potential. The present study investigates the effect of curcumin on PMRS activity of erythrocytes isolated from Wistar rats in vitro and in vivo and validated through an in silico docking simulation study using Molegro Virtual Docker (MVD. Effects of curcumin were also evaluated on level of glutathione (GSH and the oxidant potential of plasma measured in terms of plasma ferric equivalent oxidative potentials (PFEOP. Results show that curcumin significantly (p<0.01 downregulated the PMRS activity in a dose-dependent manner. Molecular docking results suggest that curcumin interacts with amino acids at the active site cavity of cytochrome b5 reductase, a key constituent of PMRS. Curcumin also increased the GSH level in erythrocytes and plasma while simultaneously decreasing the oxidant potential (PFEOP of plasma. Altered PMRS activity and redox status are associated with the pathophysiology of several health complications including aging and diabetes; hence, the above finding may explain part of the role of curcumin in health beneficial effects.

The impact of oscillating redox conditions: Arsenic immobilisation in contaminated calcareous floodplain soils

International Nuclear Information System (INIS)

Parsons, Christopher T.; Couture, Raoul-Marie; Omoregie, Enoma O.; Bardelli, Fabrizio; Greneche, Jean-Marc; Roman-Ross, Gabriela; Charlet, Laurent

2013-01-01

Arsenic contamination of floodplain soils is extensive and additional fresh arsenic inputs to the pedosphere from human activities are ongoing. We investigate the cumulative effects of repetitive soil redox cycles, which occur naturally during flooding and draining, on a calcareous fluvisol, the native microbial community and arsenic mobility following a simulated contamination event. We show through bioreactor experiments, spectroscopic techniques and modelling that repetitive redox cycling can decrease arsenic mobility during reducing conditions by up to 45%. Phylogenetic and functional analyses of the microbial community indicate that iron cycling is a key driver of observed changes to solution chemistry. We discuss probable mechanisms responsible for the arsenic immobilisation observed in-situ. The proposed mechanisms include, decreased heterotrophic iron reduction due to the depletion of labile particulate organic matter (POM), increases to the proportion of co-precipitated vs. aqueous or sorbed arsenic with α-FeOOH/Fe(OH) 3 and potential precipitation of amorphous ferric arsenate. Highlights: •Oscillating redox conditions and heterotrophic metabolism are implemented in PHREEQC. •Depletion of labile organic matter limits iron reduction and arsenic release. •Amorphous FeAsO 4 ∙2H 2 O precipitation potentially limits arsenic mobility during redox cycling. •Water fluctuating zones may naturally attenuate arsenic liberation during flooding. -- We demonstrate through batch experiments, spectroscopy and modelling that repetitive cycles of oxidation and reduction decrease arsenic mobility in soils during subsequent reducing conditions

A catalytic approach to estimate the redox potential of heme-peroxidases

International Nuclear Information System (INIS)

Ayala, Marcela; Roman, Rosa; Vazquez-Duhalt, Rafael

2007-01-01

The redox potential of heme-peroxidases varies according to a combination of structural components within the active site and its vicinities. For each peroxidase, this redox potential imposes a thermodynamic threshold to the range of oxidizable substrates. However, the instability of enzymatic intermediates during the catalytic cycle precludes the use of direct voltammetry to measure the redox potential of most peroxidases. Here we describe a novel approach to estimate the redox potential of peroxidases, which directly depends on the catalytic performance of the activated enzyme. Selected p-substituted phenols are used as substrates for the estimations. The results obtained with this catalytic approach correlate well with the oxidative capacity predicted by the redox potential of the Fe(III)/Fe(II) couple

Redox balance in elite female athletes: differences based on sport types.

Science.gov (United States)

Arsic, Aleksandra; Vucic, Vesna; Glibetic, Marija; Popovic, Tamara; Debeljak-Martacic, Jasmina; Cubrilo, Dejan; Ahmetovic, Zlatko; Peric, Dusan; Borozan, Suncica; Djuric, Dragan; Barudzic, Nevena; Jakovljevic, Vladimir

2016-01-01

The aim of the present study was to analyze changes in redox balance throughout parameters of oxidative stress and activities of antioxidant enzymes in elite female water polo (N.=15) and football players (N.=19) aged between 20 and 23. Fourteen age-matched sedentary women were also included in the study. Blood sampling was performed to measure levels of lipid peroxidation (MDA), total antioxidant status (TAS), superoxide anion radical (O2-), hydrogen peroxide (H2O2), reduced glutathione (GSH), oxidized glutathione (GSSG), nitrites, superoxide dismutase activity (SOD), catalase activity (CAT) and glutathione-peroxidase activity (GPx). Levels of MDA, TAS, GSSG and H2O2 were significantly higher in athletes than in the control women. Football players had higher levels of O2- than the other two groups. Activity of SOD was higher in water polo players when compared with the football and control groups, CAT was increased in all athletes, while GPx did not differ among groups. Therefore, prolonged intensive training markedly increases oxidative stress in women, which depends on the type of sport. Lower concentration of O2- and increased activity of SOD in water polo players compared to football players suggest that mechanisms of adaptation of antioxidative defense are related to the type of exercise.

Role of glutathione biosynthesis in endothelial dysfunction and fibrosis

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Cristina Espinosa-Díez

2018-04-01

Full Text Available Glutathione (GSH biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL, which is composed of the catalytic (GCLc and the modulatory (GCLm subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice. In murine lung endothelial cells (MLEC derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177 and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+ male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH4. To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+ mice. We observed that obstructed kidneys from Gclc(e/+ mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses. Keywords: Glutamate-cysteine ligase, ROS, Glutathione, Endothelial dysfunction, Kidney Fibrosis

Engineering redox homeostasis to develop efficient alcohol-producing microbial cell factories.

Science.gov (United States)

Zhao, Chunhua; Zhao, Qiuwei; Li, Yin; Zhang, Yanping

2017-06-24

The biosynthetic pathways of most alcohols are linked to intracellular redox homeostasis, which is crucial for life. This crucial balance is primarily controlled by the generation of reducing equivalents, as well as the (reduction)-oxidation metabolic cycle and the thiol redox homeostasis system. As a main oxidation pathway of reducing equivalents, the biosynthesis of most alcohols includes redox reactions, which are dependent on cofactors such as NADH or NADPH. Thus, when engineering alcohol-producing strains, the availability of cofactors and redox homeostasis must be considered. In this review, recent advances on the engineering of cellular redox homeostasis systems to accelerate alcohol biosynthesis are summarized. Recent approaches include improving cofactor availability, manipulating the affinity of redox enzymes to specific cofactors, as well as globally controlling redox reactions, indicating the power of these approaches, and opening a path towards improving the production of a number of different industrially-relevant alcohols in the near future.

Titanium nitride as an electrocatalyst for V(II)/V(III) redox couples in all-vanadium redox flow batteries

International Nuclear Information System (INIS)

Yang, Chunmei; Wang, Haining; Lu, Shanfu; Wu, Chunxiao; Liu, Yiyang; Tan, Qinglong; Liang, Dawei; Xiang, Yan

2015-01-01

Titanium nitride nanoparticles (TiN NPs) are proposed as a novel catalyst towards the V(II)/V(III) redox pair for the negative electrode in vanadium redox flow batteries (VRFB). Electrochemical properties of TiN NPs were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results show that TiN NPs demonstrate better electrochemical activity and reversibility for the processes of V(II)/V(III) redox couples as compared with the graphite NPs. TiN NPs facilitate the charge transfer in the V(II)/V(III) redox reaction. Performance of a VRFB using a TiN NPs coated carbon paper as a negative electrode is much higher than that of a VRFB with a raw carbon paper electrode. The columbic efficiency (CE), the voltage efficiency (VE) and the energy efficiency (EE) of the VRFB single cell at charge-discharge current density of 30 mA/cm 2 are 91.74%, 89.11% and 81.74%, respectively. During a 50 charge-discharge cycles test, the CE values of VRFB with TiN NPs consistently remain higher than 90%.

Redox Species of Redox Flow Batteries: A Review.

Science.gov (United States)

Pan, Feng; Wang, Qing

2015-11-18

Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its modular design, good scalability and flexible operation. The biggest challenge of the redox flow battery is the low energy density. The redox active species is the most important component in redox flow batteries, and the redox potential and solubility of redox species dictate the system energy density. This review is focused on the recent development of redox species. Different categories of redox species, including simple inorganic ions, metal complexes, metal-free organic compounds, polysulfide/sulfur and lithium storage active materials, are reviewed. The future development of redox species towards higher energy density is also suggested.

Redox Species of Redox Flow Batteries: A Review

Directory of Open Access Journals (Sweden)

Feng Pan

2015-11-01

Full Text Available Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its modular design, good scalability and flexible operation. The biggest challenge of the redox flow battery is the low energy density. The redox active species is the most important component in redox flow batteries, and the redox potential and solubility of redox species dictate the system energy density. This review is focused on the recent development of redox species. Different categories of redox species, including simple inorganic ions, metal complexes, metal-free organic compounds, polysulfide/sulfur and lithium storage active materials, are reviewed. The future development of redox species towards higher energy density is also suggested.

Chloroplastic thioredoxin-f and thioredoxin-m1/4 play important roles in brassinosteroids-induced changes in CO2 assimilation and cellular redox homeostasis in tomato

OpenAIRE

Cheng, Fei; Zhou, Yan-Hong; Xia, Xiao-Jian; Shi, Kai; Zhou, Jie; Yu, Jing-Quan

2014-01-01

Chloroplast thioredoxins (TRXs) and glutathione function as redox messengers in the regulation of photosynthesis. In this work, the roles of chloroplast TRXs in brassinosteroids (BRs)-induced changes in cellular redox homeostasis and CO2 assimilation were studied in the leaves of tomato plants. BRs-deficient d ^im plants showed decreased transcripts of TRX-f, TRX-m2, TRX-m1/4, and TRX-x, while exogenous BRs significantly induced CO2 assimilation and the expression of TRX-f, TRX-m2, TRX-m1/4, ...

A redox-dependent dimerization switch regulates activity and tolerance for reactive oxygen species of barley seed glutathione peroxidase

DEFF Research Database (Denmark)

Navrot, Nicolas; Skjoldager, Nicklas; Bunkenborg, Jakob

2015-01-01

Monomeric and dimeric forms of recombinant barley (Hordeum vulgare subsp. vulgare) glutathione peroxidase 2 (HvGpx2) are demonstrated to display distinctly different functional properties in vitro. Monomeric HvGpx2 thus has five fold higher catalytic efficiency than the dimer towards tert-butyl h...

The mechanism behind redox instability of anodes in high-temperature SOFCs

DEFF Research Database (Denmark)

Klemensø, Trine; Chung, Charissa; Larsen, Peter Halvor

2005-01-01

Bulk expansion of the anode upon oxidation is considered to be responsible for the lack of redox stability in high-temperature solid oxide fuel cells (SOFCs). The bulk expansion of nickel-yttria stabilized zirconia (YSZ) anode materials was measured by dilatometry as a function of sample geometry......, ceramic component, temperature, and temperature cycling. The strength of the ceramic network and the degree of Ni redistribution appeared to be key parameters of the redox behavior. A model of the redox mechanism in nickel-YSZ anodes was developed based on the dilatometry data and macro...

How the redox state of tobacco 'Bel-W3' is modified in response to ozone and other environmental factors in a sub-tropical area?

Energy Technology Data Exchange (ETDEWEB)

Dias, Ana P.L.; Dafre, Marcelle; Rinaldi, Mirian C.S. [Instituto de Botanica, Caixa Postal 3005, 01061-970 Sao Paulo, SP (Brazil); Domingos, Marisa, E-mail: mmingos@superig.com.b [Instituto de Botanica, Caixa Postal 3005, 01061-970 Sao Paulo, SP (Brazil)

2011-02-15

This study intended to determine whether the redox state in plants of Nicotiana tabacum 'Bel-W3' fluctuates in response to the environmental factors in a sub-tropical area contaminated by ozone (Sao Paulo, SE - Brazil) and which environmental factors are related to this fluctuation, discussing their biomonitoring efficiency. We comparatively evaluated the indicators of redox state (ascorbic acid, glutathione, superoxide dismutase, ascorbate peroxidase, and glutathione reductase) and leaf injury in 17 field experiments performed in 2008. The redox state was explained by the combined effects of chronic levels of O{sub 3} and meteorological variables 4-6 days prior to the plant sampling. Moderate leaf injury was observed in most cases. The redox state of tobacco decreases few days after their placement in the sub-tropical environment, causing them to become susceptible to oxidative stress imposed by chronic doses of O{sub 3}. Its bioindicator efficiency would not be diminished in such levels of atmospheric contamination. - Research highlights: Nicotiana tabacum 'Bel-W3' is potentially a bioindicator of O{sub 3} in the sub-tropics. However, it is unknown if its redox state would affect its bioindicator performance under sub-tropical environmental conditions. This study revealed that the redox state of tobacco decreases few days after their placement in the sub-tropical environment, causing them to become susceptible to oxidative stress imposed by chronic doses of O{sub 3}. Therefore, its bioindicator efficiency would not be diminished in such levels of atmospheric contamination. However, the bioindicator efficiency N. tabacum 'Bel-W3' for biomonitoring O{sub 3} should be regionally modeled in the sub-tropics, based on both its redox state and on the flux of O{sub 3} through stomata, in response to the varying micro-meteorological conditions that govern both physiological processes. - The bioindicator efficiency of tobacco plants is not

High-energy redox-flow batteries with hybrid metal foam electrodes.

Science.gov (United States)

Park, Min-Sik; Lee, Nam-Jin; Lee, Seung-Wook; Kim, Ki Jae; Oh, Duk-Jin; Kim, Young-Jun

2014-07-09

A nonaqueous redox-flow battery employing [Co(bpy)3](+/2+) and [Fe(bpy)3](2+/3+) redox couples is proposed for use in large-scale energy-storage applications. We successfully demonstrate a redox-flow battery with a practical operating voltage of over 2.1 V and an energy efficiency of 85% through a rational cell design. By utilizing carbon-coated Ni-FeCrAl and Cu metal foam electrodes, the electrochemical reactivity and stability of the nonaqueous redox-flow battery can be considerably enhanced. Our approach intoduces a more efficient conversion of chemical energy into electrical energy and enhances long-term cell durability. The cell exhibits an outstanding cyclic performance of more than 300 cycles without any significant loss of energy efficiency. Considering the increasing demands for efficient energy storage, our achievement provides insight into a possible development pathway for nonaqueous redox-flow batteries with high energy densities.

Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

Energy Technology Data Exchange (ETDEWEB)

Putt, David A.; Zhong, Qing; Lash, Lawrence H., E-mail: l.h.lash@wayne.edu

2012-01-15

Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox status in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter. �

Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

International Nuclear Information System (INIS)

Putt, David A.; Zhong, Qing; Lash, Lawrence H.

2012-01-01

Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox status in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter. �

Exogenous Spermidine Alleviates Low Temperature Injury in Mung Bean (Vigna radiata L. Seedlings by Modulating Ascorbate-Glutathione and Glyoxalase Pathway

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Kamrun Nahar

2015-12-01

Full Text Available The role of exogenous spermidine (Spd in alleviating low temperature (LT stress in mung bean (Vigna radiata L. cv. BARI Mung-3 seedlings has been investigated. Low temperature stress modulated the non-enzymatic and enzymatic components of ascorbate-glutathione (AsA-GSH cycle, increased H2O2 content and lipid peroxidation, which indicate oxidative damage of seedlings. Low temperature reduced the leaf relative water content (RWC and destroyed leaf chlorophyll, which inhibited seedlings growth. Exogenous pretreatment of Spd in LT-affected seedlings significantly increased the contents of non-enzymatic antioxidants of AsA-GSH cycle, which include AsA and GSH. Exogenous Spd decreased dehydroascorbate (DHA, increased AsA/DHA ratio, decreased glutathione disulfide (GSSG and increased GSH/GSSG ratio under LT stress. Activities of AsA-GSH cycle enzymes such as ascorbate peroxidase (APX, monodehydroascorbate reductase (MDHAR, dehydroascorbate reductase (DHAR and glutathione reductase (GR increased after Spd pretreatment in LT affected seedlings. Thus, the oxidative stress was reduced. Protective effects of Spd are also reflected from reduction of methylglyoxal (MG toxicity by improving glyoxalase cycle components, and by maintaining osmoregulation, water status and improved seedlings growth. The present study reveals the vital roles of AsA-GSH and glyoxalase cycle in alleviating LT injury.

Redox-capacitor to connect electrochemistry to redox-biology.

Science.gov (United States)

Kim, Eunkyoung; Leverage, W Taylor; Liu, Yi; White, Ian M; Bentley, William E; Payne, Gregory F

2014-01-07

It is well-established that redox-reactions are integral to biology for energy harvesting (oxidative phosphorylation), immune defense (oxidative burst) and drug metabolism (phase I reactions), yet there is emerging evidence that redox may play broader roles in biology (e.g., redox signaling). A critical challenge is the need for tools that can probe biologically-relevant redox interactions simply, rapidly and without the need for a comprehensive suite of analytical methods. We propose that electrochemistry may provide such a tool. In this tutorial review, we describe recent studies with a redox-capacitor film that can serve as a bio-electrode interface that can accept, store and donate electrons from mediators commonly used in electrochemistry and also in biology. Specifically, we (i) describe the fabrication of this redox-capacitor from catechols and the polysaccharide chitosan, (ii) discuss the mechanistic basis for electron exchange, (iii) illustrate the properties of this redox-capacitor and its capabilities for promoting redox-communication between biology and electrodes, and (iv) suggest the potential for enlisting signal processing strategies to "extract" redox information. We believe these initial studies indicate broad possibilities for enlisting electrochemistry and signal processing to acquire "systems level" redox information from biology.

Thioredoxin-dependent Redox Regulation of Chloroplastic Phosphoglycerate Kinase from Chlamydomonas reinhardtii*

Science.gov (United States)

Morisse, Samuel; Michelet, Laure; Bedhomme, Mariette; Marchand, Christophe H.; Calvaresi, Matteo; Trost, Paolo; Fermani, Simona; Zaffagnini, Mirko; Lemaire, Stéphane D.

2014-01-01

In photosynthetic organisms, thioredoxin-dependent redox regulation is a well established mechanism involved in the control of a large number of cellular processes, including the Calvin-Benson cycle. Indeed, 4 of 11 enzymes of this cycle are activated in the light through dithiol/disulfide interchanges controlled by chloroplastic thioredoxin. Recently, several proteomics-based approaches suggested that not only four but all enzymes of the Calvin-Benson cycle may withstand redox regulation. Here, we characterized the redox features of the Calvin-Benson enzyme phosphoglycerate kinase (PGK1) from the eukaryotic green alga Chlamydomonas reinhardtii, and we show that C. reinhardtii PGK1 (CrPGK1) activity is inhibited by the formation of a single regulatory disulfide bond with a low midpoint redox potential (−335 mV at pH 7.9). CrPGK1 oxidation was found to affect the turnover number without altering the affinity for substrates, whereas the enzyme activation appeared to be specifically controlled by f-type thioredoxin. Using a combination of site-directed mutagenesis, thiol titration, mass spectrometry analyses, and three-dimensional modeling, the regulatory disulfide bond was shown to involve the not strictly conserved Cys227 and Cys361. Based on molecular mechanics calculation, the formation of the disulfide is proposed to impose structural constraints in the C-terminal domain of the enzyme that may lower its catalytic efficiency. It is therefore concluded that CrPGK1 might constitute an additional light-modulated Calvin-Benson cycle enzyme with a low activity in the dark and a TRX-dependent activation in the light. These results are also discussed from an evolutionary point of view. PMID:25202015

Ebselen, a useful tool for understanding cellular redox biology and a promising drug candidate for use in human diseases.

Science.gov (United States)

Noguchi, Noriko

2016-04-01

Ebselen is an organoselenium compound with glutathione peroxidase (GPx)-like hydroperoxide reducing activity. Moreover, ebselen has its own unique reactivity, with functions that GPx does not have, since it reacts with many kinds of thiols other than glutathione. Ebselen may affect the thioredoxin systems, through which it may contribute to regulation of cell function. With high reactivity toward thiols, hydroperoxides, and peroxynitrite, ebselen has been used as a useful tool in research on cellular redox mechanisms. Unlike α-tocopherol, ebselen does not scavenge lipid peroxyl radicals, which is another advantage of ebselen for use as a research tool in comparison with radical scavenging antioxidants. Selenium is not released from the ebselen molecule, which explains the low toxicity of ebselen. To further understand the mechanism of cellular redox biology, it should be interesting to compare the effects of ebselen with that of selenoprotein P, which supplies selenium to GPx. New medical applications of ebselen as a drug candidate for human diseases such as cancer and diabetes mellitus as well as brain stroke and ischemia will be expected. Copyright © 2015 Elsevier Inc. All rights reserved.

An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients.

Science.gov (United States)

Parlanti, Eleonora; Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara; Zijno, Andrea; D'Errico, Mariarosaria; Simonelli, Valeria; Sanchez, Massimo; Fattibene, Paola; Falchi, Mario; Dogliotti, Eugenia

2015-12-01

Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O₂₋• and H₂O₂ being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance (¹H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer risk. The increased MN frequency was not affected by inhibition of ROS to normal levels by N-acetyl-L-cysteine. Copyright © 2015 Elsevier B.V. All rights reserved.

Overexpression of the transcription factor Yap1 modifies intracellular redox conditions and enhances recombinant protein secretion

Directory of Open Access Journals (Sweden)

Marizela Delic

2014-10-01

Full Text Available Oxidative folding of secretory proteins in the endoplasmic reticulum (ER is a redox active process, which also impacts the redox conditions in the cytosol. As the transcription factor Yap1 is involved in the transcriptional response to oxidative stress, we investigate its role upon the production of secretory proteins, using the yeast Pichia pastoris as model, and report a novel important role of Yap1 during oxidative protein folding. Yap1 is needed for the detoxification of reactive oxygen species (ROS caused by increased oxidative protein folding. Constitutive co-overexpression of PpYAP1 leads to increased levels of secreted recombinant protein, while a lowered Yap1 function leads to accumulation of ROS and strong flocculation. Transcriptional analysis revealed that more than 150 genes were affected by overexpression of YAP1, in particular genes coding for antioxidant enzymes or involved in oxidation-reduction processes. By monitoring intracellular redox conditions within the cytosol and the ER using redox-sensitive roGFP1 variants, we could show that overexpression of YAP1 restores cellular redox conditions of protein-secreting P. pastoris by reoxidizing the cytosolic redox state to the levels of the wild type. These alterations are also reflected by increased levels of oxidized intracellular glutathione (GSSG in the YAP1 co-overexpressing strain. Taken together, these data indicate a strong impact of intracellular redox balance on the secretion of (recombinant proteins without affecting protein folding per se. Re-establishing suitable redox conditions by tuning the antioxidant capacity of the cell reduces metabolic load and cell stress caused by high oxidative protein folding load, thereby increasing the secretion capacity.

Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing.

Science.gov (United States)

Sowden, Rebecca J; Trotter, Katherine D; Dunbar, Lynsey; Craig, Gemma; Erdemli, Omer; Spickett, Corinne M; Reglinski, John

2013-02-01

A series of simple copper N(2)S(2) macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

Sb(V reactivity with human blood components: redox effects.

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Silvana López

Full Text Available We assessed the reactivity of Sb(V in human blood. Sb(V reactivity was determined using an HPLC-HG-AFS hyphenated system. Sb(V was partially reduced to Sb(III in blood incubation experiments; however, Sb(III was a highly unstable species. The addition of 0.1 mol L(-1 EDTA prevented Sb(III oxidation, thus enabling the detection of the reduction of Sb(V to Sb(III. The transformation of Sb(V to Sb(III in human whole blood was assessed because the reduction of Sb(V in human blood may likely generate redox side effects. Our results indicate that glutathione was the reducing agent in this reaction and that Sb(V significantly decreased the GSH/GSSG ratio from 0.32 ± 0.09 to 0.07 ± 0.03. Moreover, the presence of 200 ng mL(-1 of Sb(V increased the activity of superoxide dismutase from 4.4 ± 0.1 to 7.0 ± 0.4 U mL(-1 and decreased the activity of glutathione peroxidase from 62 ± 1 to 34 ± 2 nmol min(-1 mL(-1.

Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment.

Science.gov (United States)

Holroyd, K J; Buhl, R; Borok, Z; Roum, J H; Bokser, A D; Grimes, G J; Czerski, D; Cantin, A M; Crystal, R G

1993-10-01

Concentrations of glutathione, a ubiquitous tripeptide with immune enhancing and antioxidant properties, are decreased in the blood and lung epithelial lining fluid of human immunodeficiency virus (HIV) seropositive individuals. Since the lung is the most common site of infection in those who progress to AIDS it is rational to consider whether it is possible to safely augment glutathione levels in the epithelial lining fluid of HIV seropositive individuals, thus potentially improving local host defence. Purified reduced glutathione was delivered by aerosol to HIV seropositive individuals (n = 14) and the glutathione levels in lung epithelial lining fluid were compared before and at one, two, and three hours after aerosol administration. Before treatment total glutathione concentrations in the epithelial lining fluid were approximately 60% of controls. After three days of twice daily doses each of 600 mg reduced glutathione, total glutathione levels in the epithelial lining fluid increased and remained in the normal range for at least three hours after treatment. Strikingly, even though > 95% of the glutathione in the aerosol was in its reduced form, the percentage of oxidised glutathione in epithelial lining fluid increased from 5% before treatment to about 40% three hours after treatment, probably reflecting the use of glutathione as an antioxidant in vivo. No adverse effects were observed. It is feasible and safe to use aerosolised reduced glutathione to augment the deficient glutathione levels of the lower respiratory tract of HIV seropositive individuals. It is rational to evaluate further the efficacy of this tripeptide in improving host defence in HIV seropositive individuals.

Acrolein toxicity involves oxidative stress caused by glutathione depletion in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Kwolek-Mirek, M; Bednarska, S; Bartosz, G; Biliński, T

2009-08-01

Exposure of yeast cells to allyl alcohol results in intracellular production of acrolein. The toxicity of so formed acrolein involves oxidative stress, as (1) strains deficient in antioxidant defense are hypersensitive to allyl alcohol, (2) exposure to allyl alcohol increases the level of thiobarbituric-acid-reactive substances and decreases glutathione level in the cells, (3) hypoxic and anoxic atmosphere and antioxidants protect against allyl alcohol toxicity, and (4) allyl alcohol causes activation of Yap1p. No increased formation of reactive oxygen species was detected in cells exposed to allyl alcohol, so oxidative stress is due to depletion of cellular thiols and thus alteration in the redox state of yeast cells.

Redox proteomics of tomato in response to Pseudomonas syringae infection

Science.gov (United States)

Balmant, Kelly Mayrink; Parker, Jennifer; Yoo, Mi-Jeong; Zhu, Ning; Dufresne, Craig; Chen, Sixue

2015-01-01

Unlike mammals with adaptive immunity, plants rely on their innate immunity based on pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) for pathogen defense. Reactive oxygen species, known to play crucial roles in PTI and ETI, can perturb cellular redox homeostasis and lead to changes of redox-sensitive proteins through modification of cysteine sulfhydryl groups. Although redox regulation of protein functions has emerged as an important mechanism in several biological processes, little is known about redox proteins and how they function in PTI and ETI. In this study, cysTMT proteomics technology was used to identify similarities and differences of protein redox modifications in tomato resistant (PtoR) and susceptible (prf3) genotypes in response to Pseudomonas syringae pv tomato (Pst) infection. In addition, the results of the redox changes were compared and corrected with the protein level changes. A total of 90 potential redox-regulated proteins were identified with functions in carbohydrate and energy metabolism, biosynthesis of cysteine, sucrose and brassinosteroid, cell wall biogenesis, polysaccharide/starch biosynthesis, cuticle development, lipid metabolism, proteolysis, tricarboxylic acid cycle, protein targeting to vacuole, and oxidation–reduction. This inventory of previously unknown protein redox switches in tomato pathogen defense lays a foundation for future research toward understanding the biological significance of protein redox modifications in plant defense responses. PMID:26504582

Glutathione-binding site of a bombyx mori theta-class glutathione transferase.

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M D Tofazzal Hossain

Full Text Available The glutathione transferase (GST superfamily plays key roles in the detoxification of various xenobiotics. Here, we report the isolation and characterization of a silkworm protein belonging to a previously reported theta-class GST family. The enzyme (bmGSTT catalyzes the reaction of glutathione with 1-chloro-2,4-dinitrobenzene, 1,2-epoxy-3-(4-nitrophenoxy-propane, and 4-nitrophenethyl bromide. Mutagenesis of highly conserved residues in the catalytic site revealed that Glu66 and Ser67 are important for enzymatic function. These results provide insights into the catalysis of glutathione conjugation in silkworm by bmGSTT and into the metabolism of exogenous chemical agents.

Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment

Science.gov (United States)

Chen, Fengqian; Zhang, Jinming; Wang, Lu; Wang, Yitao; Chen, Meiwan

2015-09-01

The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-α-tocopheryl polyethylene glycol 1000-poly(β-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 +/- 2.5 mV to +22.5 +/- 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side-effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy.The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 m

Thiol Redox Sensitivity of Two Key Enzymes of Heme Biosynthesis and Pentose Phosphate Pathways: Uroporphyrinogen Decarboxylase and Transketolase

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Brian McDonagh

2013-01-01

Full Text Available Uroporphyrinogen decarboxylase (Hem12p and transketolase (Tkl1p are key mediators of two critical processes within the cell, heme biosynthesis, and the nonoxidative part of the pentose phosphate pathway (PPP. The redox properties of both Hem12p and Tkl1p from Saccharomyces cerevisiae were investigated using proteomic techniques (SRM and label-free quantification and biochemical assays in cell extracts and in vitro with recombinant proteins. The in vivo analysis revealed an increase in oxidized Cys-peptides in the absence of Grx2p, and also after treatment with H2O2 in the case of Tkl1p, without corresponding changes in total protein, demonstrating a true redox response. Out of three detectable Cys residues in Hem12p, only the conserved residue Cys52 could be modified by glutathione and efficiently deglutathionylated by Grx2p, suggesting a possible redox control mechanism for heme biosynthesis. On the other hand, Tkl1p activity was sensitive to thiol redox modification and although Cys622 could be glutathionylated to a limited extent, it was not a natural substrate of Grx2p. The human orthologues of both enzymes have been involved in certain cancers and possess Cys residues equivalent to those identified as redox sensitive in yeast. The possible implication for redox regulation in the context of tumour progression is put forward.

Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

Science.gov (United States)

Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

2015-07-01

Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility

International Nuclear Information System (INIS)

Aw, Tak Yee

2005-01-01

The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium

Effect of time-dependent cryotherapy on redox balance of quadriceps injuries.

Science.gov (United States)

Silva, Marco Aurélio dos Santos; Carvalho, Taiara Ramos de; Cruz, Amanda Cristina Marques Barros da; Jesus, Lennon Rafael Guedine de; Silva Neto, Larissa Alexsandra da; Trajano, Eduardo Tavares Lima; Bezerra, Frank Silva

2016-02-01

Muscle trauma represents a high number of injuries in professional sport and recreation and may occur through several mechanisms. This study aims at analyzing time-dependent effects of cryotherapy on the redox balance in lesioned quadriceps muscles in F1 mice. Twenty male F1 mice were divided into five groups: (a) animals were not subjected to muscle lesioning or treatment (CTR); (b) quadriceps muscle was lesioned without treatment (L); (c) quadriceps muscle was lesioned and treated with cryotherapy for 5 min (LC5); (d) quadriceps muscle was lesioned and treated with cryotherapy for 20 min (LC20); and quadriceps muscle was lesioned and treated with cryotherapy for 40 min (LC40). The mice were euthanized; the quadriceps muscles were collected and subjected to analyses for levels of protein, hydroperoxides, nitrite, catalase (CAT) activity, oxidized glutathione (GSSG) and reduced glutathione (GSH). Protein levels were reduced in L (-39%; p cryotherapy does not improve the oxidative stress in lesioned muscles. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of iron redox cycling on organo-mineral associations in Arctic tundra soil

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Herndon, Elizabeth; AlBashaireh, Amineh; Singer, David; Roy Chowdhury, Taniya; Gu, Baohua; Graham, David

2017-06-01

Arctic tundra stores large quantities of soil organic matter under varying redox conditions. As the climate warms, these carbon reservoirs are susceptible to increased rates of decomposition and release to the atmosphere as the greenhouse gases carbon dioxide (CO2) and methane (CH4). Geochemical interactions between soil organic matter and minerals influence decomposition in many environments but remain poorly understood in Arctic tundra systems and are not considered in decomposition models. The accumulation of iron (Fe) oxyhydroxides and organo-iron precipitates at redox interfaces may be particularly important for carbon cycling given that ferric iron [Fe(III)] species can enhance decomposition by serving as terminal electron acceptors in anoxic soils or inhibit microbial decomposition by binding organic molecules. Here, we examine chemical properties of solid-phase Fe and organic matter in organic and mineral horizons within the seasonally thawed active layer of Arctic tundra on the North Slope of Alaska. Spectroscopic techniques, including micro-X-ray fluorescence (μXRF) mapping, micro-X-ray absorption near-edge structure (μXANES) spectroscopy, and Fourier transform infrared spectroscopy (FTIR), were coupled with chemical sequential extractions and physical density fractionations to evaluate the spatial distribution and speciation of Fe-bearing phases and associated organic matter in soils. Organic horizons were enriched in poorly crystalline and crystalline iron oxides, and approximately 60% of total Fe stored in organic horizons was calculated to derive from upward translocation from anoxic mineral horizons. Ferrihydrite and goethite were present as coatings on mineral grains and plant debris, and in aggregates with clays and particulate organic matter. Minor amounts of ferrous iron [Fe(II)] were present in iron sulfides (i.e., pyrite and greigite) in mineral horizon soils and iron phosphates (vivianite) in organic horizons. Concentrations of organic

Redox and pH Responsive Poly (Amidoamine Dendrimer-Heparin Conjugates via Disulfide Linkages for Letrozole Delivery

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Thanh Luan Nguyen

2017-01-01

Full Text Available Heparin (Hep conjugated to poly (amidoamine dendrimer G3.5 (P via redox-sensitive disulfide bond (P-SS-Hep was studied. The redox and pH dual-responsive nanocarriers were prepared by a simple method that minimized many complex steps as previous studies. The functional characterization of G3.5 coated Hep was investigated by the proton nuclear magnetic resonance spectroscopy. The size and formation were characterized by the dynamic light scattering, zeta potential, and transmission electron microscopy. P-SS-Hep was spherical in shape with average diameter about 11 nm loaded with more than 20% letrozole. This drug carrier could not only eliminate toxicity to cells and improve the drugs solubility but also increase biocompatibility of the system under reductive environment of glutathione. In particular, P-SS-Hep could enhance the effectiveness of cancer therapy after removing Hep from the surface. These results demonstrated that the P-SS-Hep conjugates could be a promising candidate as redox and pH responsive nanocarriers for cancer chemotherapy.

Cyclic voltammetric study of the redox system of glutathione using the disulfide bond reductant tris(2-carboxyethyl)phosphine

Czech Academy of Sciences Publication Activity Database

Kizek, René; Vacek, Jan; Trnková, L.; Jelen, František

2004-01-01

Roč. 63, 1-2 (2004), s. 19-24 ISSN 1567-5394 R&D Projects: GA AV ČR IAA1163201; GA ČR GA203/02/0422 Institutional research plan: CEZ:AV0Z5004920 Keywords : voltammetry * hanging mercury drop electrode (HMDE) * glutathione (GSH, GSSG) Subject RIV: BO - Biophysics Impact factor: 2.261, year: 2004

Radiation-induced non-equilibrium redox chemistry of plutonium: implications for environmental migration

International Nuclear Information System (INIS)

Haschke, J.M.; Siekhaus, W.J.

2009-01-01

Static concentrations of plutonium oxidation states in solution and at surfaces in oxide-water systems are identified as non-equilibrium steady states. These kinetically controlled systems are described by redox cycles based on irreversible disproportionation of Pu(IV), Pu(V), and Pu(VI) in OH-bridged intermediate complexes and at OH-covered oxide surfaces. Steady state is fixed by continuous redox cycles driven by radioactivity-promoted electron-transfer and energetically favorable reactions of Pu(III) and Pu(VII) disproportionation products with H2O. A model based on the redox cycles accounts for the high steady-state (Pu) coexisting with Pu(IV) hydrous oxide at pH 0-15 and for predominance of Pu(V) and Pu(VI) in solution. The steady-state (Pu) depends on pH and the surface area of oxide in solution, but not on the initial Pu oxidation state. PuO 2+x formation is attributed to high Pu(V) concentrations existing at water-exposed oxide surfaces. Results infer that migration of Pu in an aqueous environment is controlled by kinetic factors unique to that site and that the predominant oxidation states in solution are Pu(V) and Pu(VI)

New Supercapacitors Based on the Synergetic Redox Effect between Electrode and Electrolyte

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You Zhang

2016-08-01

Full Text Available Redox electrolytes can provide significant enhancement of capacitance for supercapacitors. However, more important promotion comes from the synergetic effect and matching between the electrode and electrolyte. Herein, we report a novel electrochemical system consisted of a polyanilline/carbon nanotube composite redox electrode and a hydroquinone (HQ redox electrolyte, which exhibits a specific capacitance of 7926 F/g in a three-electrode system when the concentration of HQ in H2SO4 aqueous electrolyte is 2 mol/L, and the maximum energy density of 114 Wh/kg in two-electrode symmetric configuration. Moreover, the specific capacitance retention of 96% after 1000 galvanostatic charge/discharge cycles proves an excellent cyclic stability. These ultrahigh performances of the supercapacitor are attributed to the synergistic effect both in redox polyanilline-based electrolyte and the redox hydroquinone electrode.

Menadione stress in Saccharomyces cerevisiae strains deficient in the glutathione transferases.

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Castro, F A V; Herdeiro, R S; Panek, A D; Eleutherio, E C A; Pereira, M D

2007-02-01

Using S. cerevisiae as a eukaryotic cell model we have analyzed the involvement of both glutathione transferase isoforms, Gtt1 and Gtt2, in constitutive resistance and adaptive response to menadione, a quinone which can exert its toxicity as redox cycling and/or electrophiles. The detoxification properties, of these enzymes, have also been analyzed by the appearance of S-conjugates in the media. Direct exposure to menadione (20 mM/60 min) showed to be lethal for cells deficient on both Gtt1 and Gtt2 isoforms. However, after pre-treatment with a low menadione concentration, cells deficient in Gtt2 displayed reduced ability to acquire tolerance when compared with the control and the Gtt1 deficient strains. Analyzing the toxic effects of menadione we observed that the gtt2 mutant showed no reduction in lipid peroxidation levels. Moreover, measuring the levels of intracellular oxidation during menadione stress we have shown that the increase of this oxidative stress parameter was due to the capacity menadione possesses in generating reactive oxygen species (ROS) and that both GSH and Gtt2 isoform were required to enhance ROS production. Furthermore, the efflux of the menadione-GSH conjugate, which is related with detoxification of xenobiotic pathways, was not detected in the gtt2 mutant. Taken together, these results suggest that acquisition of tolerance against stress generated by menadione and the process of detoxification through S-conjugates are dependent upon Gtt2 activity. This assessment was corroborated by the increase of GTT2 expression, and not of GTT1, after menadione treatment.

Biochemical and redox characterization of the mediator complex and its associated transcription factor GeBPL, a GLABROUS1 enhancer binding protein.

Science.gov (United States)

Shaikhali, Jehad; Davoine, Céline; Brännström, Kristoffer; Rouhier, Nicolas; Bygdell, Joakim; Björklund, Stefan; Wingsle, Gunnar

2015-06-15

The eukaryotic mediator integrates regulatory signals from promoter-bound transcription factors (TFs) and transmits them to RNA polymerase II (Pol II) machinery. Although redox signalling is important in adjusting plant metabolism and development, nothing is known about a possible redox regulation of mediator. In the present study, using pull-down and yeast two-hybrid assays, we demonstrate the association of mediator (MED) subunits MED10a, MED28 and MED32 with the GLABROUS1 (GL1) enhancer-binding protein-like (GeBPL), a plant-specific TF that binds a promoter containing cryptochrome 1 response element 2 (CryR2) element. All the corresponding recombinant proteins form various types of covalent oligomers linked by intermolecular disulfide bonds that are reduced in vitro by the thioredoxin (TRX) and/or glutathione/glutaredoxin (GRX) systems. The presence of recombinant MED10a, MED28 and MED32 subunits or changes of its redox state affect the DNA-binding capacity of GeBPL suggesting that redox-driven conformational changes might modulate its activity. Overall, these results advance our understanding of how redox signalling affects transcription and identify mediator as a novel actor in redox signalling pathways, relaying or integrating redox changes in combination with specific TFs as GeBPL. © The Authors Journal compilation © 2015 Biochemical Society.

Highly sensitive and label-free electrochemical detection of microRNAs based on triple signal amplification of multifunctional gold nanoparticles, enzymes and redox-cycling reaction.

Science.gov (United States)

Liu, Lin; Xia, Ning; Liu, Huiping; Kang, Xiaojing; Liu, Xiaoshuan; Xue, Chan; He, Xiaoling

2014-03-15

MicroRNAs (miRNAs) are believed to be important for cancer diagnosis and prognosis, serving as reliable molecular biomarkers. In this work, we presented a label-free and highly sensitive electrochemical genosensor for miRNAs detection with the triple signal amplification of gold nanoparticles (AuNPs), alkaline phosphatase (ALP) and p-aminophenol (p-AP) redox cycling. The label-free strategy is based on the difference in the structures of RNA and DNA. Specifically, miRNAs were first captured by the pre-immobilized DNA probes on a gold electrode. Next, the cis-diol group of ribose sugar at the end of the miRNAs chain allowed 3-aminophenylboronic acid (APBA)/biotin-modified multifunctional AuNPs (denoted as APBA-biotin-AuNPs) to be attached through the formation of a boronate ester covalent bond, which facilitated the capture of streptavidin-conjugated alkaline phosphatase (SA-ALP) via the biotin-streptavidin interaction. After the addition of the 4-aminophenylphosphate (p-APP) substrate, the enzymatic conversion from p-APP to p-AP occurred. The resulting p-AP could be cycled by a chemical reducing reagent after its electro-oxidization on the electrode (known as p-AP redox cycling), thus enabling an increase in the anodic current. As a result, the current increased linearly with the miRNAs concentration over a range of 10 fM-5 pM, and a detection limit of 3 fM was achieved. We believe that this work will be valuable for the design of new types of label-free and sensitive electrochemical biosensors. © 2013 Published by Elsevier B.V.

Redox Cycling, pH Dependence, and Ligand Effects of Mn(III) in Oxalate Decarboxylase from Bacillus subtilis.

Science.gov (United States)

Twahir, Umar T; Ozarowski, Andrew; Angerhofer, Alexander

2016-11-29

This contribution describes electron paramagnetic resonance (EPR) experiments on Mn(III) in oxalate decarboxylase of Bacillus subtilis, an interesting enzyme that catalyzes the redox-neutral dissociation of oxalate into formate and carbon dioxide. Chemical redox cycling provides strong evidence that both Mn centers can be oxidized, although the N-terminal Mn(II) appears to have the lower reduction potential and is most likely the carrier of the +3 oxidation state under moderate oxidative conditions, in agreement with the general view that it represents the active site. Significantly, Mn(III) was observed in untreated OxDC in succinate and acetate buffers, while it could not be directly observed in citrate buffer. Quantitative analysis showed that up to 16% of the EPR-visible Mn is in the +3 oxidation state at low pH in the presence of succinate buffer. The fine structure and hyperfine structure parameters of Mn(III) are affected by small carboxylate ligands that can enter the active site and have been recorded for formate, acetate, and succinate. The results from a previous report [Zhu, W., et al. (2016) Biochemistry 55, 429-434] could therefore be reinterpreted as evidence of formate-bound Mn(III) after the enzyme is allowed to turn over oxalate. The pH dependence of the Mn(III) EPR signal compares very well with that of enzymatic activity, providing strong evidence that the catalytic reaction of oxalate decarboxylase is driven by Mn(III), which is generated in the presence of dioxygen.

Polyoxovanadate-alkoxide clusters as multi-electron charge carriers for symmetric non-aqueous redox flow batteries.

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VanGelder, L E; Kosswattaarachchi, A M; Forrestel, P L; Cook, T R; Matson, E M

2018-02-14

Non-aqueous redox flow batteries have emerged as promising systems for large-capacity, reversible energy storage, capable of meeting the variable demands of the electrical grid. Here, we investigate the potential for a series of Lindqvist polyoxovanadate-alkoxide (POV-alkoxide) clusters, [V 6 O 7 (OR) 12 ] (R = CH 3 , C 2 H 5 ), to serve as the electroactive species for a symmetric, non-aqueous redox flow battery. We demonstrate that the physical and electrochemical properties of these POV-alkoxides make them suitable for applications in redox flow batteries, as well as the ability for ligand modification at the bridging alkoxide moieties to yield significant improvements in cluster stability during charge-discharge cycling. Indeed, the metal-oxide core remains intact upon deep charge-discharge cycling, enabling extremely high coulombic efficiencies (∼97%) with minimal overpotential losses (∼0.3 V). Furthermore, the bulky POV-alkoxide demonstrates significant resistance to deleterious crossover, which will lead to improved lifetime and efficiency in a redox flow battery.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

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Jung Hyun Park

2017-01-01

Full Text Available Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2 regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA- transfected Lewis lung carcinoma (LLC cells and idh2-deficient (idh2−/− mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2−/− mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration.

Science.gov (United States)

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP + -dependent isocitrate dehydrogenase ( idh2 ) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and idh2 -deficient ( idh2 -/- ) mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2 -/- mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

The redox reaction kinetics of Sinai ore for chemical looping combustion applications

International Nuclear Information System (INIS)

Ksepko, Ewelina; Babiński, Piotr; Nalbandian, Lori

2017-01-01

Highlights: • Redox reaction kinetics of Fe-Mn-rich Sinai ore was determined by TGA. • The most suitable model for reduction was D3, while R3 for oxidation. • Activation energies 35.3 and 16.70 kJ/mole were determined for reduction and oxidation. • Repetitive redox reactions favor the formation of spinel phases in Sinai ore. • Multiple redox cycles induce formation of extensive porosity of the particles. - Abstract: The objective of this work was to study the use of Sinai ore, a Fe–Mn-based ore from Egypt, as a low-cost oxygen carrier (OC) in Chemical Looping Combustion (CLC). The Sinai ore was selected because it possesses relatively high amounts of iron and manganese oxides. Furthermore, those oxides have low cost, very favorable environmental and thermodynamic properties for the CLC process. The performance of the Sinai ore as an OC in CLC was compared to that of ilmenite (Norway Tellnes mine), the most extensively studied naturally occurring Fe-based mineral. The kinetics of the reduction and oxidation reactions with the two minerals were studied using a thermogravimetric analyzer (TGA). Experiments were conducted under isothermal conditions, with multiple redox cycles, at temperatures between 750 and 950 °C. For the reduction and oxidation reactions, different concentrations of CH_4 (10–25 vol.%) and O_2 (5–20 vol.%) were applied, respectively. The kinetic parameters, such as the activation energy (E_a), pre-exponential factor (A_0), and reaction order (n), were determined for the redox reactions. Furthermore, models of the redox reactions were selected by means of a model-fitting method. For the Sinai ore, the D3 model (3-dimensional diffusion) was suitable for modeling reduction reaction kinetics. The calculated E_a was 35.3 kJ/mole, and the reaction order was determined to be approximately 0.76. The best fit for the oxidation reaction was obtained for the R3 model (shrinking core). The oxidation (regeneration) reaction E_a was equal to 16

Changes of reduced glutathion, glutathion reductase, and glutathione peroxidase after radiation in guinea pigs

International Nuclear Information System (INIS)

Erden, M.; Bor, N.M.

1984-01-01

In this series of experiments the protective action of reduced glutathion due to ionizing radiation has been studied. In the experimental group 18 guinea pigs were exposed to successive radiations of 150 rad 3 or 4 days apart. Total dose given amounted to 750 rad which is the LD50 for guinea pigs. Blood samples were taken 30 min after each exposure. The control series were sham radiated but otherwise treated identically. The cells of the removed blood samples were separated by centrifugation and were subjected to the reduced glutathion stability test. GSSGR, GPer, and LDH enzyme activities were also measured of which the latter served as a marked enzyme. It was found that LDH did not show any alteration after radiation. The reduced glutathion stability test showed a consistent but minor reduction (P greater than 0.05), in the experimental group. GSSGR enzyme activity on the other hand was reduced significantly (from 176.48 +/- 11.32 to 41.34 +/- 1.17 IU/ml of packed erythrocytes, P less than 0.001) in the same group. GPer activity showed a consistent but minor elevation during the early phase of the experimental group. It was later increased significantly beginning after 600 rad total radiation on the fourth session (P less than 0.050)

A biomimetic high-capacity phenazine-based anolyte for aqueous organic redox flow batteries

Science.gov (United States)

Hollas, Aaron; Wei, Xiaoliang; Murugesan, Vijayakumar; Nie, Zimin; Li, Bin; Reed, David; Liu, Jun; Sprenkle, Vincent; Wang, Wei

2018-06-01

Aqueous soluble organic (ASO) redox-active materials have recently attracted significant attention as alternatives to traditional transition metal ions in redox flow batteries (RFB). However, reported reversible capacities of ASO are often substantially lower than their theoretical values based on the reported maximum solubilities. Here, we describe a phenazine-based ASO compound with an exceptionally high reversible capacity that exceeds 90% of its theoretical value. By strategically modifying the phenazine molecular structure, we demonstrate an increased solubility from near-zero with pristine phenazine to as much as 1.8 M while also shifting its redox potential by more than 400 mV. An RFB based on a phenazine derivative (7,8-dihydroxyphenazine-2-sulfonic acid) at its near-saturation concentration exhibits an operating voltage of 1.4 V with a reversible anolyte capacity of 67 Ah l-1 and a capacity retention of 99.98% per cycle over 500 cycles.

The enhancement of tolerance to salt and cold stresses by modifying the redox state and salicylic acid content via the cytosolic malate dehydrogenase gene in transgenic apple plants.

Science.gov (United States)

Wang, Qing-Jie; Sun, Hong; Dong, Qing-Long; Sun, Tian-Yu; Jin, Zhong-Xin; Hao, Yu-Jin; Yao, Yu-Xin

2016-10-01

In this study, we characterized the role of an apple cytosolic malate dehydrogenase gene (MdcyMDH) in the tolerance to salt and cold stresses and investigated its regulation mechanism in stress tolerance. The MdcyMDH transcript was induced by mild cold and salt treatments, and MdcyMDH-overexpressing apple plants possessed improved cold and salt tolerance compared to wild-type (WT) plants. A digital gene expression tag profiling analysis revealed that MdcyMDH overexpression largely altered some biological processes, including hormone signal transduction, photosynthesis, citrate cycle and oxidation-reduction. Further experiments verified that MdcyMDH overexpression modified the mitochondrial and chloroplast metabolisms and elevated the level of reducing power, primarily caused by increased ascorbate and glutathione, as well as the increased ratios of ascorbate/dehydroascorbate and glutathione/glutathione disulphide, under normal and especially stress conditions. Concurrently, the transgenic plants produced a high H2 O2 content, but a low O2·- production rate was observed compared to the WT plants. On the other hand, the transgenic plants accumulated more free and total salicylic acid (SA) than the WT plants under normal and stress conditions. Taken together, MdcyMDH conferred the transgenic apple plants a higher stress tolerance by producing more reductive redox states and increasing the SA level; MdcyMDH could serve as a target gene to genetically engineer salt- and cold-tolerant trees. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Redox fronts

International Nuclear Information System (INIS)

Chapman, N.; McKinley, I.; Shea, M.; Smellie, J.

1993-01-01

This article describes the investigations of redox fronts performed at the Osamu Utsumi mine. Results obtained by modelling groups on the rate of movement of the redox fronts and on the chemical reactions involved are discussed. Some of the most important rockwater interactions which occur at redox fronts can be modelled reasonably well but the complex redox chemistry of elements like sulphur is poorly simulated. The observed enrichment of many trace elements close to the redox fronts could be of significance for high-level waste repositories, but cannot be quantified by existing models. (author) 6 figs., 1 tab

Antisense Suppression of 2-Cysteine Peroxiredoxin in Arabidopsis Specifically Enhances the Activities and Expression of Enzymes Associated with Ascorbate Metabolism But Not Glutathione Metabolism1

Science.gov (United States)

Baier, Margarete; Noctor, Graham; Foyer, Christine H.; Dietz, Karl-Josef

2000-01-01

The aim of this study was to characterize the effect of decreased 2-cysteine peroxiredoxin (2-CP) on the leaf anti-oxidative system in Arabidopsis. At three stages of leaf development, two lines of transgenic Arabidopsis mutants with decreased contents of chloroplast 2-CP were compared with wild type and a control line transformed with an empty vector. Glutathione contents and redox state were similar in all plants, and no changes in transcript levels for enzymes involved in glutathione metabolism were observed. Transcript levels for chloroplastic glutathione peroxidase were much lower than those for 2-CP, and both cytosolic and chloroplastic glutathione peroxidase were not increased in the mutants. In contrast, the foliar ascorbate pool was more oxidized in the mutants, although the difference decreased with plant age. The activities of thylakoid and stromal ascorbate peroxidase and particularly monodehydroascorbate reductase were increased as were transcripts for these enzymes. No change in dehydroascorbate reductase activity was observed, and effects on transcript abundance for glutathione reductase, catalase, and superoxide dismutase were slight or absent. The results demonstrate that 2-CP forms an integral part of the anti-oxidant network of chloroplasts and is functionally interconnected with other defense systems. Suppression of 2-CP leads to increased expression of other anti-oxidative genes possibly mediated by increased oxidation state of the leaf ascorbate pool. PMID:11027730

Electrochemical reverse engineering: A systems-level tool to probe the redox-based molecular communication of biology.

Science.gov (United States)

Li, Jinyang; Liu, Yi; Kim, Eunkyoung; March, John C; Bentley, William E; Payne, Gregory F

2017-04-01

The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology and the associated chemical dialogues occur within a context of a steep oxygen gradient that provides the driving force for a variety of reduction and oxidation (redox) reactions. While some redox couples (e.g., catecholics) can spontaneously exchange electrons, many others are kinetically "insulated" (e.g., biothiols) allowing the biology to set and control their redox states far from equilibrium. It is well known that within cells, such non-equilibrated redox couples are poised to transfer electrons to perform reactions essential to immune defense (e.g., transfer from NADH to O 2 for reactive oxygen species, ROS, generation) and protection from such oxidative stresses (e.g., glutathione-based reduction of ROS). More recently, it has been recognized that some of these redox-active species (e.g., H 2 O 2 ) cross membranes and diffuse into the extracellular environment including lumen to transmit redox information that is received by atomically-specific receptors (e.g., cysteine-based sulfur switches) that regulate biological functions. Thus, redox has emerged as an important modality in the chemical signaling that occurs in the intestine and there have been emerging efforts to develop the experimental tools needed to probe this modality. We suggest that electrochemistry provides a unique tool to experimentally probe redox interactions at a systems level. Importantly, electrochemistry offers the potential to enlist the extensive theories established in signal processing in an effort to "reverse engineer" the molecular communication occurring in this complex biological system. Here, we review our efforts to develop this

Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

Science.gov (United States)

Chausse, Bruno; Vieira-Lara, Marcel A; Sanchez, Angélica B; Medeiros, Marisa H G; Kowaltowski, Alicia J

2015-01-01

Intermittent fasting (IF) is a dietary intervention often used as an alternative to caloric restriction (CR) and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

Directory of Open Access Journals (Sweden)

Bruno Chausse

Full Text Available Intermittent fasting (IF is a dietary intervention often used as an alternative to caloric restriction (CR and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

A simple method to fabricate electrochemical sensor systems with predictable high-redox amplification

NARCIS (Netherlands)

Straver, M.G.; Odijk, Mathieu; Olthuis, Wouter; van den Berg, Albert

2012-01-01

In this paper an easy to fabricate SU8/glass-based microfluidic sensor is described with two closely spaced parallel electrodes for highly selective measurements using the redox cycling effect. By varying the length of the microfluidic entrance channel, a diffusion barrier is created for non-cycling

Splitting CO2 with a ceria‐based redox cycle in a solar‐driven thermogravimetric analyzer

Science.gov (United States)

Takacs, M.; Ackermann, S.; Bonk, A.; Neises‐von Puttkamer, M.; Haueter, Ph.; Scheffe, J. R.; Vogt, U. F.

2016-01-01

Thermochemical splitting of CO2 via a ceria‐based redox cycle was performed in a solar‐driven thermogravimetric analyzer. Overall reaction rates, including heat and mass transport, were determined under concentrated irradiation mimicking realistic operation of solar reactors. Reticulated porous ceramic (RPC) structures and fibers made of undoped and Zr4+‐doped CeO2, were endothermally reduced under radiative fluxes of 1280 suns in the temperature range 1200–1950 K and subsequently re‐oxidized with CO2 at 950–1400 K. Rapid and uniform heating was observed for 8 ppi ceria RPC with mm‐sized porosity due to its low optical thickness and volumetric radiative absorption, while ceria fibers with μm‐sized porosity performed poorly due to its opacity to incident irradiation. The 10 ppi RPC exhibited higher fuel yield because of its higher sample density. Zr4+‐doped ceria showed increasing reduction extents with dopant concentration but decreasing specific CO yield due to unfavorable oxidation thermodynamics and slower kinetics. © 2016 American Institute of Chemical Engineers AIChE J, 63: 1263–1271, 2017 PMID:28405030

Splitting CO2 with a ceria-based redox cycle in a solar-driven thermogravimetric analyzer.

Science.gov (United States)

Takacs, M; Ackermann, S; Bonk, A; Neises-von Puttkamer, M; Haueter, Ph; Scheffe, J R; Vogt, U F; Steinfeld, A

2017-04-01

Thermochemical splitting of CO 2 via a ceria-based redox cycle was performed in a solar-driven thermogravimetric analyzer. Overall reaction rates, including heat and mass transport, were determined under concentrated irradiation mimicking realistic operation of solar reactors. Reticulated porous ceramic (RPC) structures and fibers made of undoped and Zr 4+ -doped CeO 2 , were endothermally reduced under radiative fluxes of 1280 suns in the temperature range 1200-1950 K and subsequently re-oxidized with CO 2 at 950-1400 K. Rapid and uniform heating was observed for 8 ppi ceria RPC with mm-sized porosity due to its low optical thickness and volumetric radiative absorption, while ceria fibers with μm-sized porosity performed poorly due to its opacity to incident irradiation. The 10 ppi RPC exhibited higher fuel yield because of its higher sample density. Zr 4+ -doped ceria showed increasing reduction extents with dopant concentration but decreasing specific CO yield due to unfavorable oxidation thermodynamics and slower kinetics. © 2016 American Institute of Chemical Engineers , 63: 1263-1271, 2017.

Fundamentally Addressing Bromine Storage through Reversible Solid-State Confinement in Porous Carbon Electrodes: Design of a High-Performance Dual-Redox Electrochemical Capacitor.

Science.gov (United States)

Yoo, Seung Joon; Evanko, Brian; Wang, Xingfeng; Romelczyk, Monica; Taylor, Aidan; Ji, Xiulei; Boettcher, Shannon W; Stucky, Galen D

2017-07-26

Research in electric double-layer capacitors (EDLCs) and rechargeable batteries is converging to target systems that have battery-level energy density and capacitor-level cycling stability and power density. This research direction has been facilitated by the use of redox-active electrolytes that add faradaic charge storage to increase energy density of the EDLCs. Aqueous redox-enhanced electrochemical capacitors (redox ECs) have, however, performed poorly due to cross-diffusion of soluble redox couples, reduced cycle life, and low operating voltages. In this manuscript, we propose that these challenges can be simultaneously met by mechanistically designing a liquid-to-solid phase transition of oxidized catholyte (or reduced anolyte) with confinement in the pores of electrodes. Here we demonstrate the realization of this approach with the use of bromide catholyte and tetrabutylammonium cation that induces reversible solid-state complexation of Br 2 /Br 3 - . This mechanism solves the inherent cross-diffusion issue of redox ECs and has the added benefit of greatly stabilizing the reactive bromine generated during charging. Based on this new mechanistic insight on the utilization of solid-state bromine storage in redox ECs, we developed a dual-redox EC consisting of a bromide catholyte and an ethyl viologen anolyte with the addition of tetrabutylammonium bromide. In comparison to aqueous and organic electric double-layer capacitors, this system enhances energy by factors of ca. 11 and 3.5, respectively, with a specific energy of ∼64 W·h/kg at 1 A/g, a maximum power density >3 kW/kg, and cycling stability over 7000 cycles.

Transient light-induced intracellular oxidation revealed by redox biosensor

Energy Technology Data Exchange (ETDEWEB)

Kolossov, Vladimir L., E-mail: viadimer@illinois.edu [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Beaudoin, Jessica N. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Hanafin, William P. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); DiLiberto, Stephen J. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Kenis, Paul J.A. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801 (United States); Rex Gaskins, H. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Avenue, Urbana, IL 61801 (United States); Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 905 S. Goodwin Avenue, Urbana, IL 61801 (United States)

2013-10-04

Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition.

Transient light-induced intracellular oxidation revealed by redox biosensor

International Nuclear Information System (INIS)

Kolossov, Vladimir L.; Beaudoin, Jessica N.; Hanafin, William P.; DiLiberto, Stephen J.; Kenis, Paul J.A.; Rex Gaskins, H.

2013-01-01

Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition

Redox properties of iron-bearing clays and MX-80 bentonite – Electrochemical and spectroscopic characterization

International Nuclear Information System (INIS)

Hofstetter, Th. B.; Sosedova, Y.; Gorski, C.; Voegelin, A.; Sander, M.

2014-03-01

The characterization of the redox properties of Fe-bearing minerals in the presence and absence of dissolved Fe"2"+ is of major relevance for the assessment of redox reactions in natural and engineered environments such as radioactive waste repositories. In this study, we developed an electrochemical approach based on the use of soluble organic electron transfer mediators, which enabled us to quantify the redox properties of Fe-bearing clay minerals, MX- 80 bentonite and combinations of clay minerals, Fe oxides and dissolved Fe"2"+. Using mediated electrochemical oxidation and reduction, we quantified the electron accepting and donating capacities of ferrous smectite SWa-1, Wyoming montmorillonite SWy-2 and MX-80 bentonite at pH 7.5. All structural Fe in clay minerals was redox-active in contrast to that present in other, not further defined phases of MX-80. The materials investigated were redoxactive over a very wide range of Eh-values, that is the Fe"2"+/Fe_t_o_t_a_l ratio of the minerals changed from 0 to 100 % between +600 and -600 mV (vs. SHE). Redox properties were highly path-dependent due to structural changes of the minerals as revealed from the study of native and redox-cycled clay minerals after repeated reduction and re-oxidation cycles. Irreversible alteration of the mineral structure, however, was less obvious for materials with lower total Fe content such as MX-80 bentonite and SWy-2. Systems containing native montmorillonites (SWy-2 or MX-80), goethite and dissolved Fe"2"+ were also able to buffer the reduction potential E_H between 0 and -300 mV. Regardless of their Fe oxidation state, Fe-bearing minerals are redox-active over a wide potential range and therefore very relevant as redox buffers determining the fate of redox-active radionuclides and metals in waste repositories. (authors)

Redox properties of iron-bearing clays and MX-80 bentonite – Electrochemical and spectroscopic characterization

Energy Technology Data Exchange (ETDEWEB)

Hofstetter, Th. B.; Sosedova, Y.; Gorski, C.; Voegelin, A.; Sander, M.

2014-03-15

The characterization of the redox properties of Fe-bearing minerals in the presence and absence of dissolved Fe{sup 2+} is of major relevance for the assessment of redox reactions in natural and engineered environments such as radioactive waste repositories. In this study, we developed an electrochemical approach based on the use of soluble organic electron transfer mediators, which enabled us to quantify the redox properties of Fe-bearing clay minerals, MX- 80 bentonite and combinations of clay minerals, Fe oxides and dissolved Fe{sup 2+}. Using mediated electrochemical oxidation and reduction, we quantified the electron accepting and donating capacities of ferrous smectite SWa-1, Wyoming montmorillonite SWy-2 and MX-80 bentonite at pH 7.5. All structural Fe in clay minerals was redox-active in contrast to that present in other, not further defined phases of MX-80. The materials investigated were redoxactive over a very wide range of Eh-values, that is the Fe{sup 2+}/Fe{sub total} ratio of the minerals changed from 0 to 100 % between +600 and -600 mV (vs. SHE). Redox properties were highly path-dependent due to structural changes of the minerals as revealed from the study of native and redox-cycled clay minerals after repeated reduction and re-oxidation cycles. Irreversible alteration of the mineral structure, however, was less obvious for materials with lower total Fe content such as MX-80 bentonite and SWy-2. Systems containing native montmorillonites (SWy-2 or MX-80), goethite and dissolved Fe{sup 2+} were also able to buffer the reduction potential E{sub H} between 0 and -300 mV. Regardless of their Fe oxidation state, Fe-bearing minerals are redox-active over a wide potential range and therefore very relevant as redox buffers determining the fate of redox-active radionuclides and metals in waste repositories. (authors)

Redox electrodes comprised of polymer-modified carbon nanomaterials

Science.gov (United States)

Roberts, Mark; Emmett, Robert; Karakaya, Mehmet; Podila, Ramakrishna; Rao, Apparao; Clemson Physics Team; Clemson Chemical Engineering Team

2013-03-01

A shift in how we generate and use electricity requires new energy storage materials and systems compatible with hybrid electric transportation and the integration of renewable energy sources. Supercapacitors provide a solution to these needs by combining the high power, rapid switching, and exceptional cycle life of a capacitor with the high energy density of a battery. Our research brings together nanotechnology and materials chemistry to address the limitations of electrode materials. Paper electrodes fabricated with various forms of carbon nanomaterials, such as nanotubes, are modified with redox-polymers to increase the electrode's energy density while maintaining rapid discharge rates. In these systems, the carbon nanomaterials provide the high surface area, electrical conductivity, nanoscale and porosity, while the redox polymers provide a mechanism for charge storage through Faradaic charge transfer. The design of redox polymers and their incorporation into nanomaterial electrodes will be discussed with a focus on enabling high power and high energy density electrodes.

Anti-inflammatory polymersomes of redox-responsive polyprodrug amphiphiles with inflammation-triggered indomethacin release characteristics.

Science.gov (United States)

Tan, Jiajia; Deng, Zhengyu; Liu, Guhuan; Hu, Jinming; Liu, Shiyong

2018-03-21

Inflammation serves as a natural defense mechanism to protect living organisms from infectious diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) can help relieve inflammatory reactions and are clinically used to treat pain, fever, and inflammation, whereas long-term use of NSAIDs may lead to severe side effects including gastrointestinal damage and cardiovascular toxicity. Therefore, it is of increasing importance to configure new dosing strategies and alleviate the side effects of NSAIDs. Towards this goal, glutathione (GSH)-responsive disulfide bonds and hydrogen peroxide (H 2 O 2 )-reactive phenylboronic ester linkages were utilized as triggering moieties in this work to design redox-responsive prodrug monomers and polyprodrug amphiphiles based on indomethacin (IND) drug. Note that IND is a widely prescribed NSAID in the clinic. Starting from three types of redox-reactive IND prodrug monomers, redox-responsive polyprodrug amphiphiles were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerizations of prodrug monomers using poly(ethylene oxide) (PEO)-based macroRAFT agent. The resultant polyprodrug amphiphiles with high IND loading contents (>33 wt%) could self-assemble into polymersomes with PEO shielding coronas and redox-responsive bilayer membranes composed of IND prodrugs. Upon incubation with GSH or H 2 O 2 , controlled release of intact IND in the active form from polyprodrug polymersomes was actuated by GSH-mediated disulfide cleavage reaction and H 2 O 2 -mediated oxidation of phenylboronic ester moieties, respectively, followed by self-immolative degradation events. Furthermore, in vitro studies at the cellular level revealed that redox-responsive polymersomes could efficiently relieve inflammatory responses induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. Copyright © 2018. Published by Elsevier Ltd.

A Lipid Transfer Protein Increases the Glutathione Content and Enhances Arabidopsis Resistance to a Trichothecene Mycotoxin.

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John E McLaughlin

Full Text Available Fusarium head blight (FHB or scab is one of the most important plant diseases worldwide, affecting wheat, barley and other small grains. Trichothecene mycotoxins such as deoxynivalenol (DON accumulate in the grain, presenting a food safety risk and health hazard to humans and animals. Despite considerable breeding efforts, highly resistant wheat or barley cultivars are not available. We screened an activation tagged Arabidopsis thaliana population for resistance to trichothecin (Tcin, a type B trichothecene in the same class as DON. Here we show that one of the resistant lines identified, trichothecene resistant 1 (trr1 contains a T-DNA insertion upstream of two nonspecific lipid transfer protein (nsLTP genes, AtLTP4.4 and AtLTP4.5. Expression of both nsLTP genes was induced in trr1 over 10-fold relative to wild type. Overexpression of AtLTP4.4 provided greater resistance to Tcin than AtLTP4.5 in Arabidopsis thaliana and in Saccharomyces cerevisiae relative to wild type or vector transformed lines, suggesting a conserved protection mechanism. Tcin treatment increased reactive oxygen species (ROS production in Arabidopsis and ROS stain was associated with the chloroplast, the cell wall and the apoplast. ROS levels were attenuated in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls. Exogenous addition of glutathione and other antioxidants enhanced resistance of Arabidopsis to Tcin while the addition of buthionine sulfoximine, an inhibitor of glutathione synthesis, increased sensitivity, suggesting that resistance was mediated by glutathione. Total glutathione content was significantly higher in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls, highlighting the importance of AtLTP4.4 in maintaining the redox state. These results demonstrate that trichothecenes cause ROS accumulation and overexpression of AtLTP4.4 protects against trichothecene-induced oxidative stress by increasing the glutathione

Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice

Directory of Open Access Journals (Sweden)

Isabela Finamor

2017-04-01

Full Text Available No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC. Chronic administration of aspartame increased plasma alanine aminotransferase (ALT and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH, oxidized glutathione (GSSG, γ-glutamylcysteine ​​(γ-GC, and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM, and S-adenosylhomocysteine ​​(SAH. Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway.

Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice.

Science.gov (United States)

Finamor, Isabela; Pérez, Salvador; Bressan, Caroline A; Brenner, Carlos E; Rius-Pérez, Sergio; Brittes, Patricia C; Cheiran, Gabriele; Rocha, Maria I; da Veiga, Marcelo; Sastre, Juan; Pavanato, Maria A

2017-04-01

No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ​​(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ​​(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway. Copyright © 2017. Published by Elsevier B.V.

A High-Current, Stable Nonaqueous Organic Redox Flow Battery

Energy Technology Data Exchange (ETDEWEB)

Wei, Xiaoliang; Duan, Wentao; Huang, Jinhua; Zhang, Lu; Li, Bin; Reed, David; Xu, Wu; Sprenkle, Vincent; Wang, Wei

2016-10-14

Nonaqueous redox flow batteries are promising in pursuit of high-energy storage systems owing to the broad voltage window, but currently are facing key challenges such as poor cycling stability and lack of suitable membranes. Here we report a new nonaqueous all-organic flow chemistry that demonstrates an outstanding cell cycling stability primarily because of high chemical persistency of the organic radical redox species and their good compatibility with the supporting electrolyte. A feasibility study shows that Daramic® and Celgard® porous separators can lead to high cell conductivity in flow cells thus producing remarkable cell efficiency and material utilization even at high current operations. This result suggests that the thickness and pore size are the key performance-determining factors for porous separators. With the greatly improved flow cell performance, this new flow system largely addresses the above mentioned challenges and the findings may greatly expedite the development of durable nonaqueous flow batteries.

Redox behaviors of iron by absorption spectroscopy and redox potential measurement

International Nuclear Information System (INIS)

Oh, Jae Yong

2010-02-01

This work is performed to study the redox (reduction/oxidation) behaviors of iron in aqueous system by a combination of absorption spectroscopy and redox potential measurements. There are many doubts on redox potential measurements generally showing low accuracies and high uncertainties. In the present study, redox potentials are measured by utilizing various redox electrodes such as Pt, Au, Ag, and glassy carbon (GC) electrodes. Measured redox potentials are compared with calculated redox potentials based on the chemical oxidation speciation of iron and thermodynamic data by absorption spectroscopy, which provides one of the sensitive and selective spectroscopic methods for the chemical speciation of Fe(II/III). From the comparison analyses, redox potential values measured by the Ag redox electrode are fairly consistent with those calculated by the chemical aqueous speciation of iron in the whole system. In summary, the uncertainties of measured redox potentials are closely related with the total Fe concentration and affected by the formation of mixed potentials due to Fe(III) precipitates in the pH range of 6 ∼ 9 beyond the solubility of Fe(III), whilst being independent of the initially prepared concentration ratios between Fe(II) and Fe(III)

Electrochemical redox processes involving soluble cerium species

International Nuclear Information System (INIS)

Arenas, L.F.; Ponce de León, C.; Walsh, F.C.

2016-01-01

Highlights: • The relevance of cerium in laboratory and industrial electrochemistry is considered. • The history of fundamental electrochemical studies and applications is considered. • The chemistry, redox thermodynamics and electrode kinetics of cerium are summarised. • The uses of cerium ions in synthesis, energy storage, analysis and environmental treatment are illustrated. • Research needs and development perspectives are discussed. - Abstract: Anodic oxidation of cerous ions and cathodic reduction of ceric ions, in aqueous acidic solutions, play an important role in electrochemical processes at laboratory and industrial scale. Ceric ions, which have been used for oxidation of organic wastes and off-gases in environmental treatment, are a well-established oxidant for indirect organic synthesis and specialised cleaning processes, including oxide film removal from tanks and process pipework in nuclear decontamination. They also provide a classical reagent for chemical analysis in the laboratory. The reversible oxidation of cerous ions is an important reaction in the positive compartment of various redox flow batteries during charge and discharge cycling. A knowledge of the thermodynamics and kinetics of the redox reaction is critical to an understanding of the role of cerium redox species in these applications. Suitable choices of electrode material (metal or ceramic; coated or uncoated), geometry/structure (2-or 3-dimensional) and electrolyte flow conditions (hence an acceptable mass transport rate) are critical to achieving effective electrocatalysis, a high performance and a long lifetime. This review considers the electrochemistry of soluble cerium species and their diverse uses in electrochemical technology, especially for redox flow batteries and mediated electrochemical oxidation.

Subcellular distribution of glutathione and cysteine in cyanobacteria.

Science.gov (United States)

Zechmann, Bernd; Tomasić, Ana; Horvat, Lucija; Fulgosi, Hrvoje

2010-10-01

Glutathione plays numerous important functions in eukaryotic and prokaryotic cells. Whereas it can be found in virtually all eukaryotic cells, its production in prokaryotes is restricted to cyanobacteria and proteobacteria and a few strains of gram-positive bacteria. In bacteria, it is involved in the protection against reactive oxygen species (ROS), osmotic shock, acidic conditions, toxic chemicals, and heavy metals. Glutathione synthesis in bacteria takes place in two steps out of cysteine, glutamate, and glycine. Cysteine is the limiting factor for glutathione biosynthesis which can be especially crucial for cyanobacteria, which rely on both the sufficient sulfur supply from the growth media and on the protection of glutathione against ROS that are produced during photosynthesis. In this study, we report a method that allows detection and visualization of the subcellular distribution of glutathione in Synechocystis sp. This method is based on immunogold cytochemistry with glutathione and cysteine antisera and computer-supported transmission electron microscopy. Labeling of glutathione and cysteine was restricted to the cytosol and interthylakoidal spaces. Glutathione and cysteine could not be detected in carboxysomes, cyanophycin granules, cell walls, intrathylakoidal spaces, periplasm, and vacuoles. The accuracy of the glutathione and cysteine labeling is supported by two observations. First, preadsorption of the antiglutathione and anticysteine antisera with glutathione and cysteine, respectively, reduced the density of the gold particles to background levels. Second, labeling of glutathione and cysteine was strongly decreased by 98.5% and 100%, respectively, in Synechocystis sp. cells grown on media without sulfur. This study indicates a strong similarity of the subcellular distribution of glutathione and cysteine in cyanobacteria and plastids of plants and provides a deeper insight into glutathione metabolism in bacteria.

A comparative study of all-vanadium and iron-chromium redox flow batteries for large-scale energy storage

Science.gov (United States)

Zeng, Y. K.; Zhao, T. S.; An, L.; Zhou, X. L.; Wei, L.

2015-12-01

The promise of redox flow batteries (RFBs) utilizing soluble redox couples, such as all vanadium ions as well as iron and chromium ions, is becoming increasingly recognized for large-scale energy storage of renewables such as wind and solar, owing to their unique advantages including scalability, intrinsic safety, and long cycle life. An ongoing question associated with these two RFBs is determining whether the vanadium redox flow battery (VRFB) or iron-chromium redox flow battery (ICRFB) is more suitable and competitive for large-scale energy storage. To address this concern, a comparative study has been conducted for the two types of battery based on their charge-discharge performance, cycle performance, and capital cost. It is found that: i) the two batteries have similar energy efficiencies at high current densities; ii) the ICRFB exhibits a higher capacity decay rate than does the VRFB; and iii) the ICRFB is much less expensive in capital costs when operated at high power densities or at large capacities.

Redox regulation of calcium release in skeletal and cardiac muscle

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CECILIA HIDALGO

2002-01-01

Full Text Available In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist and Mg2+ (endogenous inhibitor on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 µM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 µM [Ca2+]. In 10 µM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] ­ 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 µM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discussed

Redox-based epigenetic status in drug addiction: a potential contributor to gene priming and a mechanistic rationale for metabolic intervention.

Science.gov (United States)

Trivedi, Malav S; Deth, Richard

2014-01-01

Alcohol and other drugs of abuse, including psychostimulants and opioids, can induce epigenetic changes: a contributing factor for drug addiction, tolerance, and associated withdrawal symptoms. DNA methylation is a major epigenetic mechanism and it is one of more than 200 methylation reactions supported by methyl donor S-adenosylmethionine (SAM). Levels of SAM are controlled by cellular redox status via the folate and vitamin B12-dependent enzyme methionine synthase (MS). For example, under oxidative conditions MS is inhibited, diverting its substrate homocysteine (HCY) to the trans sulfuration pathway. Alcohol, dopamine, and morphine, can alter intracellular levels of glutathione (GSH)-based cellular redox status, subsequently affecting SAM levels and DNA methylation status. Here, existing evidence is presented in a coherent manner to propose a novel hypothesis implicating the involvement of redox-based epigenetic changes in drug addiction. Further, we discuss how a "gene priming" phenomenon can contribute to the maintenance of redox and methylation status homeostasis under various stimuli including drugs of abuse. Additionally, a new mechanistic rationale for the use of metabolic interventions/redox-replenishers as symptomatic treatment of alcohol and other drug addiction and associated withdrawal symptoms is also provided. Hence, the current review article strengthens the hypothesis that neuronal metabolism has a critical bidirectional coupling with epigenetic changes in drug addiction exemplified by the link between redox-based metabolic changes and resultant epigenetic consequences under the effect of drugs of abuse.

A regulatory review for products containing glutathione

Directory of Open Access Journals (Sweden)

Nur Hidayah Abd Rahim

2016-01-01

Full Text Available Glutathione is a potent antioxidant as well as has important role for DNA synthesis and repair, protein synthesis, amino acid transport, and enzyme activation. Besides this, Glutathione products are now mainly selling as whitening agent which are mainly marketing through social media (Facebook and different websites. Information is not available whether glutathione product are following the regulatory guidelines of National Pharmaceutical Control Bureau of Malaysia (NPCB for selling, advertisement and promotion. This review was carried out by extracting information about glutathione from scientific database using PubMed, Cochrane Library and Embase. Analysis of the available information, case example of glutathione products showed that a brand of glutathione (Glutacaps HQ did not show the product's registration number from NPCB, and also did not show the name, address, contact number of the advertiser, and even not found the name of the manufacture. Without providing the above mentioned information, the product is selling and promoting through social media (fb which is not allowed by the NPCB guidelines part 4.14. So far, only two clinical trials were conducted on glutathione supplementation for 4 weeks duration. There was no serious or systematic adverse effects reported in clinical trials. As the two clinic trials resulted contradictory outcomes, further studies needed for conformation of the clinic benefits of glutathione. Otherwise, random use of glutathione may be risk for the health of the people. Besides, the marketer mainly promoting glutathione as the skin whitening beauty product instead of using as health supplement, it may cause additional and serious risk to the users as the manufacturer not providing sufficient information about the product, its registration number, manufacturing company, etc.

Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons.

Science.gov (United States)

Ghosh, Debolina; Levault, Kelsey R; Brewer, Gregory J

2014-08-01

Aging, a major risk factor in Alzheimer's disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance. Neurons stressed by either depleting NAD(P)H or GSH indicated that NADH redox control is upstream of GSH levels. Further, although depletion of NAD(P)H or GSH correlated linearly with neuron death, compared with GSH depletion, higher neurodegeneration was observed when NAD(P)H was extrapolated to zero, especially in old age, and in the 3xTg-AD neurons. We also observed an age-dependent loss of gene expression of key redox-dependent biosynthetic enzymes, NAMPT (nicotinamide phosphoribosyltransferase), and NNT (nicotinamide nucleotide transhydrogenase). Moreover, age-related correlations between brain NNT or NAMPT gene expression and NADPH levels suggest that these genes contribute to the age-related declines in NAD(P)H. Our data indicate that in aging and more so in AD-like neurons, NAD(P)H redox control is upstream of GSH and an oxidative redox shift that promotes neurodegeneration. Thus, NAD(P)H generation may be a more efficacious therapeutic target upstream of GSH and ROS. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Plant redox proteomics

DEFF Research Database (Denmark)

Navrot, Nicolas; Finnie, Christine; Svensson, Birte

2011-01-01

PTMs in regulating enzymatic activities and controlling biological processes in plants. Notably, proteins controlling the cellular redox state, e.g. thioredoxin and glutaredoxin, appear to play dual roles to maintain oxidative stress resistance and regulate signal transduction pathways via redox PTMs......In common with other aerobic organisms, plants are exposed to reactive oxygen species resulting in formation of post-translational modifications related to protein oxidoreduction (redox PTMs) that may inflict oxidative protein damage. Accumulating evidence also underscores the importance of redox....... To get a comprehensive overview of these types of redox-regulated pathways there is therefore an emerging interest to monitor changes in redox PTMs on a proteome scale. Compared to some other PTMs, e.g. protein phosphorylation, redox PTMs have received less attention in plant proteome analysis, possibly...

Effect of (--∆9-tetrahydrocannabinoid on the hepatic redox state of mice

Directory of Open Access Journals (Sweden)

C.E. Pinto

2010-04-01

Full Text Available (--∆9-Tetrahydrocannabinol (∆9-THC, a psychoactive component of marijuana, has been reported to induce oxidative damage in vivo and in vitro. In this study, we administered ∆9-THC to healthy C57BL/6J mice aged 15 weeks in order to determine its effect on hepatic redox state. Mice were divided into 3 groups: ∆9-THC (N = 10, treated with 10 mg/kg body weight ∆9-THC daily; VCtrl (N = 10, treated with vehicle [1:1:18, cremophor EL® (polyoxyl 35 castor oil/ethanol/saline]; Ctrl (N = 10, treated with saline. Animals were injected ip twice a day with 5 mg/kg body weight for 10 days. Lipid peroxidation, protein carbonylation and DNA oxidation were used as biomarkers of oxidative stress. The endogenous antioxidant defenses analyzed were glutathione (GSH levels as well as enzyme activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase, and glutathione peroxidase (GPx in liver homogenates. The levels of mRNA of the cannabinoid receptors CB1 and CB2 were also monitored. Treatment with ∆9-THC did not produce significant changes in oxidative stress markers or in mRNA levels of CB1 and CB2 receptors in the liver of mice, but attenuated the increase in the selenium-dependent GPx activity (Δ9-THC: 8%; VCtrl: 23% increase and the GSH/oxidized GSH ratio (Δ9-THC: 61%; VCtrl: 96% increase, caused by treatment with the vehicle. Δ9-THC administration did not show any harmful effects on lipid peroxidation, protein carboxylation or DNA oxidation in the healthy liver of mice but attenuated unexpected effects produced by the vehicle containing ethanol/cremophor EL®.

Redox activity of airborne particulate matter at different sites in the Los Angeles Basin

International Nuclear Information System (INIS)

Cho, Arthur K.; Sioutas, Constantinos; Miguel, Antonio H.; Kumagai, Yoshito; Schmitz, Debra A.; Singh, Manisha; Eiguren-Fernandez, Arantza; Froines, John R.

2005-01-01

intracellular glutathione, which has relevance to induction of oxidative stress. Comparison of the redox activity with chemical composition showed a reasonable correlation of redox activity with elemental carbon (r 2 =0.79), organic carbon (r 2 =0.53), and with benzo[ghi]perylene (r 2 =0.82), consistent with species typically found in mobile emission sources

Tumor suppressor function of the plasma glutathione peroxidase Gpx3 in colitis-associated carcinoma

Science.gov (United States)

Barrett, Caitlyn W.; Ning, Wei; Chen, Xi; Smith, J. Joshua; Washington, Mary K; Hill, Kristina E.; Coburn, Lori A.; Peek, Richard M.; Chaturvedi, Rupesh; Wilson, Keith T.; Burk, Raymond F.; Williams, Christopher S.

2012-01-01

The glutathione peroxidases, a family of selenocysteine-containing redox enzymes, play pivotal roles in balancing the signaling, immunomodulatory and deleterious effects of reactive oxygen species (ROS). The glutathione peroxidase GPX3 is the only extracellular member of this family, suggesting it may defend cells against ROS in the extracellular environment. Notably, GPX3 hypermethylation and underexpression occurs commonly in prostate, gastric, cervical, thyroid and colon cancers. We took a reverse genetics approach to investigate whether GPX3 would augment inflammatory colonic tumorigenesis, a process characterized by oxidative stress and inflammation, comparing Gpx3−/− mice established two-stage model of inflammatory colon carcinogenesis. Gpx3-deficient mice exhibited an increased tumor number, though not size, along with a higher degree of dysplasia. Additionally, they exhibited increased inflammation with redistribution towards pro-tumorigenic M2 macrophage subsets, increased proliferation, hyperactive WNT signaling, and increased DNA damage. To determine the impact of acute gene loss in an established colon cancer line, we silenced GPX3 in human Caco2 cells, resulting in increased ROS production, DNA damage and apoptosis in response to oxidative stress, combined with decreased contact-independent growth. Taken together, our results suggested an immunomodulatory role for GPX3 that limits the development of colitis-associated carcinoma. PMID:23221387

Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway.

Science.gov (United States)

Hatori, Yuta; Yan, Ye; Schmidt, Katharina; Furukawa, Eri; Hasan, Nesrin M; Yang, Nan; Liu, Chin-Nung; Sockanathan, Shanthini; Lutsenko, Svetlana

2016-02-16

Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transition from a broad range of redox states to a uniformly reducing cytosol facilitates reduction of the copper chaperone Atox1, liberating its metal-binding site. Concomitantly, expression of Atox1 and its partner, a copper transporter ATP7A, is upregulated. These events produce a higher flux of copper through the secretory pathway that balances copper in the cytosol and increases supply of the cofactor to copper-dependent enzymes, expression of which is elevated in differentiated neurons. Direct link between glutathione oxidation and copper compartmentalization allows for rapid metabolic adjustments essential for normal neuronal function.

Facile approach to prepare pH and redox-responsive nanogels via Diels-Alder click reaction

Directory of Open Access Journals (Sweden)

C. M. Q. Le

2018-08-01

Full Text Available A novel pH and redox responsive system of sub-100 nm nanogels was prepared by arm-first approach via Diels-Alder click reaction. First, well-defined poly(ethylene glycol-block-poly(styrene-alt-maleic anhydride (PEG-b-PSM was synthesized and subsequently functionalized with furfuryl amine, leading to the formation of the dual-functional block copolymer of PEG-b-PSMf. The furfuryl groups in the PSMf block were employed to incorporate a redox-responsive linkage and the carboxylic acid moieties generated through functionalization acted as a pH-responsive part. The Diels-Alder click reaction between a bismaleimide crosslinker and PEG-b-PSMf was conducted at 60 °C, affording star-like nanogel structures. Doxorubicin, a model anticancer drug, was loaded into to the core of the nanogels primarily by the ionic interaction with carboxylates of core blocks and a highest drug loading capacity of 38.1% was obtained. Furthermore, the in vitro profile showed a low release percentage (11.2% of DOX at PBS pH 7.4, whereas a burst release (62% at pH 5.0 in the presence of 10 mM glutathione, indicating the effective pH and redox responsive characteristic of the PEG-b-PSMf nanogels.

Characterization of PEDOT-Quinone Conducting Redox Polymers for Water Based Secondary Batteries

International Nuclear Information System (INIS)

Sterby, Mia; Emanuelsson, Rikard; Huang, Xiao; Gogoll, Adolf; Strømme, Maria; Sjödin, Martin

2017-01-01

Lithium-ion technologies show great promise to meet the demands that the transition towards renewable energy sources and the electrification of the transport sector put forward. However, concerns regarding lithium-ion batteries, including limited material resources, high energy consumption during production, and flammable electrolytes, necessitate research on alternative technologies for electrochemical energy storage. Organic materials derived from abundant building blocks and with tunable properties, together with water based electrolytes, could provide safe, inexpensive and sustainable alternatives. In this study, two conducting redox polymers based on poly(3,4-ethylenedioxythiophene) (PEDOT) and a hydroquinone pendant group have been synthesized and characterized in an acidic aqueous electrolyte. The polymers were characterized with regards to kinetics, pH dependence, and mass changes during oxidation and reduction, as well as their conductance. Both polymers show redox matching, i.e. the quinone redox reaction occurs within the potential region where the polymer is conducting, and fast redox conversion that involves proton cycling during pendant group redox conversion. These properties make the presented materials promising candidates as electrode materials for water based all-organic batteries.

Reverse Engineering Applied to Red Human Hair Pheomelanin Reveals Redox-Buffering as a Pro-Oxidant Mechanism

Science.gov (United States)

Kim, Eunkyoung; Panzella, Lucia; Micillo, Raffaella; Bentley, William E.; Napolitano, Alessandra; Payne, Gregory F.

2015-01-01

Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV-independent pathway to melanoma carcinogenesis and implicated pheomelanin’s pro-oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular antioxidants. Here, we applied an electrochemically-based reverse engineering methodology to compare the redox properties of human hair pheomelanin with model synthetic pigments and natural eumelanin. This methodology exposes the insoluble melanin samples to complex potential (voltage) inputs and measures output response characteristics to assess redox activities. The results demonstrate that both eumelanin and pheomelanin are redox-active, they can rapidly (sec-min) and repeatedly redox-cycle between oxidized and reduced states, and pheomelanin possesses a more oxidative redox potential. This study suggests that pheomelanin’s redox-based pro-oxidant activity may contribute to sustaining a chronic oxidative stress condition through a redox-buffering mechanism. PMID:26669666

Geomicrobiological redox cycling of the transuranic element neptunium.

Science.gov (United States)

Law, Gareth T W; Geissler, Andrea; Lloyd, Jonathan R; Livens, Francis R; Boothman, Christopher; Begg, James D C; Denecke, Melissa A; Rothe, Jörg; Dardenne, Kathy; Burke, Ian T; Charnock, John M; Morris, Katherine

2010-12-01

Microbial processes can affect the environmental behavior of redox sensitive radionuclides, and understanding these reactions is essential for the safe management of radioactive wastes. Neptunium, an alpha-emitting transuranic element, is of particular importance because of its long half-life, high radiotoxicity, and relatively high solubility as Np(V)O(2)(+) under oxic conditions. Here, we describe experiments to explore the biogeochemistry of Np where Np(V) was added to oxic sediment microcosms with indigenous microorganisms and anaerobically incubated. Enhanced Np removal to sediments occurred during microbially mediated metal reduction, and X-ray absorption spectroscopy showed this was due to reduction to poorly soluble Np(IV) on solids. In subsequent reoxidation experiments, sediment-associated Np(IV) was somewhat resistant to oxidative remobilization. These results demonstrate the influence of microbial processes on Np solubility and highlight the critical importance of radionuclide biogeochemistry in nuclear legacy management.

The Intra- or Extracellular Redox State Was Not Affected by a High vs. Low Glycemic Response Diet in Mice

Science.gov (United States)

Kleckner, Amber S.; Wong, Siu; Corkey, Barbara E.

2015-01-01

A low glycemic response (LGR) vs. high glycemic response (HGR) diet helps curtail the development of obesity and diabetes, though the mechanisms are unknown. We hypothesized that consumption of a HGR vs. a LGR diet would lead to a more oxidized circulating redox state and predicted that a HGR diet would increase fat accumulation, reduce insulin sensitivity, and impair metabolic acclimation to a high fat diet in a mouse model. Hence, male C57BL/6 mice consumed a HGR or LGR diet for 16 weeks and a subset of the mice subsequently consumed a high fat diet for 4 weeks. We found that body mass increased at a faster rate for those consuming the HGR diet. Percent body fat was greater and percent lean mass was lesser in the HGR group starting at 12 weeks. However, the groups did not differ in terms of glucose tolerance at week 14 and metabolic parameters (respiratory exchange ratio, heat production, activity) at weeks 4 or 15. Moreover, mice on either diet did not show differences in metabolic acclimation to the high fat leg of the study. At the termination of the study, the groups did not differ in terms of redox pairs (lactate/pyruvate and β-hydroxybutyrate/acetoacetate) or thioredoxin reductase activity in blood. Also, total and oxidized glutathione levels and lipid peroxidation were similar in blood and liver. Correlations between baseline measures, longitudinal parameters, environmental conditions, and terminal metrics revealed that individual mice have innate propensities to metabolic regulation that may be difficult to perturb with diet alone; for example, starting mass correlated negatively with energy expenditure 4 weeks into the study and total hepatic glutathione at the end of the study. In conclusion, these data suggest that the mechanism by which HGR carbohydrates contributes to obesity is not via prolonged oxidation of the circulating redox state. PMID:26030878

The Intra- or Extracellular Redox State Was Not Affected by a High vs. Low Glycemic Response Diet in Mice.

Directory of Open Access Journals (Sweden)

Amber S Kleckner

Full Text Available A low glycemic response (LGR vs. high glycemic response (HGR diet helps curtail the development of obesity and diabetes, though the mechanisms are unknown. We hypothesized that consumption of a HGR vs. a LGR diet would lead to a more oxidized circulating redox state and predicted that a HGR diet would increase fat accumulation, reduce insulin sensitivity, and impair metabolic acclimation to a high fat diet in a mouse model. Hence, male C57BL/6 mice consumed a HGR or LGR diet for 16 weeks and a subset of the mice subsequently consumed a high fat diet for 4 weeks. We found that body mass increased at a faster rate for those consuming the HGR diet. Percent body fat was greater and percent lean mass was lesser in the HGR group starting at 12 weeks. However, the groups did not differ in terms of glucose tolerance at week 14 and metabolic parameters (respiratory exchange ratio, heat production, activity at weeks 4 or 15. Moreover, mice on either diet did not show differences in metabolic acclimation to the high fat leg of the study. At the termination of the study, the groups did not differ in terms of redox pairs (lactate/pyruvate and β-hydroxybutyrate/acetoacetate or thioredoxin reductase activity in blood. Also, total and oxidized glutathione levels and lipid peroxidation were similar in blood and liver. Correlations between baseline measures, longitudinal parameters, environmental conditions, and terminal metrics revealed that individual mice have innate propensities to metabolic regulation that may be difficult to perturb with diet alone; for example, starting mass correlated negatively with energy expenditure 4 weeks into the study and total hepatic glutathione at the end of the study. In conclusion, these data suggest that the mechanism by which HGR carbohydrates contributes to obesity is not via prolonged oxidation of the circulating redox state.

Involvement of human glutathione S-transferase isoenzymes in the conjugation of cyclophosphamide metabolites with glutathione

NARCIS (Netherlands)

Dirven, H.A.A.M.; Ommen, B. van; Bladeren, P.J. van

1994-01-01

Alkylating agents can be detoxified by conjugation with glutathione (GSH). One of the physiological significances of this lies in the observation that cancer cells resistant to the cytotoxic effects of alkylating agents have higher levels of GSH and high glutathione S-transferase (GST) activity.

Hydrologic control on redox and nitrogen dynamics in a peatland soil.

Science.gov (United States)

Rubol, Simonetta; Silver, Whendee L; Bellin, Alberto

2012-08-15

Soils are a dominant source of nitrous oxide (N(2)O), a potent greenhouse gas. However, the complexity of the drivers of N(2)O production and emissions has hindered our ability to predict the magnitude and spatial dynamics of N(2)O fluxes. Soil moisture can be considered a key driver because it influences oxygen (O(2)) supply, which feeds back on N(2)O sources (nitrification versus denitrification) and sinks (reduction to dinitrogen). Soil water content is directly linked to O(2) and redox potential, which regulate microbial metabolism and chemical transformations in the environment. Despite its importance, only a few laboratory studies have addressed the effects of hydrological transient dynamics on nitrogen (N) cycling in the vadose zone. To further investigate these aspects, we performed a long term experiment in a 1.5 m depth soil column supplemented by chamber experiments. With this experiment, we aimed to investigate how soil moisture dynamics influence redox sensitive N cycling in a peatland soil. As expected, increased soil moisture lowered O(2) concentrations and redox potential in the soil. The decline was more severe for prolonged saturated conditions than for short events and at deep than at the soil surface. Gaseous and dissolved N(2)O, dissolved nitrate (NO(3)(-)) and ammonium (NH(4)(+)) changed considerably along the soil column profile following trends in soil O(2) and redox potential. Hot spots of N(2)O concentrations corresponded to high variability in soil O(2) in the upper and lower parts of the column. Results from chamber experiments confirmed high NO(3)(-) reduction potential in soils, particularly from the bottom of the column. Under our experimental conditions, we identified a close coupling of soil O(2) and N(2)O dynamics, both of which lagged behind soil moisture changes. These results highlight the relationship among soil hydrologic properties, redox potential and N cycling, and suggest that models working at a daily scale need to

Chloride supporting electrolytes for all-vanadium redox flow batteries.

Science.gov (United States)

Kim, Soowhan; Vijayakumar, M; Wang, Wei; Zhang, Jianlu; Chen, Baowei; Nie, Zimin; Chen, Feng; Hu, Jianzhi; Li, Liyu; Yang, Zhenguo

2011-10-28

This paper examines vanadium chloride solutions as electrolytes for an all-vanadium redox flow battery. The chloride solutions were capable of dissolving more than 2.3 M vanadium at varied valence states and remained stable at 0-50 °C. The improved stability appeared due to the formation of a vanadium dinuclear [V(2)O(3)·4H(2)O](4+) or a dinuclear-chloro complex [V(2)O(3)Cl·3H(2)O](3+) in the solutions over a wide temperature range. The all-vanadium redox flow batteries with the chloride electrolytes demonstrated excellent reversibility and fairly high efficiencies. Only negligible, if any, gas evolution was observed. The improved energy capacity and good performance, along with the ease in heat management, would lead to substantial reduction in capital cost and life-cycle cost, making the vanadium chloride redox flow battery a promising candidate for stationary applications. This journal is © the Owner Societies 2011

Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

Science.gov (United States)

Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

2016-01-01

Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V. PMID:27966605

Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

Science.gov (United States)

Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

2016-12-01

Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V.

High-Performance Oligomeric Catholytes for Effective Macromolecular Separation in Nonaqueous Redox Flow Batteries.

Science.gov (United States)

Hendriks, Koen H; Robinson, Sophia G; Braten, Miles N; Sevov, Christo S; Helms, Brett A; Sigman, Matthew S; Minteer, Shelley D; Sanford, Melanie S

2018-02-28

Nonaqueous redox flow batteries (NRFBs) represent an attractive technology for energy storage from intermittent renewable sources. In these batteries, electrical energy is stored in and extracted from electrolyte solutions of redox-active molecules (termed catholytes and anolytes) that are passed through an electrochemical flow cell. To avoid battery self-discharge, the anolyte and catholyte solutions must be separated by a membrane in the flow cell. This membrane prevents crossover of the redox active molecules, while simultaneously allowing facile transport of charge-balancing ions. A key unmet challenge for the field is the design of redox-active molecule/membrane pairs that enable effective electrolyte separation while maintaining optimal battery properties. Herein, we demonstrate the development of oligomeric catholytes based on tris(dialkylamino)cyclopropenium (CP) salts that are specifically tailored for pairing with size-exclusion membranes composed of polymers of intrinsic microporosity (PIMs). Systematic studies were conducted to evaluate the impact of oligomer size/structure on properties that are crucial for flow battery performance, including cycling stability, charge capacity, solubility, electron transfer kinetics, and crossover rates. These studies have led to the identification of a CP-derived tetramer in which these properties are all comparable, or significantly improved, relative to the monomeric counterpart. Finally, a proof-of-concept flow battery is demonstrated by pairing this tetrameric catholyte with a PIM membrane. After 6 days of cycling, no crossover is detected, demonstrating the promise of this approach. These studies provide a template for the future design of other redox-active oligomers for this application.

New insights into redox regulation of stem cell self-renewal and differentiation.

Science.gov (United States)

Ren, Fenglian; Wang, Kui; Zhang, Tao; Jiang, Jingwen; Nice, Edouard Collins; Huang, Canhua

2015-08-01

Reactive oxygen species (ROS), the natural byproducts of aerobic metabolism, are precisely orchestrated to evoke diverse signaling pathways. To date, studies have focused mainly on the detrimental effects of ROS in stem cells. Recently, accumulating evidence has suggested that ROS also function as second messengers that modulate stem cell self-renewal and differentiation by regulating intricate signaling networks. Although many efforts have been made to clarify the general effects of ROS on signal transduction in stem cells, less is known about the initial and direct executors of ROS signaling, which are known as 'redox sensors'. Modifications of cysteine residues in redox sensors are of significant importance in the modulation of protein function in response to different redox conditions. Intriguingly, most key molecules in ROS signaling and cell cycle regulation (including transcriptional factors and kinases) that are crucial in the regulation of stem cell self-renewal and differentiation have the potential to be redox sensors. We highlight herein the importance of redox regulation of these key regulators in stem cell self-renewal and differentiation. Understanding the mechanisms of redox regulation in stem cell self-renewal and differentiation will open exciting new perspectives for stem cell biology. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53.

Science.gov (United States)

Riscal, Romain; Schrepfer, Emilie; Arena, Giuseppe; Cissé, Madi Y; Bellvert, Floriant; Heuillet, Maud; Rambow, Florian; Bonneil, Eric; Sabourdy, Frédérique; Vincent, Charles; Ait-Arsa, Imade; Levade, Thierry; Thibaut, Pierre; Marine, Jean-Christophe; Portais, Jean-Charles; Sarry, Jean-Emmanuel; Le Cam, Laurent; Linares, Laetitia K

2016-06-16

The mouse double minute 2 (MDM2) oncoprotein is recognized as a major negative regulator of the p53 tumor suppressor, but growing evidence indicates that its oncogenic activities extend beyond p53. Here, we show that MDM2 is recruited to chromatin independently of p53 to regulate a transcriptional program implicated in amino acid metabolism and redox homeostasis. Identification of MDM2 target genes at the whole-genome level highlights an important role for ATF3/4 transcription factors in tethering MDM2 to chromatin. MDM2 recruitment to chromatin is a tightly regulated process that occurs during oxidative stress and serine/glycine deprivation and is modulated by the pyruvate kinase M2 (PKM2) metabolic enzyme. Depletion of endogenous MDM2 in p53-deficient cells impairs serine/glycine metabolism, the NAD(+)/NADH ratio, and glutathione (GSH) recycling, impacting their redox state and tumorigenic potential. Collectively, our data illustrate a previously unsuspected function of chromatin-bound MDM2 in cancer cell metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Materials for Nonaqueous Flow Batteries with a High Coulombic Efficiency and Stable Cycling.

Science.gov (United States)

Milton, Margarita; Cheng, Qian; Yang, Yuan; Nuckolls, Colin; Hernández Sánchez, Raúl; Sisto, Thomas J

2017-12-13

This manuscript presents a working redox battery in organic media that possesses remarkable cycling stability. The redox molecules have a solubility over 1 mol electrons/liter, and a cell with 0.4 M electron concentration is demonstrated with steady performance >450 cycles (>74 days). Such a concentration is among the highest values reported in redox flow batteries with organic electrolytes. The average Coulombic efficiency of this cell during cycling is 99.868%. The stability of the cell approaches the level necessary for a long lifetime nonaqueous redox flow battery. For the membrane, we employ a low cost size exclusion cellulose membrane. With this membrane, we couple the preparation of nanoscale macromolecular electrolytes to successfully avoid active material crossover. We show that this cellulose-based membrane can support high voltages in excess of 3 V and extreme temperatures (-20 to 110 °C). These extremes in temperature and voltage are not possible with aqueous systems. Most importantly, the nanoscale macromolecular platforms we present here for our electrolytes can be readily tuned through derivatization to realize the promise of organic redox flow batteries.

Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

OpenAIRE

Kristina Wedege; Emil Dražević; Denes Konya; Anders Bentien

2016-01-01

Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined ...

New Redox Polymers that Exhibit Reversible Cleavage of Sulfur Bonds as Cathode Materials.

Science.gov (United States)

Baloch, Marya; Ben Youcef, Hicham; Li, Chunmei; Garcia-Calvo, Oihane; Rodriguez, Lide M; Shanmukaraj, Devaraj; Rojo, Teofilo; Armand, Michel

2016-11-23

Two new cathode materials based on redox organosulfur polymers were synthesized and investigated for rechargeable lithium batteries as a proof-of-concept study. These cathodes offered good cycling performance owing to the absence of polysulfide solubility, which plagues Li/S systems. Herein, an aliphatic polyamine or a conjugated polyazomethine was used as the base to tether the redox-active species. The activity comes from the cleavage and formation of S-S or N-S bonds, which is made possible by the rigid conjugated backbone. The synthesized polymers were characterized through FTIR spectroscopy and thermogravimetric analysis (TGA). Galvanostatic measurements were performed to evaluate the discharge/charge cycles and characterize the performance of the lithium-based cells, which displayed initial discharge capacities of approximately 300 mA h g -1 at C/5 over 100 cycles with approximately 98 % Coulombic efficiency. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DHEA attenuates PDGF-induced phenotypic proliferation of vascular smooth muscle A7r5 cells through redox regulation

Energy Technology Data Exchange (ETDEWEB)

Urata, Yoshishige; Goto, Shinji; Kawakatsu, Miho [Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Yodoi, Junji [Department of Biological Responses, Institute for Viral Research, Graduate School of Medicine, Kyoto University, 53 Shogain, Kawahara-cho, Sakyo-ku, Kyoto 606-8397 (Japan); Eto, Masato [Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Akishita, Masahiro, E-mail: akishita-tky@umin.ac.jp [Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Kondo, Takahito [Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

2010-05-28

It is known that dehydroepiandrosterone (DHEA) inhibits a phenotypic switch in vascular smooth muscle cells (VSMC) induced by platelet-derived growth factor (PDGF)-BB. However, the mechanism behind the effect of DHEA on VSMC is not clear. Previously we reported that low molecular weight-protein tyrosine phosphatase (LMW-PTP) dephosphorylates PDGF receptor (PDGFR)-{beta} via a redox-dependent mechanism involving glutathione (GSH)/glutaredoxin (GRX)1. Here we demonstrate that the redox regulation of PDGFR-{beta} is involved in the effect of DHEA on VSMC. DHEA suppressed the PDGF-BB-dependent phosphorylation of PDGFR-{beta}. As expected, DHEA increased the levels of GSH and GRX1, and the GSH/GRX1 system maintained the redox state of LMW-PTP. Down-regulation of the expression of LMW-PTP using siRNA restored the suppression of PDGFR-{beta}-phosphorylation by DHEA. A promoter analysis of GRX1 and {gamma}-glutamylcysteine synthetase ({gamma}-GCS), a rate-limiting enzyme of GSH synthesis, showed that DHEA up-regulated the transcriptional activity at the peroxisome proliferator-activated receptor (PPAR) response element, suggesting PPAR{alpha} plays a role in the induction of GRX1 and {gamma}-GCS expression by DHEA. In conclusion, the redox regulation of PDGFR-{beta} is involved in the suppressive effect of DHEA on VSMC proliferation through the up-regulation of GSH/GRX system.

Ocean redox change at the Permian-Triassic mass extinction

DEFF Research Database (Denmark)

Ruhl, Micha; Bjerrum, Christian J.; Canfield, Donald Eugene

2013-01-01

Earth’s history is marked by multiple events of ocean anoxia developing along continental margins and po¬tentially into the open ocean realm. These events of¬ten coincide with the emplacement of large igneous provinces (LIPs) on continents, major perturbations of global geochemical cycles and mar...... these oceanographic changes to similar observations for the Triassic-Jurassic mass extinction and discuss environmental forcing, poten¬tially inherent to major volcanic events and leading to global environmental change and extinction...... ocean redox change over the largest mass extinction event in Earth history, at the Permian-Tri¬assic boundary (at ~252 Ma). This event is marked by a major perturbation in the global exogenic carbon cycle (and associated major negative carbon isotope excursion (CIE)), likely initiated by carbon...... (anoxic but not euxinic) coinciding with the main extinction event. Molybdenum enrichments, often indicative for freely available sulfide in the water-column, only occur dur¬ing the second phase of euxinia. This pattern of ocean redox-change in Svalbard direct¬ly reflects similar trends in Greenland...

Metabolic Control of Redox and Redox Control of Metabolism in Plants

Science.gov (United States)

Fernie, Alisdair R.

2014-01-01

Abstract Significance: Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. Recent Advances: The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. Critical Issues: It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Future Directions: Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and

The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch.

Science.gov (United States)

Mauney, Christopher H; Rogers, LeAnn C; Harris, Reuben S; Daniel, Larry W; Devarie-Baez, Nelmi O; Wu, Hanzhi; Furdui, Cristina M; Poole, Leslie B; Perrino, Fred W; Hollis, Thomas

2017-12-01

Proliferative signaling involves reversible posttranslational oxidation of proteins. However, relatively few molecular targets of these modifications have been identified. We investigate the role of protein oxidation in regulation of SAMHD1 catalysis. Here we report that SAMHD1 is a major target for redox regulation of nucleotide metabolism and cell cycle control. SAMHD1 is a triphosphate hydrolase, whose function involves regulation of deoxynucleotide triphosphate pools. We demonstrate that the redox state of SAMHD1 regulates its catalytic activity. We have identified three cysteine residues that constitute an intrachain disulfide bond "redox switch" that reversibly inhibits protein tetramerization and catalysis. We show that proliferative signals lead to SAMHD1 oxidation in cells and oxidized SAMHD1 is localized outside of the nucleus. Innovation and Conclusions: SAMHD1 catalytic activity is reversibly regulated by protein oxidation. These data identify a previously unknown mechanism for regulation of nucleotide metabolism by SAMHD1. Antioxid. Redox Signal. 27, 1317-1331.

Flowable Conducting Particle Networks in Redox-Active Electrolytes for Grid Energy Storage

Energy Technology Data Exchange (ETDEWEB)

Hatzell, K. B.; Boota, M.; Kumbur, E. C.; Gogotsi, Y.

2015-01-01

This study reports a new hybrid approach toward achieving high volumetric energy and power densities in an electrochemical flow capacitor for grid energy storage. The electrochemical flow capacitor suffers from high self-discharge and low energy density because charge storage is limited to the available surface area (electric double layer charge storage). Here, we examine two carbon materials as conducting particles in a flow battery electrolyte containing the VO2+/VO2+ redox couple. Highly porous activated carbon spheres (CSs) and multi-walled carbon nanotubes (MWCNTs) are investigated as conducting particle networks that facilitate both faradaic and electric double layer charge storage. Charge storage contributions (electric double layer and faradaic) are distinguished for flow-electrodes composed of MWCNTs and activated CSs. A MWCNT flow-electrode based in a redox-active electrolyte containing the VO2+/VO2+ redox couple demonstrates 18% less self-discharge, 10 X more energy density, and 20 X greater power densities (at 20 mV s-1) than one based on a non-redox active electrolyte. Furthermore, a MWCNT redox-active flow electrode demonstrates 80% capacitance retention, and >95% coulombic efficiency over 100 cycles, indicating the feasibility of utilizing conducting networks with redox chemistries for grid energy storage.

Salicylic acid-induced glutathione status in tomato crop and resistance to root-knot nematode, Meloidogyne incognita (Kofoid & White Chitwood

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Hari C. Meher

2011-10-01

Full Text Available Salicylic acid-(SA is a plant defense stimulator. Exogenous application of SA might influence the status of glutathione-(GSH. GSH activates and SA alters the expression of defense genes to modulate plant resistance against pathogens. The fate of GSH in a crop following SA treatment is largely unknown. The SA-induced profiles of free reduced-, free oxidized-(GSSG and protein bound-(PSSG glutathione in tomato crop following foliar treatment of transplant at 5.0-10.0 μg mL–1 were measured by liquid chromatography. Resistance to root-knot nematode, Meloidogyne incognita damaging tomato and crop performance were also evaluated. SA treatment at 5.0-10.0 μg mL–1 to tomato transplants increased GSH, GSSG and PSSG in plant leaf and root, more so in leaf, during crop growth and development. As the fruits ripened, GSH and PSSG increased and GSSG declined. SA reduced the root infection by M. incognita, nematode reproduction and thus, improved the resistance of tomato var. Pusa Ruby, but reduced crop growth and redox status. SA at 5.0 μg mL–1 improved yield and fruit quality. The study firstly linked SA with activation of glutathione metabolism and provided an additional dimension to the mechanism of induced resistance against obligate nematode pathogen. SA increased glutathione status in tomato crop, imparted resistance against M. incognita, augmented crop yield and functional food quality. SA can be applied at 5.0 μg mL–1 for metabolic engineering of tomato at transplanting to combine host-plant resistance and health benefits in formulating a strategic nematode management decision.

Carbon-free Solid Dispersion LiCoO2 Redox Couple Characterization and Electrochemical Evaluation for All Solid Dispersion Redox Flow Batteries

International Nuclear Information System (INIS)

Qi, Zhaoxiang; Liu, Aaron L.; Koenig, Gary M.

2017-01-01

Highlights: • LiCoO 2 particles can be cycled in carbon-free and binder-free coin cells. • A carbon-free LiCoO 2 suspension is electrochemically oxidized and reduced. • Comparable size LiCoO 2 and Li 4 Ti 5 O 12 suspensions have similar rheological properties. • First demonstration of redox couples with solid suspensions for both electrodes. - Abstract: Semi-solid flow batteries have been reported to have among the highest energy densities for redox flow batteries, however, they rely on percolated carbon networks which increase the electrolyte viscosity significantly. We report the first demonstration of carbon-free redox flow couples comprised of dispersed lithium-ion battery active material suspensions, with sub-micrometer LiCoO 2 (LCO) particles at the cathode and Li 4 Ti 5 O 12 (LTO) particles at the anode. Both electrochemical and rheological properties of the LCO suspensions are reported and compared to previous reports for LTO dispersed electrochemical redox couples. An LTO anode and LCO cathode full cell was constructed and reversible electrochemical redox reaction of the dispersed particles was successfully demonstrated. This carbon-free dispersed lithium-ion active material full cell provides a proof-of-concept for a system that lies between the relatively high viscosity semi-solid flow cells with percolated carbon networks and the relatively low energy density conventional flow cells comprised of dissolved transition metals, providing a system for future study of the trade-off between energy density and viscosity for electrochemical flow cells that rely on solid active materials.

Glutathione role in gallium induced toxicity

African Journals Online (AJOL)

Asim

2012-01-26

GSH) present in tissues. It is very important and interesting to study the reaction of gallium nitrate and glutathione as biomarker of glutathione role in detoxification and conjugation in whole blood components (plasma and ...

Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe.

Science.gov (United States)

Emoto, Miho C; Yamato, Mayumi; Sato-Akaba, Hideo; Yamada, Ken-ichi; Fujii, Hirotada G

2015-11-03

Much evidence supports the idea that oxidative stress is involved in the pathogenesis of epilepsy, and therapeutic interventions with antioxidants are expected as adjunct antiepileptic therapy. The aims of this study were to non-invasively obtain spatially resolved redox data from control and pentylenetetrazole (PTZ)-induced kindled mouse brains by electron paramagnetic resonance (EPR) imaging and to visualize the brain regions that are sensitive to oxidative damage. After infusion of the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), a series of EPR images of PTZ-induced mouse heads were measured. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of redox status in vivo and mapped as a redox map. The obtained redox map showed heterogeneity in the redox status in PTZ-induced mouse brains compared with control. The co-registered image of the redox map and magnetic resonance imaging (MRI) for both control and PTZ-induced mice showed a clear change in the redox status around the hippocampus after PTZ. To examine the role of antioxidants on the brain redox status, the levels of antioxidants were measured in brain tissues of control and PTZ-induced mice. Significantly lower concentrations of glutathione in the hippocampus of PTZ-kindled mice were detected compared with control. From the results of both EPR imaging and the biochemical assay, the hippocampus was found to be susceptible to oxidative damage in the PTZ-induced animal model of epilepsy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of plasma malondialdehyde, glutathione, glutathione peroxidase, hydroxyproline and selenium levels in patients with vitiligo and healthy controls

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Ozturk I

2008-01-01

Full Text Available Background: The etiology and pathophysiologic mechanism of vitiligo are still unclear. The relationship between increased oxidative stress due to the accumulation of radicals and reactive oxygen species and the associated changes in blood and epidermal component of vitiliginous skin have been reported many times. We investigated the possible changes of plasma malondialdehyde, glutathione, selenium, hydroxyproline and glutathione peroxidase activity levels in patients with vitiligo in order to evaluate the relationship between oxidative stress and etiopathogenesis of vitiligo. Materials and Methods: Plasma malondialdehyde, glutathione, hydroxyproline and glutathione peroxidase activity levels were measured by spectrophotometric methods, and HPLC was used for measurement of selenium concentrations. Results: Our results showed increased malondialdehyde, hydroxyproline and glutathione peroxidase activity levels in plasma of vitiligo group ( P < 0.05. Conclusion: Support of antioxidant system via nonenzymatic antioxidant compounds and antioxidant enzymes may be useful to prevent of melanocyte degeneration which occur due to oxidative damage in vitiligo.

A high-energy-density redox flow battery based on zinc/polyhalide chemistry.

Science.gov (United States)

Zhang, Liqun; Lai, Qinzhi; Zhang, Jianlu; Zhang, Huamin

2012-05-01

Zn and the Art of Battery Development: A zinc/polyhalide redox flow battery employs Br(-) /ClBr(2-) and Zn/Zn(2+) redox couples in its positive and negative half-cells, respectively. The performance of the battery is evaluated by charge-discharge cycling tests and reveals a high energy efficiency of 81%, based on a Coulombic efficiency of 96% and voltage efficiency of 84%. The new battery technology can provide high performance and energy density at an acceptable cost. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes cultured in synovial fluid isolated from patients with rheumatoid arthritis

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Michał Gajewski

2016-07-01

Full Text Available Objectives : Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca 2+ ions mobilization or β 2 -integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods : Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils or with or without synovial fluid (85% for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH vs. oxidized glutathione (GSSG ratio and membrane lipid peroxidation evaluation. Results : Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions : Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by

Influence of Iron Speciation on Redox Cycling and Reactivity with Persistent Organic Contaminants

Science.gov (United States)

Kim, Dongwook

2009-01-01

Although a number of past studies have been aimed at characterizing iron's redox properties in aqueous systems and its contribution to natural attenuation processes of groundwater contaminants, many questions remain. It is especially important to understand the molecular properties that control the reactivity of both Fe[superscript II] and…

Lignin decomposition and microbial community in paddy soils: effects of alternating redox conditions

Science.gov (United States)

Cerli, Chiara; Liu, Qin; Hanke, Alexander; Kaiser, Klaus; Kalbitz, Karsten

2013-04-01

Paddy soils are characterised by interchanging cycles of anaerobic and aerobic conditions. Such fluctuations cause continuous changes in soil solution chemistry as well as in the composition and physiological responses of the microbial community. Temporary deficiency in oxygen creates conditions favourable to facultative or obligates anaerobic bacteria, while aerobic communities can thrive in the period of water absence. These alterations can strongly affect soil processes, in particular organic matter (OM) accumulation and mineralization. In submerged soils, lignin generally constitutes a major portion of the total OM because of hampered degradation under anoxic conditions. The alternating redox cycles resulting from paddy soil management might promote both degradation and preservation of lignin, affecting the overall composition and reactivity of total and dissolved OM. We sampled soils subjected to cycles of anoxic (rice growing period) and oxic (harvest and growth of other crops) conditions since 700 and 2000 years. We incubated suspended Ap material, sampled from the two paddy plus two corresponding non-paddy control soils under oxic and anoxic condition, for 3 months, interrupted by a short period of three weeks (from day 21 to day 43) with reversed redox conditions. At each sampling time (day 2, 21, 42, 63, 84), we determined lignin-derived phenols (by CuO oxidation) as well as phospholipids fatty acids contents and composition. We aimed to highlight changes in lignin decomposition as related to the potential rapid changes in microbial community composition. Since the studied paddy soils had a long history of wet rice cultivation, the microbial community should be well adapted to interchanging oxic and anoxic cycles, therefore fully expressing its activity at both conditions. In non-paddy soil changes in redox conditions caused modification of quantity and composition of the microbial community. On the contrary, in well-established paddy soils the microbial

Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells.

Science.gov (United States)

Thangamani, Shankar; Eldesouky, Hassan E; Mohammad, Haroon; Pascuzzi, Pete E; Avramova, Larisa; Hazbun, Tony R; Seleem, Mohamed N

2017-01-01

Ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear. The antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, Cryptococcus neoformans, and C. gattii clinical isolates. Chemogenomic profiling and biochemical assays were employed to identify the antifungal target of ebselen. Ebselen's antifungal activity in vivo was investigated in a Caenorhabditis elegans animal model. Ebselen exhibits potent antifungal activity against both Candida spp. and Cryptococcus spp., at concentrations ranging from 0.5 to 2μg/ml. Ebselen rapidly eradicates a high fungal inoculum within 2h of treatment. Investigation of the drug's antifungal mechanism of action indicates that ebselen depletes intracellular glutathione (GSH) levels, leading to increased production of reactive oxygen species (ROS), and thereby disturbs the redox homeostasis in fungal cells. Examination of ebselen's in vivo antifungal activity in two Caenorhabditis elegans models of infection demonstrate that ebselen is superior to conventional antifungal drugs (fluconazole, flucytosine and amphotericin) in reducing Candida and Cryptococcus fungal load. Ebselen possesses potent antifungal activity against clinically relevant isolates of both Candida and Cryptococcus by regulating GSH and ROS production. The potent in vivo antifungal activity of ebselen supports further investigation for repurposing it for use as an antifungal agent. The present study shows that ebselen targets glutathione and also support that glutathione as a potential target for antifungal drug development. Copyright © 2016 Elsevier B.V. All rights reserved.

Short-term exercise worsens cardiac oxidative stress and fibrosis in 8-month-old db/db mice by depleting cardiac glutathione.

Science.gov (United States)

Laher, Ismail; Beam, Julianne; Botta, Amy; Barendregt, Rebekah; Sulistyoningrum, Dian; Devlin, Angela; Rheault, Mark; Ghosh, Sanjoy

2013-01-01

Moderate exercise improves cardiac antioxidant status in young humans and animals with Type-2 diabetes (T2D). Given that both diabetes and advancing age synergistically decrease antioxidant expression in most tissues, it is unclear whether exercise can upregulate cardiac antioxidants in chronic animal models of T2D. To this end, 8-month-old T2D and normoglycemic mice were exercised for 3 weeks, and cardiac redox status was evaluated. As expected, moderate exercise increased cardiac antioxidants and attenuated oxidative damage in normoglycemic mice. In contrast, similar exercise protocol in 8-month-old db/db mice worsened cardiac oxidative damage, which was associated with a specific dysregulation of glutathione (GSH) homeostasis. Expression of enzymes for GSH biosynthesis [γ-glutamylcysteine synthase, glutathione reductase] as well as for GSH-mediated detoxification (glutathione peroxidase, glutathione-S-transferase) was lower, while toxic metabolites dependent on GSH for clearance (4-hydroxynonenal) were increased in exercised diabetic mice hearts. To validate GSH loss as an important factor for such aggravated damage, daily administration of GSH restored cardiac GSH levels in exercised diabetic mice. Such supplementation attenuated both oxidative damage and fibrotic changes in the myocardium. Expression of transforming growth factor beta (TGF-β) and its regulated genes which are responsible for such profibrotic changes were also attenuated with GSH supplementation. These novel findings in a long-term T2D animal model demonstrate that short-term exercise by itself can deplete cardiac GSH and aggravate cardiac oxidative stress. As GSH administration conferred protection in 8-month-old diabetic mice undergoing exercise, supplementation with GSH-enhancing agents may be beneficial in elderly diabetic patients undergoing exercise.

Redox Modulation Matters: Emerging Functions for Glutaredoxins in Plant Development and Stress Responses

Directory of Open Access Journals (Sweden)

Shutian Li

2014-11-01

Full Text Available Glutaredoxins (GRXs are small ubiquitous glutathione (GSH-dependent oxidoreductases that catalyze the reversible reduction of protein disulfide bridges or protein-GSH mixed disulfide bonds via a dithiol or monothiol mechanism, respectively. Three major classes of GRXs, with the CPYC-type, the CGFS-type or the CC-type active site, have been identified in many plant species. In spite of the well-characterized roles for GRXs in Escherichia coli, yeast and humans, the biological functions of plant GRXs have been largely enigmatic. The CPYC-type and CGFS-type GRXs exist in all organisms, from prokaryotes to eukaryotes, whereas the CC-type class has thus far been solely identified in land plants. Only the number of the CC-type GRXs has enlarged dramatically during the evolution of land plants, suggesting their participation in the formation of more complex plants adapted to life on land. A growing body of evidence indicates that plant GRXs are involved in numerous cellular pathways. In this review, emphasis is placed on the recently emerging functions for GRXs in floral organ development and disease resistance. Notably, CC-type GRXs have been recruited to participate in these two seemingly unrelated processes. Besides, the current knowledge of plant GRXs in the assembly and delivery of iron-sulfur clusters, oxidative stress responses and arsenic resistance is also presented. As GRXs require GSH as an electron donor to reduce their target proteins, GSH-related developmental processes, including the control of flowering time and the development of postembryonic roots and shoots, are further discussed. Profiling the thiol redox proteome using high-throughput proteomic approaches and measuring cellular redox changes with fluorescent redox biosensors will help to further unravel the redox-regulated physiological processes in plants.

A novel and high-effective redox-mediated gel polymer electrolyte for supercapacitor

International Nuclear Information System (INIS)

Ma, Guofu; Feng, Enke; Sun, Kanjun; Peng, Hui; Li, Jiajia; Lei, Ziqiang

2014-01-01

Graphical abstract: - Highlights: • Alkali and P-phenylenediamine doped polyvinyl alcohol gel electrolyte is prepared. • The PVA-KOH-PPD gel electrolyte can also be used as separator. • The introduction of PPD increases the ionic conductivity of electrolyte. • The supercapacitor exhibits flexible and high energy density. - Abstract: A supercapacitor utilize a novel redox-mediated gel polymer (PVA-KOH-PPD) as electrolyte and separator, and activated carbon as electrodes is assembled. The PVA-KOH-PPD gel polymer as potential electrolyte for supercapacitor is investigated by cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy techniques. It is found that the supercapacitor exhibits high ionic conductivity (25 mS cm −1 ), large electrode specific capacitance (611 F g −1 ) and high energy density (82.56 Wh kg −1 ). The high performance is attributed to the addition of quick redox reactions at the electrolyte|electrode interface as PPD undergoes a two-proton/two-electron reduction and oxidation during cycling. Furthermore, the supercapacitor with PVA-KOH-PPD gel polymer shows excellent charge-discharge stability, after 1000 charge-discharge cycles, the supercapacitor still retains a high electrode specific capacitance of 470 F g −1 . It is believed that the idea using redox mediator has a good prospect for improving the performances of supercapacitors

Chloroplast Redox Poise

DEFF Research Database (Denmark)

Steccanella, Verdiana

the redox status of the plastoquinone pool and chlorophyll biosynthesis. Furthermore, in the plant cell, the equilibrium between redox reactions and ROS signals is also maintained by various balancing mechanisms among which the thioredoxin reductase-thioredoxin system (TR-Trx) stands out as a mediator......The redox state of the chloroplast is maintained by a delicate balance between energy production and consumption and is affected by the need to avoid increased production of reactive oxygen species (ROS). Redox power and ROS generated in the chloroplast are essential for maintaining physiological...... metabolic pathways and for optimizing chloroplast functions. The redox poise of photosynthetic electron transport components like plastoquinone is crucial to initiate signaling cascades and might also be involved in key biosynthetic pathways such as chlorophyll biosynthesis. We, therefore, explored...

Hourly and daily variation of sediment redox potential in tidal wetland sediments

Science.gov (United States)

Catallo, W. James

1999-01-01

Variation of electrochemical oxidation-reduction (redox) potential was examined in surface salt march sediments under conditions of flooding and tidal simulation in mesocosms and field sites. Time series were generated of redox potential measured in sediment profiles at 2-10 cm depth using combination Pt-Ag/AgCl (ORP) electrodes. Redox potential data were acquired at rapid rates (1-55 samples/h) over extended periods (3-104 days) along with similar times series of temperature (water, air, soil) and pH. It was found that redox potential vaired as a result of water level changes and was unrelated to diurnal changes in temperature or pH, the latter of which changed by 370 mV redox potential decrease in under 48 hours). Attenuatoin of microbial activity by [gamma] y-radiation and toxic chemicals elimintated this response. In tidal salt marsh mesocosms where the sediment-plant assemblages were exposed to a simulated diurnal tide, redox potenial oscillations of 40-300 mV amplitude were recoded that has the same periodicity as the flood-drain cycle. Periodic redoc potential time series were observed repeatedly in sediments receiving tidal pulsing but not in those sediments exposed to static hydrological conditions. Data collected over 12 days from a coastal marsh site experiencing diurnal tides showed similar fluctuations in redox potential. Data from the experimentents indicated that (a) redox potential can be a dynamic, nonlinear variable in coastal and estuarine wetland sediments over hourly and daily scales, and the designs of biogeochemical experiments should reflect this, (b) redox potential can change rapidly and signigicantly in coastal wetland sediments in response of flooding and draining, (c) microbial community processes are primarily determinants of the time course of redox potential in wetland sediments, and elimination of inhibition of microbial activity (e.g. by pollutants) can significantly alter that behavior, and (d) fast redox potential dynamics appear

Phytoextraction of toxic metals: a central role for glutathione.

Science.gov (United States)

Seth, C S; Remans, T; Keunen, E; Jozefczak, M; Gielen, H; Opdenakker, K; Weyens, N; Vangronsveld, J; Cuypers, A

2012-02-01

Phytoextraction has a promising potential as an environmentally friendly clean-up method for soils contaminated with toxic metals. To improve the development of efficient phytoextraction strategies, better knowledge regarding metal uptake, translocation and detoxification in planta is a prerequisite. This review highlights our current understanding on these mechanisms, and their impact on plant growth and health. Special attention is paid to the central role of glutathione (GSH) in this process. Because of the high affinity of metals to thiols and as a precursor for phytochelatins (PCs), GSH is an essential metal chelator. Being an important antioxidant, a direct link between metal detoxification and the oxidative challenge in plants growing on contaminated soils is observed, where GSH could be a key player. In addition, as redox couple, oxidized and reduced GSH transmits specific information, in this way tuning cellular signalling pathways under environmental stress conditions. Possible improvements of phytoextraction could be achieved by using transgenic plants or plant-associated microorganisms. Joined efforts should be made to cope with the challenges faced with phytoextraction in order to successfully implement this technique in the field. © 2011 Blackwell Publishing Ltd.

Measurement of glutathione-protein mixed disulfides

International Nuclear Information System (INIS)

Livesey, J.C.; Reed, D.J.

1984-01-01

The development of a sensitive and highly specific assay for the presence of mixed disulfides between protein thiol groups and endogenous thiols has been undertaken. Previous investigations on the concentrations of glutathione (GSH), glutathione disulfide (GSSG) and protein glutathione mixed disulfides (ProSSG) have been of limited usefulness because of the poor specificity of the assays used. Our assay for these forms of glutathione is based on high performance liquid chromatography (HPLC) and is an extension of an earlier method. After perchloric acid precipitation, the protein sample is washed with an organic solvent to fully denature the protein. Up to a 10-fold increase in GSH released from fetal bovine serum (FBS) protein has been found when the protein precipitate is washed with ethanol rather than ether, as earlier suggested. Similar effects have been observed with an as yet unidentified thiol which elutes in the chromatography system with a retention volume similar to cysteine

High-energy density nonaqueous all redox flow lithium battery enabled with a polymeric membrane.

Science.gov (United States)

Jia, Chuankun; Pan, Feng; Zhu, Yun Guang; Huang, Qizhao; Lu, Li; Wang, Qing

2015-11-01

Redox flow batteries (RFBs) are considered one of the most promising large-scale energy storage technologies. However, conventional RFBs suffer from low energy density due to the low solubility of the active materials in electrolyte. On the basis of the redox targeting reactions of battery materials, the redox flow lithium battery (RFLB) demonstrated in this report presents a disruptive approach to drastically enhancing the energy density of flow batteries. With LiFePO4 and TiO2 as the cathodic and anodic Li storage materials, respectively, the tank energy density of RFLB could reach ~500 watt-hours per liter (50% porosity), which is 10 times higher than that of a vanadium redox flow battery. The cell exhibits good electrochemical performance under a prolonged cycling test. Our prototype RFLB full cell paves the way toward the development of a new generation of flow batteries for large-scale energy storage.

High–energy density nonaqueous all redox flow lithium battery enabled with a polymeric membrane

Science.gov (United States)

Jia, Chuankun; Pan, Feng; Zhu, Yun Guang; Huang, Qizhao; Lu, Li; Wang, Qing

2015-01-01

Redox flow batteries (RFBs) are considered one of the most promising large-scale energy storage technologies. However, conventional RFBs suffer from low energy density due to the low solubility of the active materials in electrolyte. On the basis of the redox targeting reactions of battery materials, the redox flow lithium battery (RFLB) demonstrated in this report presents a disruptive approach to drastically enhancing the energy density of flow batteries. With LiFePO4 and TiO2 as the cathodic and anodic Li storage materials, respectively, the tank energy density of RFLB could reach ~500 watt-hours per liter (50% porosity), which is 10 times higher than that of a vanadium redox flow battery. The cell exhibits good electrochemical performance under a prolonged cycling test. Our prototype RFLB full cell paves the way toward the development of a new generation of flow batteries for large-scale energy storage. PMID:26702440

Investigation of Iron Oxide Morphology in a Cyclic Redox Water Splitting Process for Hydrogen Generation

Directory of Open Access Journals (Sweden)

Michael M. Bobek

2012-10-01

Full Text Available A solar fuels generation research program is focused on hydrogen production by means of reactive metal water splitting in a cyclic iron-based redox process. Iron-based oxides are explored as an intermediary reactive material to dissociate water molecules at significantly reduced thermal energies. With a goal of studying the resulting oxide chemistry and morphology, chemical assistance via CO is used to complete the redox cycle. In order to exploit the unique characteristics of highly reactive materials at the solar reactor scale, a monolithic laboratory scale reactor has been designed to explore the redox cycle at temperatures ranging from 675 to 875 K. Using high resolution scanning electron microscope (SEM and electron dispersive X-ray spectroscopy (EDS, the oxide morphology and the oxide state are quantified, including spatial distributions. These images show the change of the oxide layers directly after oxidation and after reduction. The findings show a significant non-stoichiometric O/Fe gradient in the atomic ratio following oxidation, which is consistent with a previous kinetics model, and a relatively constant, non-stoichiometric O/Fe atomic ratio following reduction.

The geochemical record of the ancient nitrogen cycle, nitrogen isotopes, and metal cofactors.

Science.gov (United States)

Godfrey, Linda V; Glass, Jennifer B

2011-01-01

The nitrogen (N) cycle is the only global biogeochemical cycle that is driven by biological functions involving the interaction of many microorganisms. The N cycle has evolved over geological time and its interaction with the oxygen cycle has had profound effects on the evolution and timing of Earth's atmosphere oxygenation (Falkowski and Godfrey, 2008). Almost every enzyme that microorganisms use to manipulate N contains redox-sensitive metals. Bioavailability of these metals has changed through time as a function of varying redox conditions, and likely influenced the biological underpinnings of the N cycle. It is possible to construct a record through geological time using N isotopes and metal concentrations in sediments to determine when the different stages of the N cycle evolved and the role metal availability played in the development of key enzymes. The same techniques are applicable to understanding the operation and changes in the N cycle through geological time. However, N and many of the redox-sensitive metals in some of their oxidation states are mobile and the isotopic composition or distribution can be altered by subsequent processes leading to erroneous conclusions. This chapter reviews the enzymology and metal cofactors of the N cycle and describes proper utilization of methods used to reconstruct evolution of the N cycle through time. Copyright © 2011 Elsevier Inc. All rights reserved.

Active biomonitoring of a subtropical river using glutathione-S ...

African Journals Online (AJOL)

Active biomonitoring of a subtropical river using glutathione-S-transferase (GST) and heat shock proteins (HSP 70) in. Oreochromis niloticusas surrogate biomarkers of metal contamination. Victor Kurauone Muposhi1, Beaven Utete1*, Idah Sithole-Niang2 and Stanley Mukangenyama2. 1Wildlife Ecology and Conservation, ...

Redox Behavior of Fe2+/Fe3+ Redox Couple by Absorption Spectroscopy and Measurement

International Nuclear Information System (INIS)

Oh, J. Y.; Park, S.; Yun, J. I.

2010-01-01

Redox behavior has influences on speciation and other geochemical reactions of radionuclides such as sorption, solubility, and colloid formation, etc. It is one of the factors for evaluation of long-term safety assessment under high-level radioactive waste (HLW) disposal conditions. Accordingly, redox potential (Eh) measurement in aquatic system is important to investigate the redox conditions. Eh is usually measured with redox active electrodes (Pt, Au, glassy carbon, etc.). Nevertheless, Eh measurements by general methods using electrodes provide low accuracy and high uncertainty problem. Therefore, Eh calculated from the concentration of redox active elements with a proper complexing reagent by using UV-Vis absorption spectroscopy is progressed. Iron exists mostly as spent nuclear waste container material and in hydro-geologic minerals. In this system, iron controls the redox condition in near-field area and influences chemical behavior and speciation of radionuclides including redox sensitive actinides such as U, Np, and Pu. In the present work, we present the investigation on redox phenomena of iron in aquatic system by a combination of absorption spectroscopy and redox potential measurements

Intracellular glutathione status regulates mouse bone marrow monocyte-derived macrophage differentiation and phagocytic activity

International Nuclear Information System (INIS)

Kim, Jin-Man; Kim, Hyunsoo; Kwon, Soon Bok; Lee, Soo Young; Chung, Sung-Chang; Jeong, Dae-Won; Min, Byung-Moo

2004-01-01

Although a redox shift can regulate the development of cells, including proliferation, differentiation, and survival, the role of the glutathione (GSH) redox status in macrophage differentiation remains unclear. In order to elucidate the role of a redox shift, macrophage-like cells were differentiated from the bone marrow-derived monocytes that were treated with a macrophage colony stimulating factor (M-CSF or CSF-1) for 3 days. The macrophagic cells were characterized by a time-dependent increase in three major symptoms: the number of phagocytic cells, the number of adherent cells, and the mRNA expression of c-fms, a M-CSF receptor that is one of the macrophage-specific markers and mediates development signals. Upon M-CSF-driven macrophage differentiation, the GSH/GSSG ratio was significantly lower on day 1 than that observed on day 0 but was constant on days 1-3. To assess the effect of the GSH-depleted and -repleted status on the differentiation and phagocytosis of the macrophages, GSH depletion by BSO, a specific inhibitor of the de novo GSH synthesis, inhibited the formation of the adherent macrophagic cells by the down-regulation of c-fms, but did not affect the phagocytic activity of the macrophages. To the contrary, GSH repletion by the addition of NAC, which is a GSH precursor, or reduced GSH in media had no effect on macrophage differentiation, and led to a decrease in the phagocytic activity. Furthermore, we observed that there is checkpoint that is capable of releasing from the inhibition of the formation of the adherent macrophagic cells according to GSH depletion by BSO. Summarizing, these results indicate that the intracellular GSH status plays an important role in the differentiation and phagocytosis of macrophages

pH/redox dual-sensitive dextran nanogels for enhanced intracellular drug delivery.

Science.gov (United States)

Curcio, Manuela; Diaz-Gomez, Luis; Cirillo, Giuseppe; Concheiro, Angel; Iemma, Francesca; Alvarez-Lorenzo, Carmen

2017-08-01

pH/redox dual-responsive nanogels (DEX-SS) were prepared by precipitation polymerization of methacrylated dextran (DEXMA), 2-aminoethylmethacrylate (AEMA) and N,N'-bis(acryloyl)cystamine (BAC), and then loaded with methotrexate (MTX). Nanogels were spherical and exhibited homogeneous size distribution (460nm, PDI<0.30) as observed using dynamic light scattering (DLS) and scanning electron microscopy (SEM). DEX-SS were sensitive to the variations of pH and redox environment. Nanogels incubated in buffer pH 5.0 containing 10mM glutathione (GSH) synergistically increased the mean diameter and the PDI to 750nm and 0.42, respectively. In vitro release experiments were performed at pH 7.4 and 5.0 with and without GSH. The cumulative release of MTX in pH 5.0 medium with 10mMGSH was 5-fold higher than that recorded at pH 7.4 without GSH. Fibroblasts and tumor cells were used to tests the effects of blank DEX-SS and MTX@DEX-SS nanogels on cell viability. Remarkable influence of pH on nanogels internalization into HeLa cells was evidenced by means of confocal microscopy and flow cytometry. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased oxidative stress and antioxidant expression in mouse keratinocytes following exposure to paraquat

International Nuclear Information System (INIS)

Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.; Laskin, Debra L.; Heck, Diane E.; Laskin, Jeffrey D.

2008-01-01

Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which was greater in differentiated cells. Paraquat treatment also resulted in increased expression of HO-1, Cu,Zn-SOD, catalase, GSTP1, GSTA3 and GSTA4. However, no major differences in expression of these enzymes were evident between undifferentiated and differentiated cells. In contrast, expression of GSTA1-2 was significantly greater in differentiated relative to undifferentiated cells after paraquat treatment. No changes in expression of MT-2, Mn-SOD, GPx-1, GSTM1 or the microsomal GST's mGST1, mGST2 and mGST3, were observed in response to paraquat. These data demonstrate that paraquat induces oxidative stress in keratinocytes leading to increased expression of antioxidant genes. These intracellular proteins may be important in protecting the skin from paraquat-mediated cytotoxicity

Synthesis, DNA Cleavage Activity, Cytotoxicity, Acetylcholinesterase Inhibition, and Acute Murine Toxicity of Redox-Active Ruthenium(II) Polypyridyl Complexes.

Science.gov (United States)

Alatrash, Nagham; Narh, Eugenia S; Yadav, Abhishek; Kim, Mahn-Jong; Janaratne, Thamara; Gabriel, James; MacDonnell, Frederick M

2017-07-06

Four mononuclear [(L-L) 2 Ru(tatpp)] 2+ and two dinuclear [(L-L) 2 Ru(tatpp)Ru(L-L) 2 ] 4+ ruthenium(II) polypyridyl complexes (RPCs) containing the 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) ligand were synthesized, in which L-L is a chelating diamine ligand such as 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me 4 phen) or 4,7-diphenyl-1,10-phenanthroline (Ph 2 phen). These Ru-tatpp analogues all undergo reduction reactions with modest reducing agents, such as glutathione (GSH), at pH 7. These, plus several structurally related but non-redox-active RPCs, were screened for DNA cleavage activity, cytotoxicity, acetylcholinesterase (AChE) inhibition, and acute mouse toxicity, and their activities were examined with respect to redox activity and lipophilicity. All of the redox-active RPCs show single-strand DNA cleavage in the presence of GSH, whereas none of the non-redox-active RPCs do. Low-micromolar cytotoxicity (IC 50 ) against malignant H358, CCL228, and MCF7 cultured cell lines was mainly restricted to the redox-active RPCs; however, they were substantially less toxic toward nonmalignant MCF10 cells. The IC 50 values for AChE inhibition in cell-free assays and the acute toxicity of RPCs in mice revealed that whereas most RPCs show potent inhibitory action against AChE (IC 50 values <15 μm), Ru-tatpp complexes as a class are surprisingly well tolerated in animals relative to other RPCs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper increases the ability of 6-hydroxydopamine to generate oxidative stress and the ability of ascorbate and glutathione to potentiate this effect: potential implications in Parkinson's disease.

Science.gov (United States)

Cruces-Sande, Antón; Méndez-Álvarez, Estefanía; Soto-Otero, Ramón

2017-06-01

Copper is an essential metal for the function of many proteins related to important cellular reactions and also involved in the synaptic transmission. Although there are several mechanisms involved in copper homeostasis, a dysregulation in this process can result in serious neurological consequences, including degeneration of dopaminergic neurons. 6-Hydroxydopamine is a dopaminergic neurotoxin mainly used in experimental models of Parkinson's disease, whose neurotoxicity has been related to its ability to generate free radicals. In this study, we examined the effects induced by copper on 6-OHDA autoxidation. Our data show that both Cu + and Cu 2+ caused an increase in • OH production by 6-OHDA autoxidation, which was accompanied by an increase in the rate of both p-quinone formation and H 2 O 2 accumulation. The presence of ascorbate greatly enhanced this process by establishing a redox cycle which regenerates 6-OHDA from its p-quinone. However, the presence of glutathione did not change significantly the copper-induced effects. We observed that copper is able to potentiate the ability of 6-OHDA to cause both lipid peroxidation and protein oxidation, with the latter including a reduction in free-thiol content and an increase in carbonyl content. Ascorbate also increases the lipid peroxidation induced by the action of copper and 6-OHDA. Glutathione protects against the copper-induced lipid peroxidation, but does not reduce its potential to oxidize free thiols. These results clearly demonstrate the potential of copper to increase the capacity of 6-OHDA to generate oxidative stress and the ability of ascorbate to enhance this potential, which may contribute to the destruction of dopaminergic neurons. © 2017 International Society for Neurochemistry.

Chemical resilience of clay rich barrier materials to redox-oscillating conditions and implications for contaminant mobility

International Nuclear Information System (INIS)

Parsons, Chris; Rossetto, Lionel; Charlet, Laurent; Made, Benoit

2012-01-01

nitrate and sulphate in addition to the reductive dissolution of manganese and iron oxide minerals and an increase in CO 2 partial pressure. Whilst some authors demonstrate that such cyclic redox conditions may alter the properties of clay barrier materials due to illitisation of smectite clays (6, 7), the dynamic chemical conditions occurring during redox cycling may also result in the dissolution and re-precipitation of metal oxides, sulphides and carbonates. The balance of these minerals, even if present at sub-per cent levels as impurities has the potential to dramatically alter contaminant mobility. Many inorganic contaminants often associated with LL-LLW including Sb, Cr, As, Hg and U are also highly sensitive to changes in redox conditions which may result in changes to their speciation, toxicity and mobility (8, 9). We demonstrate through the combination of redox-stat batch-reactor experiments and thermodynamic modelling that periodic and cumulative changes to matrix mineralogy, contaminant speciation and mineral surface properties occur following periodic cycles of reduction and oxidation. These changes result in both short term (intra-cycle) and long-term (inter-cycle) changes to K d values for a range of redox sensitive contaminants associated with LL-LLW including arsenic, chromium, selenium, mercury and uranium (Table 1 and Figures 1 and 2). During a series of laboratory experiments argillaceous substrates were subjected to successive cycles of oxidising and reducing conditions with Eh oscillating between -215 and +340 mV induced via both abiotic and microbial methods. Chemically induced cycles of oxidation and reduction were achieved via a combination of gas sparging (nitrogen vs compressed air) and the addition of a synthetic reduced humic substance analogue (AH 2 DS 2- ). Microbially induced cycles of oxidation and reduction were achieved using gas sparging (nitrogen vs compressed air) to stimulate different metabolic pathways of a natively present

Hydrologic control on redox and nitrogen dynamics in a peatland soil

International Nuclear Information System (INIS)

Rubol, Simonetta; Silver, Whendee L.; Bellin, Alberto

2012-01-01

Soils are a dominant source of nitrous oxide (N 2 O), a potent greenhouse gas. However, the complexity of the drivers of N 2 O production and emissions has hindered our ability to predict the magnitude and spatial dynamics of N 2 O fluxes. Soil moisture can be considered a key driver because it influences oxygen (O 2 ) supply, which feeds back on N 2 O sources (nitrification versus denitrification) and sinks (reduction to dinitrogen). Soil water content is directly linked to O 2 and redox potential, which regulate microbial metabolism and chemical transformations in the environment. Despite its importance, only a few laboratory studies have addressed the effects of hydrological transient dynamics on nitrogen (N) cycling in the vadose zone. To further investigate these aspects, we performed a long term experiment in a 1.5 m depth soil column supplemented by chamber experiments. With this experiment, we aimed to investigate how soil moisture dynamics influence redox sensitive N cycling in a peatland soil. As expected, increased soil moisture lowered O 2 concentrations and redox potential in the soil. The decline was more severe for prolonged saturated conditions than for short events and at deep than at the soil surface. Gaseous and dissolved N 2 O, dissolved nitrate (NO 3 − ) and ammonium (NH 4 + ) changed considerably along the soil column profile following trends in soil O 2 and redox potential. Hot spots of N 2 O concentrations corresponded to high variability in soil O 2 in the upper and lower parts of the column. Results from chamber experiments confirmed high NO 3 − reduction potential in soils, particularly from the bottom of the column. Under our experimental conditions, we identified a close coupling of soil O 2 and N 2 O dynamics, both of which lagged behind soil moisture changes. These results highlight the relationship among soil hydrologic properties, redox potential and N cycling, and suggest that models working at a daily scale need to consider

Membrane accessibility of glutathione

DEFF Research Database (Denmark)

Garcia, Almudena; Eljack, N., D.; Sani, ND

2015-01-01

Regulation of the ion pumping activity of the Na(+),K(+)-ATPase is crucial to the survival of animal cells. Recent evidence has suggested that the activity of the enzyme could be controlled by glutathionylation of cysteine residue 45 of the β-subunit. Crystal structures so far available indicate...... that this cysteine is in a transmembrane domain of the protein. Here we have analysed via fluorescence and NMR spectroscopy as well as molecular dynamics simulations whether glutathione is able to penetrate into the interior of a lipid membrane. No evidence for any penetration of glutathione into the membrane...

Thiol-Disulfide Exchange between Glutaredoxin and Glutathione

DEFF Research Database (Denmark)

Iversen, Rasmus; Andersen, Peter Anders; Jensen, Kristine Steen

2010-01-01

Glutaredoxins are ubiquitous thiol-disulfide oxidoreductases which catalyze the reduction of glutathione-protein mixed disulfides. Belonging to the thioredoxin family, they contain a conserved active site CXXC motif. The N-proximal active site cysteine can form a mixed disulfide with glutathione ...... has been replaced with serine. The exchange reaction between the reduced protein and oxidized glutathione leading to formation of the mixed disulfide could readily be monitored by isothermal titration calorimetry (ITC) due to the enthalpic contributions from the noncovalent interactions...

Redox sensor proteins for highly sensitive direct imaging of intracellular redox state.

Science.gov (United States)

Sugiura, Kazunori; Nagai, Takeharu; Nakano, Masahiro; Ichinose, Hiroshi; Nakabayashi, Takakazu; Ohta, Nobuhiro; Hisabori, Toru

2015-02-13

Intracellular redox state is a critical factor for fundamental cellular functions, including regulation of the activities of various metabolic enzymes as well as ROS production and elimination. Genetically-encoded fluorescent redox sensors, such as roGFP (Hanson, G. T., et al. (2004)) and Redoxfluor (Yano, T., et al. (2010)), have been developed to investigate the redox state of living cells. However, these sensors are not useful in cells that contain, for example, other colored pigments. We therefore intended to obtain simpler redox sensor proteins, and have developed oxidation-sensitive fluorescent proteins called Oba-Q (oxidation balance sensed quenching) proteins. Our sensor proteins derived from CFP and Sirius can be used to monitor the intracellular redox state as their fluorescence is drastically quenched upon oxidation. These blue-shifted spectra of the Oba-Q proteins enable us to monitor various redox states in conjunction with other sensor proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Atypical Thioredoxins in Poplar: The Glutathione-Dependent Thioredoxin-Like 2.1 Supports the Activity of Target Enzymes Possessing a Single Redox Active Cysteine1[W

Science.gov (United States)

Chibani, Kamel; Tarrago, Lionel; Gualberto, José Manuel; Wingsle, Gunnar; Rey, Pascal; Jacquot, Jean-Pierre; Rouhier, Nicolas

2012-01-01

Plant thioredoxins (Trxs) constitute a complex family of thiol oxidoreductases generally sharing a WCGPC active site sequence. Some recently identified plant Trxs (Clot, Trx-like1 and -2, Trx-lilium1, -2, and -3) display atypical active site sequences with altered residues between the two conserved cysteines. The transcript expression patterns, subcellular localizations, and biochemical properties of some representative poplar (Populus spp.) isoforms were investigated. Measurements of transcript levels for the 10 members in poplar organs indicate that most genes are constitutively expressed. Using transient expression of green fluorescent protein fusions, Clot and Trx-like1 were found to be mainly cytosolic, whereas Trx-like2.1 was located in plastids. All soluble recombinant proteins, except Clot, exhibited insulin reductase activity, although with variable efficiencies. Whereas Trx-like2.1 and Trx-lilium2.2 were efficiently regenerated both by NADPH-Trx reductase and glutathione, none of the proteins were reduced by the ferredoxin-Trx reductase. Only Trx-like2.1 supports the activity of plastidial thiol peroxidases and methionine sulfoxide reductases employing a single cysteine residue for catalysis and using a glutathione recycling system. The second active site cysteine of Trx-like2.1 is dispensable for this reaction, indicating that the protein possesses a glutaredoxin-like activity. Interestingly, the Trx-like2.1 active site replacement, from WCRKC to WCGPC, suppresses its capacity to use glutathione as a reductant but is sufficient to allow the regeneration of target proteins employing two cysteines for catalysis, indicating that the nature of the residues composing the active site sequence is crucial for substrate selectivity/recognition. This study provides another example of the cross talk existing between the glutathione/glutaredoxin and Trx-dependent pathways. PMID:22523226

Redox Regulation of Mitochondrial Function

Science.gov (United States)

Handy, Diane E.

2012-01-01

Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

Electrolyte for stable cycling of high-energy lithium sulfur redox flow batteries

Science.gov (United States)

Xiao, Jie; Liu, Jun; Pan, Huilin; Henderson, Wesley A.

2018-04-24

A device comprising: a lithium sulfur redox flow battery comprising an electrolyte composition comprising: (i) a dissolved Li2Sx electroactive salt, wherein x.gtoreq.4; (ii) a solvent selected from dimethyl sulfoxide, tetrahydrofuran, or a mixture thereof; and (iii) a supporting salt at a concentration of at least 2 M, as measured by moles of supporting salt divided by the volume of the solvent without considering the volume change of the electrolyte after dissolving the supporting salt.

Integrated Haematological Profiles of Redox Status, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Carla Lubrano

2015-01-01

Full Text Available The pathogenesis of obesity (OB and metabolic syndrome (MetS implies free radical-, oxidized lipid- (LOOH-, and inflammatory cytokine-mediated altered pathways in target organs. Key elements of the transition from benign OB to unhealthy OB+MetS remain unclear. Here, we measured a panel of redox, antioxidant, and inflammation markers in the groups of OB patients (67 with, 45 without MetS and 90 controls. Both OB groups displayed elevated levels of adipokines and heavy oxidative stress (OS evidenced by reduced levels of glutathione, downregulated glutathione-S-transferase, increased 4-hydroxynonenal-protein adducts, reactive oxygen species, and membrane-bound monounsaturated fatty acids (MUFA. Exclusively in OB+MetS, higher-than-normal glutathione peroxidase activity, tumor necrosis factor-α, and other proinflammatory cytokines/chemokines/growth factors were observed; a combination of high adipokine plasminogen activator inhibitor-1 and MUFA was consistent with increased cardiovascular risk. The uncomplicated OB group showed features of adaptation to OS such as decreased levels of vitamin E, activated superoxide dismutase, and inhibited catalase, suggesting H2O2 hyperproduction. Proinflammatory cytokine pattern was normal, except few markers like RANTES, a suitable candidate for therapeutic approaches to prevent a setting of MetS by inhibition of LOOH-primed leukocyte chemotaxis/recruitment to target tissues.

Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in Caco-2 cells

NARCIS (Netherlands)

Usta, M.; Wortelboer, H.M.; Vervoort, J.J.M.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, van P.J.; Cnubben, N.H.P.

2007-01-01

Curcumin, an alpha,beta-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional H-1 NMR

Electrochemical determination of glutathione in plasma at carbon nanotubes based screen printed electrodes.

Science.gov (United States)

Turunc, Ezgi; Karadeniz, Hakan; Armagan, Guliz; Erdem, Arzum; Yalcin, Ayfer

2013-11-01

Glutathione (GSH) is a major endogenous antioxidant highly active in human tissues and plays a key role in controlling cellular thiol redox system, maintaining the immune and detoxification system. The determination of GSH levels in tissue is important to estimate endogenous defenses against oxidative stress. In our study, the multi-walled carbon nanotube modified screen-printed electrodes (MWCNT-SPEs) were used to determine the levels of GSH in trichloroacetic acid (TCA)-treated or untreated samples of rat plasma. It was found that the deproteinization of samples with TCA improved the electrochemical detection of GSH particularly in plasma. The oxidation of GSH was measured by using differential pulse voltammetry (DPV) method in combination with MWCNT-SPE (n=3), and the detection limit of GSH was found to be 0.47 µM (S/N=3). The GSH levels in plasma samples were also measured spectrophotometrically in order to compare the effectiveness of electrochemical method and we obtained a high correlation between the two methods (R(2)=0.976).

Thermochemical storage for CSP via redox structured reactors/heat exchangers: The RESTRUCTURE project

Science.gov (United States)

Karagiannakis, George; Pagkoura, Chrysoula; Konstandopoulos, Athanasios G.; Tescari, Stefania; Singh, Abhishek; Roeb, Martin; Lange, Matthias; Marcher, Johnny; Jové, Aleix; Prieto, Cristina; Rattenbury, Michael; Chasiotis, Andreas

2017-06-01

The present work provides an overview of activities performed in the framework of the EU-funded collaborative project RESTRUCTURE, the main goal of which was to develop and validate a compact structured reactor/heat exchanger for thermochemical storage driven by 2-step high temperature redox metal oxide cycles. The starting point of development path included redox materials qualification via both theoretical and lab-scale experimental studies. Most favorable compositions were cobalt oxide/alumina composites. Preparation of small-scale structured bodies included various approaches, ranging from perforated pellets to more sophisticated honeycomb geometries, fabricated by extrusion and coating. Proof-of-concept of the proposed novel reactor/heat exchanger was successfully validated in small-scale structures and the next step included scaling up of redox honeycombs production. Significant challenges were identified for the case of extruded full-size bodies and the final qualified approach related to preparation of cordierite substrates coated with cobalt oxide. The successful experimental evaluation of the pilot reactor/heat exchanger system constructed motivated the preliminary techno-economic evaluation of the proposed novel thermochemical energy storage concept. Taking into account experimental results, available technologies and standard design aspects a model for a 70.5 MWe CSP plant was defined. Estimated LCOE costs were calculated to be in the range of reference values for Combined Cycle Power Plants operated by natural gas. One of main cost contributors was the storage system itself, partially due to relatively high cost of cobalt oxide. This highlighted the need to identify less costly and equally efficient to cobalt oxide redox materials.

Hydrogen production via thermochemical water-splitting by lithium redox reaction

International Nuclear Information System (INIS)

Nakamura, Naoya; Miyaoka, Hiroki; Ichikawa, Takayuki; Kojima, Yoshitsugu

2013-01-01

Highlights: •Hydrogen production via water-splitting by lithium redox reactions possibly proceeds below 800 °C. •Entropy control by using nonequilibrium technique successfully reduces the reaction temperature. •The operating temperature should be further reduced by optimizing the nonequilibrium condition to control the cycle. -- Abstracts: Hydrogen production via thermochemical water-splitting by lithium redox reactions was investigated as energy conversion technique. The reaction system consists of three reactions, which are hydrogen generation by the reaction of lithium and lithium hydroxide, metal separation by thermolysis of lithium oxide, and oxygen generation by hydrolysis of lithium peroxide. The hydrogen generation reaction completed at 500 °C. The metal separation reaction is thermodynamically difficult because it requires about 3400 °C in equilibrium condition. However, it was indicated from experimental results that the reaction temperature was drastically reduced to 800 °C by using nonequilibrium technique. The hydrolysis reaction was exothermic reaction, and completed by heating up to 300 °C. Therefore, it was expected that the water-splitting by lithium redox reactions was possibly operated below 800 °C under nonequilibrium condition

Enhanced performance of ultracapacitors using redox additive-based electrolytes

Science.gov (United States)

Jain, Dharmendra; Kanungo, Jitendra; Tripathi, S. K.

2018-05-01

Different concentrations of potassium iodide (KI) as redox additive had been added to 1 M sulfuric acid (H2SO4) electrolyte with an aim of enhancing the capacitance and energy density of ultracapacitors via redox reactions at the interfaces of electrode-electrolyte. Ultracapacitors were fabricated using chemically treated activated carbon as electrode with H2SO4 and H2SO4-KI as an electrolyte. The electrochemical performances of fabricated supercapacitors were investigated by impedance spectroscopy, cyclic voltammetry and charge-discharge techniques. The maximum capacitance ` C' was observed with redox additives-based electrolyte system comprising 1 M H2SO4-0.3 M KI (1072 F g- 1), which is very much higher than conventional 1 M H2SO4 (61.3 F g- 1) aqueous electrolyte-based ultracapacitors. It corresponds to an energy density of 20.49 Wh kg- 1 at 2.1 A g- 1 for redox additive-based electrolyte, which is six times higher as compared to that of pristine electrolyte (1 M H2SO4) having energy density of only 3.36 Wh kg- 1. The temperature dependence behavior of fabricated cell was also analyzed, which shows increasing pattern in its capacitance values in a temperature range of 5-70 °C. Under cyclic stability test, redox electrolyte-based system shows almost 100% capacitance retention up to 5000 cycles and even more. For comparison, ultracapacitors based on polymer gel electrolyte polyvinyl alcohol (PVA) (10 wt%)—{H2SO4 (1 M)-KI (0.3 M)} (90 wt%) have been fabricated and characterized with the same electrode materials.

The influence of supplementation with artichoke (Cynara scolymus L.) extract on selected redox parameters in rowers.

Science.gov (United States)

Skarpanska-Stejnborn, Anna; Pilaczynska-Szczesniak, Lucia; Basta, Piotr; Deskur-Smielcka, Ewa; Horoszkiewicz-Hassan, Magorzata

2008-06-01

High-intensity physical exercise decreases intracellular antioxidant potential. An enhanced antioxidant defense system is desirable in people subjected to exhaustive exercise. The aim of this study was to investigate the influence of supplementation with artichoke-leaf extract on parameters describing balance between oxidants and antioxidants in competitive rowers. This double-blinded study was carried out in 22 members of the Polish rowing team who were randomly assigned to a supplemented group (n = 12), receiving 1 gelatin capsule containing 400 mg of artichoke-leaf extract 3 times a day for 5 wk, or a placebo group (n = 10). At the beginning and end of the study participants performed a 2,000-m maximal test on a rowing ergometer. Before each exercise test, 1 min after the test completion, and after a 24-hr restitution period blood samples were taken from antecubital vein. The following redox parameters were assessed in red blood cells: superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione levels, and thiobarbituric-acid-reactive-substances concentrations. Creatine kinase activity and total antioxidant capacity (TAC) were measured in plasma samples, lactate levels were determined in capillary blood samples, and serum lipid profiles were assessed. During restitution, plasma TAC was significantly higher (p artichoke-leaf extract, a natural vegetable preparation of high antioxidant potential, resulted in higher plasma TAC than placebo but did not limit oxidative damage to erythrocytes in competitive rowers subjected to strenuous training.

Prevention of redox shuttle using electropolymerized polypyrrole film in a lithium-oxygen battery

Science.gov (United States)

Togasaki, Norihiro; Shibamura, Ryuji; Naruse, Takuya; Momma, Toshiyuki; Osaka, Tetsuya

2018-04-01

Among the recent advancements in lithium-oxygen (Li-O2) chemistries, redox mediators (RMs) have been revealed to play a significant role in decreasing overpotential on charging and in improving cycling performance. However, an intrinsic problem is redox shuttle of RMs, which leads to degraded RM utilization and induces the accumulation of discharge products on the cathode surface; this remains a significant issue in the current battery cell configuration (Li anode/separator/cathode). To address this detrimental problem, herein we propose a novel Li-O2 cell incorporating a freestanding electropolymerized polypyrrole (PPy) film for the restriction of the redox-shuttle phenomenon of lithium iodide (Li anode/separator/PPy film/cathode). In this study, a PPy film, which is prepared through oxidative electropolymerization using an ionic liquid of 1-methyl-1-butylpyrrolidinium mixed with pyrrole and lithium bis(trifluoromethanesulfonyl)imide, is introduced between the cathode and the separator. From the charge-discharge voltage profile, it is confirmed that the PPy film suppresses the diffusion of the oxidized I3- to the Li anode, while allowing Li ion transport. Secondary scanning electron microscope measurements confirm that the chemical reactions between I3- and Li2O2 are facilitated by the presence of the PPy film because I3- remains near the cathode surface during the charging process. As a result, the cycling performance in the Li-O2 cells with PPy film exhibits a cycling life four times as long as that of the Li-O2 cells without PPy film.

Prevention of redox shuttle using electropolymerized polypyrrole film in a lithium–oxygen battery

Directory of Open Access Journals (Sweden)

Norihiro Togasaki

2018-04-01

Full Text Available Among the recent advancements in lithium–oxygen (Li–O2 chemistries, redox mediators (RMs have been revealed to play a significant role in decreasing overpotential on charging and in improving cycling performance. However, an intrinsic problem is redox shuttle of RMs, which leads to degraded RM utilization and induces the accumulation of discharge products on the cathode surface; this remains a significant issue in the current battery cell configuration (Li anode/separator/cathode. To address this detrimental problem, herein we propose a novel Li–O2 cell incorporating a freestanding electropolymerized polypyrrole (PPy film for the restriction of the redox-shuttle phenomenon of lithium iodide (Li anode/separator/PPy film/cathode. In this study, a PPy film, which is prepared through oxidative electropolymerization using an ionic liquid of 1-methyl-1-butylpyrrolidinium mixed with pyrrole and lithium bis(trifluoromethanesulfonylimide, is introduced between the cathode and the separator. From the charge–discharge voltage profile, it is confirmed that the PPy film suppresses the diffusion of the oxidized I3− to the Li anode, while allowing Li ion transport. Secondary scanning electron microscope measurements confirm that the chemical reactions between I3− and Li2O2 are facilitated by the presence of the PPy film because I3− remains near the cathode surface during the charging process. As a result, the cycling performance in the Li–O2 cells with PPy film exhibits a cycling life four times as long as that of the Li–O2 cells without PPy film.

Geochemistry of Natural Redox Fronts

International Nuclear Information System (INIS)

Hofmann, B.A.

1999-05-01

Redox fronts are important geochemical boundaries which need to be considered in safety assessment of deep repositories for radioactive waste. In most cases, selected host-rock formations will be reducing due to the presence of ferrous minerals, sulphides, etc. During construction and operation of the repository, air will be introduced into the formation. After repository closure, oxidising conditions may persist locally until all oxygen is consumed. In the case of high-level waste, radiolysis of water may provide an additional source of oxidants. Oxidising conditions within a repository are thus possible and potentially have a strong influence on the mobility of many elements. The rate of movement of redox fronts, the boundary between oxidising and reducing environments, and their influence on migrating radionuclides are thus important factors influencing repository performance. The present report is a review of elemental behaviour at natural redox fronts, based on published information and work of the author. Redox fronts are geochemically and geometrically variable manifestations of a global interface between generally oxidising geochemical milieux in contact with the atmosphere and generally reducing milieux in contact with rocks containing ferrous iron, sulphide and/or organic carbon. A classification of redox fronts based on a subdivision into continental near-surface, marine near-surface, and deep environments is proposed. The global redox interface is often located close to the surface of rocks and sediments and, sometimes, within bodies of water. Temperature conditions are close to ambient. A deeper penetration of the global redox front to depths of several kilometres is found in basins containing oxidised sediments (red beds) and in some hydrothermal circulation systems. Temperatures at such deep redox fronts may reach 200 o C. Both near-surface and deep redox fronts are sites of formation of economic deposits of redox-sensitive elements, particularly of

Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in caco-2 cells

NARCIS (Netherlands)

Usta, M.; Wortelboer, H.M.; Vervoort, J.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, P.J. van; Cnubben, N.H.P.

2007-01-01

Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and

Porphyrin-Based Symmetric Redox-Flow Batteries towards Cold-Climate Energy Storage.

Science.gov (United States)

Ma, Ting; Pan, Zeng; Miao, Licheng; Chen, Chengcheng; Han, Mo; Shang, Zhenfeng; Chen, Jun

2018-03-12

Electrochemical energy storage with redox-flow batteries (RFBs) under subzero temperature is of great significance for the use of renewable energy in cold regions. However, RFBs are generally used above 10 °C. Herein we present non-aqueous organic RFBs based on 5,10,15,20-tetraphenylporphyrin (H 2 TPP) as a bipolar redox-active material (anode: [H 2 TPP] 2- /H 2 TPP, cathode: H 2 TPP/[H 2 TPP] 2+ ) and a Y-zeolite-poly(vinylidene fluoride) (Y-PVDF) ion-selective membrane with high ionic conductivity as a separator. The constructed RFBs exhibit a high volumetric capacity of 8.72 Ah L -1 with a high voltage of 2.83 V and excellent cycling stability (capacity retention exceeding 99.98 % per cycle) in the temperature range between 20 and -40 °C. Our study highlights principles for the design of RFBs that operate at low temperatures, thus offering a promising approach to electrochemical energy storage under cold-climate conditions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Redox signaling in plants.