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Sample records for glutathione redox status

  1. 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.

  2. Investigation of a redox-sensitive predictive model of mouse embryonic stem cells differentiation using quantitative nuclease protection assays and glutathione redox status

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    Investigation of a redox-sensitive predictive model of mouse embryonic stem cell differentiation via quantitative nuclease protection assays and glutathione redox status Chandler KJ,Hansen JM, Knudsen T,and Hunter ES 1. U.S. Environmental Protection Agency, Research Triangl...

  3. Determination of Glutathione and Its Redox Status in Isolated Vacuoles of Red Beetroot Cells

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    E.V. Pradedova

    2016-02-01

    Full Text Available The glutathione of the red beetroot vacuoles (Beta vulgaris L. was measured using three well-known methods: the spectrofluorimetric method with orthophthalic aldehyde (OPT; the spectrophotometric method with 5.5'-dithiobis-2-nitrobenzoic acid (DTNB; the high-performance liquid chromatography (HPLC. The content of reduced (GSH and oxidized glutathione (GSSG differed depending on the research method. With OPT the concentration of glutathione was: GSH – 0.059 µmol /mg protein; GSSG – 0.019 µmol/mg protein and total glutathione (GSHtotal – 0.097 µmol/mg protein. In the case of determining with DTNB the concentration of glutathione was: GSH – 0.091 µmol/mg protein; GSSG – 0.031 µmol/mg protein; GSHtotal – 0.153 µmol/mg protein. HPLC-defined concentration of glutathione was lower: GSH – 0.039 µmol/mg protein; GSSG – 0.007 µmol/mg protein; GSHtotal – 0.053 µmol/mg protein. Redox ratio of GSH/GSSG was also dependent on the method of determination: with OPT – 3.11; with DTNB – 2.96 and HPLC – 5.57. Redox ratio of glutathione in vacuoles was much lower than the tissue extracts of red beetroot, which, depending on the method of determination, was: 7.23, 7.16 and 9.22. The results showed the vacuoles of red beetroot parenchyma cells contain glutathione. Despite the low value of the redox ratio GSH/GSSG, in vacuoles the pool of reduced glutathione prevailed over the pool of oxidized glutathione.

  4. 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

  5. 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.

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

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    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.

  7. 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.

  8. Glutathione Redox System in β-Thalassemia/Hb E Patients

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    Ruchaneekorn W. Kalpravidh

    2013-01-01

    Full Text Available β-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH/glutathione disulfide (GSSG and also to evaluate glutathione-related responses to oxidation in β-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 β-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body’s first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores.

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

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    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.

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

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    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...

  11. 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

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

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    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.

  13. 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.

  14. 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

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

    International Nuclear Information System (INIS)

    Anjum, Naser A.; Singh, Neetu; Singh, Manoj K.; Shah, Zahoor A.; Duarte, Armando C.; Pereira, Eduarda; Ahmad, Iqbal

    2013-01-01

    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 −1 ) of graphene oxide (0.5–5 μm) and evaluates glutathione (γ-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 −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 −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 glutathione

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  17. Garlic protects the glutathione redox cycle in irradiated rats

    International Nuclear Information System (INIS)

    Abu-Ghadeer, A.R.M.; Osman, S.A.A.; Abbady, M.M.

    1999-01-01

    The aim of the present study is to evaluate the possible radioprotective role of garlic oil on the glutathione redox cycle (GSH, GSH-Px, GR and G6-PD) in blood and tissues (liver, spleen and intestine) of irradiated rats. Garlic oil was orally administered to rats (100 mg/Kg- b.w.) for 7 days before exposure to a fractionated of whole body gamma irradiation up to 9 Gy (3 Gy X 3 at 2 days intervals) and during the whole period of irradiation. The data showed that radiation exposure caused significant inhibition of the biochemical parameters in blood and tissue of irradiated rats all over the investigation periods (3,7 and 15 days). Garlic oil ameliorated the decrease in the tested parameters with noticeable effect on the 15 Th. day after radiation exposure. It is concluded that garlic oil could control the radiation induced changes in the glutathione redox cycle and provided some radioprotective effect

  18. Glutathione redox potential in the mitochondrial intermembrane space is linked to the cytosol and impacts the Mia40 redox state

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    Kojer, Kerstin; Bien, Melanie; Gangel, Heike; Morgan, Bruce; Dick, Tobias P; Riemer, Jan

    2012-01-01

    Glutathione is an important mediator and regulator of cellular redox processes. Detailed knowledge of local glutathione redox potential (EGSH) dynamics is critical to understand the network of redox processes and their influence on cellular function. Using dynamic oxidant recovery assays together with EGSH-specific fluorescent reporters, we investigate the glutathione pools of the cytosol, mitochondrial matrix and intermembrane space (IMS). We demonstrate that the glutathione pools of IMS and cytosol are dynamically interconnected via porins. In contrast, no appreciable communication was observed between the glutathione pools of the IMS and matrix. By modulating redox pathways in the cytosol and IMS, we find that the cytosolic glutathione reductase system is the major determinant of EGSH in the IMS, thus explaining a steady-state EGSH in the IMS which is similar to the cytosol. Moreover, we show that the local EGSH contributes to the partially reduced redox state of the IMS oxidoreductase Mia40 in vivo. Taken together, we provide a comprehensive mechanistic picture of the IMS redox milieu and define the redox influences on Mia40 in living cells. PMID:22705944

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

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    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.

  20. 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.

  1. The role of Nrf1 and Nrf2 in the regulation of glutathione and redox dynamics in the developing zebrafish embryo

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    Karilyn E. Sant

    2017-10-01

    Full Text Available Redox signaling is important for embryogenesis, guiding pathways that govern processes crucial for embryo patterning, including cell polarization, proliferation, and apoptosis. Exposure to pro-oxidants during this period can be deleterious, resulting in altered physiology, teratogenesis, later-life diseases, or lethality. We previously reported that the glutathione antioxidant defense system becomes increasingly robust, including a doubling of total glutathione and dynamic shifts in the glutathione redox potential at specific stages during embryonic development in the zebrafish, Danio rerio. However, the mechanisms underlying these changes are unclear, as is the effectiveness of the glutathione system in ameliorating oxidative insults to the embryo at different stages. Here, we examine how the glutathione system responds to the model pro-oxidants tert-butylhydroperoxide and tert-butylhydroquinone at different developmental stages, and the role of Nuclear factor erythroid 2-related factor (Nrf proteins in regulating developmental glutathione redox status. Embryos became increasingly sensitive to pro-oxidants after 72 h post-fertilization (hpf, after which the duration of the recovery period for the glutathione redox potential was increased. To determine whether the doubling of glutathione or the dynamic changes in glutathione redox potential are mediated by zebrafish paralogs of Nrf transcription factors, morpholino oligonucleotides were used to knock down translation of Nrf1 and Nrf2 (nrf1a, nrf1b, nrf2a, nrf2b. Knockdown of Nrf1a or Nrf1b perturbed glutathione redox state until 72 hpf. Knockdown of Nrf2 paralogs also perturbed glutathione redox state but did not significantly affect the response of glutathione to pro-oxidants. Nrf1b morphants had decreased gene expression of glutathione synthesis enzymes, while hsp70 increased in Nrf2b morphants. This work demonstrates that despite having a more robust glutathione system, embryos become more

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

    Directory of Open Access Journals (Sweden)

    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

  3. 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

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  8. Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities

    Science.gov (United States)

    Jones, Dean P.; Brown, Lou Ann S.

    2012-01-01

    Abstract Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. Antioxid. Redox Signal. 17, 375–408. PMID:22304503

  9. Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle

    NARCIS (Netherlands)

    Le, C. T.; Hollaar, L.; van der Valk, E. J.; Franken, N. A.; van Ravels, F. J.; Wondergem, J.; van der Laarse, A.

    1995-01-01

    The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG),

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. 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

  16. Glutathione maintenance mitigates age-related susceptibility to redox cycling agents

    Directory of Open Access Journals (Sweden)

    Nicholas O. Thomas

    2016-12-01

    Full Text Available Isolated hepatocytes from young (4–6 mo and old (24–26 mo F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for young: 405 μM; LC50 for old: 275 μM. Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(PH: quinone oxido-reductase 1 (NQO1 protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3, but glutathione peroxidase 4 (GPX4 declined by 70% (p=0.0043; N=3. These results indicate toxicity may stem from vulnerability to lipid peroxidation instead of inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold higher, and GSH declined by a 3-fold greater margin in old versus young rat cells given 300 µM menadione (p2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated GSH-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    Science.gov (United States)

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

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

    Science.gov (United States)

    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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Optical imaging the redox status change during cell apoptosis

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    Su, Ting; Zhang, Zhihong; Lin, Juqiang; Luo, Qingming

    2007-02-01

    Many cellular events involve the alteration in redox equilibrium, globally or locally. In many cases, excessive reactive oxygen species (ROS) production is the underlying cause. Several green fluoresecence protein based indicators are constructed to measure redox status in cells, e.g, rxYFP and roGFPs, which allow real time detection. reduction and oxidization-sensitive GFP (RoGFPs) are more useful due to ratiometric variation by excitation, making the measurement more accurate. Utilizing one of those roGFPs called roGFP1, we establish a mitochondrial redox state probing platform in HeLa cells with laser scan confocal microscopy (LSCM) as detection system. Control experiments confirmed that our platform could produce stable ratiometric values, which made the data more accurately reflect the real environmental changes of redox status that roGFP1 probed. Using exogenous H IIO II and DTT, we evaluated the reactivity and reversibility of roGFP1. The minimal hydrogen peroxide concentration that roGFP1 could show detectable ratiometric changes in our system was about 200μM. Preliminarily applying our platform to exploring the redox status during apoptosis, we observed an increase in ratiometric, suggesting an excessive ROS production.

  5. 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.

  6. 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.

  7. A novel mitochondria-targeted two-photon fluorescent probe for dynamic and reversible detection of the redox cycles between peroxynitrite and glutathione.

    Science.gov (United States)

    Sun, Chunlong; Du, Wen; Wang, Peng; Wu, Yang; Wang, Baoqin; Wang, Jun; Xie, Wenjun

    2017-12-16

    Redox homeostasis is important for maintenance of normal physiological functions within cells. Redox state of cells is primarily a consequence of precise balance between levels of reducing equivalents and reactive oxygen species. Redox homeostasis between peroxynitrite (ONOO - ) and glutathione (GSH) is closely associated with physiological and pathological processes, such as prolonged relaxation in vascular tissues and smooth muscle preparations, attenuation of hepatic necrosis, and activation of matrix metalloproteinase-2. We report a two-photon fluorescent probe (TP-Se) based on water-soluble carbazole-based compound, which integrates with organic selenium, to monitor changes in ONOO - /GSH levels in cells. This probe can reversibly respond to ONOO - and GSH and exhibits high selectivity, sensitivity, and mitochondrial targeting. The probe was successfully applied to visualize changes in redox cycles during ONOO - outbreak and antioxidant GSH repair in cells. The probe will lead to significant development on redox events involved in cellular redox regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 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. 

  9. 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 +

  10. Glutathione in plants: an integrated overview.

    Science.gov (United States)

    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.

  11. Effect of an aqueous extract of Cucurbita ficifolia Bouché on the glutathione redox cycle in mice with STZ-induced diabetes.

    Science.gov (United States)

    Díaz-Flores, M; Angeles-Mejia, S; Baiza-Gutman, L A; Medina-Navarro, R; Hernández-Saavedra, D; Ortega-Camarillo, C; Roman-Ramos, R; Cruz, M; Alarcon-Aguilar, F J

    2012-10-31

    Cucurbita ficifolia is used in Mexican traditional medicine as an anti-diabetic and anti-inflammatory agent and its actions can be mediated by antioxidant mechanisms. Disturbance in the homeostasis of glutathione has been implicated in the etiology and progression of diabetes mellitus and its complications. It was evaluated, the effect of an aqueous extract of Cucurbita ficifolia on glycemia, plasma lipid peroxidation; as well as levels of reduced (GSH) and oxidized (GSSG) glutathione and activities of enzymes involved in glutathione redox cycle: glutathione peroxidase (GPx) and glutathione reductase (GR) in liver, pancreas, kidney and heart homogenates of streptozotocin-induced diabetic mice. Increased blood glucose and lipid peroxidation, together with decreased of GSH concentration, GSH/GSSG ratio and its redox potential (E(h)), and enhanced activity of GPx and GR in liver, pancreas and kidney were the salient features observed in diabetic mice. Administration of the aqueous extract of Cucurbita ficifolia to diabetic mice for 30 days, used at a dose of 200 mg/kg, resulted in a significant reduction in glycemia, polydipsia, hyperphagia and plasma lipid peroxidation. Moreover, GSH was increased in liver, pancreas and kidney, and GSSG was reduced in liver, pancreas and heart, therefore GSH/GSSG ratio and its E(h) were restored. Also, the activities involved in the glutathione cycle were decreased, reaching similar values to controls. An aqueous extract of Cucurbita ficifolia with hypoglycemic action, improve GSH redox state, increasing glutathione pool, GSH, GSH/GSSG ratio and its E(h), mechanism that can explain, at least in part, its antioxidant properties, supporting its use as an alternative treatment for the control of diabetes mellitus, and prevent the induction of complications by oxidative stress. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. 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.

  13. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.

    Science.gov (United States)

    Trivedi, Malav S; Holger, Dana; Bui, Anh Tuyet; Craddock, Travis J A; Tartar, Jaime L

    2017-01-01

    Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD) in young adult humans can influence systemic (plasma-derived) redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09) underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's sleep deprivation (maintaining wakefulness) uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  14. 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.

  15. Redox-based Epigenetic status in Drug Addiction: Potential mediator of drug-induced gene priming phenomenon and use of metabolic intervention for symptomatic treatment in drug addiction.

    Directory of Open Access Journals (Sweden)

    Malav Suchin Trivedi

    2015-01-01

    Full Text Available 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 the major epigenetic mechanism and it is one of more than 200 methylation reactions supported by methyl donor S-adenosylmethionine (SAM. The 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 transsulfuration pathway. Alcohol, dopamine and morphine, can alter intracellular levels of glutathione (GSH-based cellular redox status, subsequently affecting S-adenosylmethionine (SAM levels and DNA methylation status. In this discussion, we compile this and other existing evidence in a coherent manner to present a novel hypothesis implicating the involvement of redox-based epigenetic changes in drug addiction. Next, we also discuss how gene priming phenomenon can contribute to maintenance of redox and methylation status homeostasis under various stimuli including drugs of abuse. Lastly, based on our hypothesis and some preliminary evidence, we discuss a mechanistic explanation for use of metabolic interventions / redox-replenishers as symptomatic treatment of alcohol addiction and associated withdrawal symptoms. Hence, the current review article strengthens the hypothesis that neuronal metabolism has a critical bidirectional coupling with epigenetic changes in drug addiction and we support this claim via exemplifying the link between redox-based metabolic changes and resultant epigenetic consequences under the effect of drugs of abuse.

  16. Role of glutathione redox cycle and catalase in defense against oxidative stress induced by endosulfan in adrenocortical cells of rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Dorval, J.; Hontela, A.

    2003-01-01

    The role of antioxidants in maintaining the functional integrity of adrenocortical cells during in vitro exposure to endosulfan, an organochlorine pesticide, was investigated in rainbow trout (Oncorhynchus mykiss). Aminotriazole (ATA), an inhibitor of catalase (CAT), L-buthionine sulfoximine (L-BSO), an inhibitor of glutathione (GSH) synthesis, and N-acetyl cysteine (NAC), a glutathione precursor, were used to investigate the role of CAT and GSH redox cycle in protection against the adrenal toxicity of endosulfan, a pesticide that impairs cell viability (LC 50 366 μM) and cortisol secretion (EC 50 19 μM) in a concentration-related manner. Pretreatment with ATA and L-BSO enhanced the toxicity of endosulfan (LC 50 and EC 50 , respectively, 302 and 2.6 μM with ATA, 346 and 3.1 μM with L-BSO), while pretreatment with NAC had no significant effect on cell viability and increased the EC 50 of endosulfan to 51 μM. CAT activity was significantly reduced following exposure to endosulfan when cells were pretreated with ATA. Pretreatment with L-BSO significantly decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels in a concentration-related manner following exposure to endosulfan, while GSH levels were significantly higher in NAC pretreated cells compared to untreated cells. Finally, pretreatment with ATA and L-BSO increased, while pretreatment with NAC decreased, lipid hydroperoxides (LOOH) levels. CAT, GPx, and GSH were identified as important antioxidants in maintaining the function and integrity of rainbow trout adrenocortical cells and ATA, L-BSO, and NAC were identified as effective modulators of CAT and GSH redox cycle. Moreover, this study suggests that the glutathione redox cycle may be more efficient than catalase in protecting adrenocortical cells against endosulfan-induced oxidative stress

  17. Analysis of redox relationships in the plant cell cycle: determinations of ascorbate, glutathione and poly (ADPribose)polymerase (PARP) in plant cell cultures.

    Science.gov (United States)

    Foyer, Christine H; Pellny, Till K; Locato, Vittoria; De Gara, Laura

    2008-01-01

    Reactive oxygen species (ROS) and low molecular weight antioxidants, such as glutathione and ascorbate, are powerful signaling molecules that participate in the control of plant growth and development, and modulate progression through the mitotic cell cycle. Enhanced reactive oxygen species accumulation or low levels of ascorbate or glutathione cause the cell cycle to arrest and halt progression especially through the G1 checkpoint. Plant cell suspension cultures have proved to be particularly useful tools for the study of cell cycle regulation. Here we provide effective and accurate methods for the measurement of changes in the cellular ascorbate and glutathione pools and the activities of related enzymes such poly (ADP-ribose) polymerase during mitosis and cell expansion, particularly in cell suspension cultures. These methods can be used in studies seeking to improve current understanding of the roles of redox controls on cell division and cell expansion.

  18. Current status and emerging role of glutathione in food grade lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Pophaly Sarang

    2012-08-01

    Full Text Available Abstract Lactic acid bacteria (LAB have taken centre stage in perspectives of modern fermented food industry and probiotic based therapeutics. These bacteria encounter various stress conditions during industrial processing or in the gastrointestinal environment. Such conditions are overcome by complex molecular assemblies capable of synthesizing and/or metabolizing molecules that play a specific role in stress adaptation. Thiols are important class of molecules which contribute towards stress management in cell. Glutathione, a low molecular weight thiol antioxidant distributed widely in eukaryotes and Gram negative organisms, is present sporadically in Gram positive bacteria. However, new insights on its occurrence and role in the latter group are coming to light. Some LAB and closely related Gram positive organisms are proposed to possess glutathione synthesis and/or utilization machinery. Also, supplementation of glutathione in food grade LAB is gaining attention for its role in stress protection and as a nutrient and sulfur source. Owing to the immense benefits of glutathione, its release by probiotic bacteria could also find important applications in health improvement. This review presents our current understanding about the status of glutathione and its role as an exogenously added molecule in food grade LAB and closely related organisms.

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

    Science.gov (United States)

    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.

  20. 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.

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

    Science.gov (United States)

    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.

  2. 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.

  3. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.

    Directory of Open Access Journals (Sweden)

    Malav S Trivedi

    Full Text Available Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD in young adult humans can influence systemic (plasma-derived redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09 underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's < 0.01. Parallel to the well-recognized fact that sleep deprivation (maintaining wakefulness uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  4. Effects of commonly consumed fruit juices and carbohydrates on redox status and anticancer biomarkers in female rats

    DEFF Research Database (Denmark)

    Breinholt, Vibeke M.; Nielsen, Salka E.; Knuthsen, Pia

    2003-01-01

    /kg of diet. However, no effects were observed on hepatic glutathione S-transferase or quinone reductase activities, plasma redox status, or the activity of red blood cell antioxidant enzymes. Overall, the results of the present study suggest that commonly consumed fruit juices can alter lipid and protein......Administration of apple juice, black currant juice, ora 1:1 combination of the two juices significantly decreased the level of the lipid peroxidation biomarker malondialdehyde in plasma of female rats, whereas the protein oxidation biomarker 2-amino-adipic semialdehyde, was significantly increased...... following administration of orange juice, black currant juice, or the 1: 1 combination of apple and black currant juice. A significant increase in 2-amino-adipic semialdehyde was also observed in control rats given sucrose, fructose, and glucose in the drinking water at concentrations approximating...

  5. Cytotoxicity of Cerastes cerastes snake venom: Involvement of imbalanced redox status.

    Science.gov (United States)

    Kebir-Chelghoum, Hayet; Laraba-Djebari, Fatima

    2017-09-01

    Envenomation caused by Cerastes cerastes snake venom is characterized by a local and a systemic tissue damage due to myonecrosis, hemorrhage, edema and acute muscle damage. The present study aimed to evaluate the relationship between the pro/anti-oxidants status and the cytotoxicity of C. cerastes snake venom. The in vivo cytotoxicity analysis was undertaken by the injection of C. cerastes venom (48μg/20g body weight) by i.p. route, mice were then sacrificed at 3, 24 and 48h post injection, organs were collected for further analysis. In vitro cytotoxicity analysis was investigated on cultured PBMC, hepatocytes and isolated liver. The obtained results showed a significant cell infiltration characterized by a significant increase of myeloperoxidase (MPO) and eosinoperoxidase (EPO) activities. These results showed also a potent oxidative activity of C. cerastes venom characterized by increased levels of residual nitrites and lipid peroxidation associated with a significant decrease of glutathione and catalase activity in sera and tissues (heart, lungs, liver and kidneys). The in vitro cytotoxicity of C. cerastes venom on PBMC seems to be dose-dependent (IC50 of 21μg/ml/10 6 cells) and correlated with an imbalanced redox status at high doses of venom. However, in the case of cultured hepatocytes, the LDH release and oxidative stress were observed only at high doses of the venom. The obtained results of in vivo study were confirmed by the culture of isolated liver. Therefore, these results suggest that the venom induces a direct cytotoxic effect which alters the membrane integrity causing a leakage of the cellular contents. This cytotoxic effect can lead indirectly to inflammatory response and oxidative stress. These data suggest that an early anti-inflammatory and antioxidant treatment could be useful in the management of envenomed victims. Copyright © 2017. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Pyridine nucleotide cycling and control of intracellular redox state in relation to poly (ADP-ribose) polymerase activity and nuclear localization of glutathione during exponential growth of Arabidopsis cells in culture.

    Science.gov (United States)

    Pellny, Till K; Locato, Vittoria; Vivancos, Pedro Diaz; Markovic, Jelena; De Gara, Laura; Pallardó, Federico V; Foyer, Christine H

    2009-05-01

    Pyridine nucleotides, ascorbate and glutathione are major redox metabolites in plant cells, with specific roles in cellular redox homeostasis and the regulation of the cell cycle. However, the regulation of these metabolite pools during exponential growth and their precise functions in the cell cycle remain to be characterized. The present analysis of the abundance of ascorbate, glutathione, and pyridine nucleotides during exponential growth of Arabidopsis cells in culture provides evidence for the differential regulation of each of these redox pools. Ascorbate was most abundant early in the growth cycle, but glutathione was low at this point. The cellular ascorbate to dehydroascorbate and reduced glutathione (GSH) to glutathione disulphide ratios were high and constant but the pyridine nucleotide pools were largely oxidized over the period of exponential growth and only became more reduced once growth had ceased. The glutathione pool increased in parallel with poly (ADP-ribose) polymerase (PARP) activities and with increases in the abundance of PARP1 and PARP2 mRNAs at a time of high cell cycle activity as indicated by transcriptome information. Marked changes in the intracellular partitioning of GSH between the cytoplasm and nucleus were observed. Extension of the exponential growth phase by dilution or changing the media led to increases in the glutathione and nicotinamide adenine dinucleotide, oxidized form (NAD)-plus-nicotinamide adenine dinucleotide, reduced form (NADH) pools and to higher NAD/NADH ratios but the nicotinamide adenine dinucleotide phosphate, oxidized form (NADP)-plus-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) pool sizes, and NAPD/NADPH ratios were much less affected. The ascorbate, glutathione, and pyridine nucleotide pools and PARP activity decreased before the exponential growth phase ended. We conclude that there are marked changes in intracellular redox state during the growth cycle but that redox homeostasis is

  8. 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

  9. 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...

  10. EFFECT OF THIOPROPANOL ON AMINO ACID TURNOVER AND REDOX STATUS IN ALLOXAN DIABETIC RAT LIVER

    Directory of Open Access Journals (Sweden)

    Vickram

    2016-07-01

    Full Text Available BACKGROUND Decreased cellular thiol levels seen in diabetes mellitus (DM may be in part attributed to increased free radical generation. The free radical mediated oxidative stress has been implicated in the pathogenesis of DM and its complications. The relative deficiency or non-availability of insulin in DM affects the metabolism of biomolecules, specifically the carbohydrate metabolism. The insulin-mimicking actions of various thiols have been studied. In our previous study, we have documented that 3-mercapto- 1-propanol (Thiopropanol, a low molecular weight thiol, at the dosage employed has increased glucose utilisation in alloxandiabetic rat liver tissue probably by favouring utilisation of glucose through glycolysis and HMP pathway. It is known that insulin inhibits gluconeogenesis by inhibiting the key enzymes of the same and by controlling the channelling of amino acids for the glucose biosynthesis through gluconeogenic pathway. A study was undertaken to assess the effects of thiopropanol (TP on amino acid turnover and the redox status in alloxan diabetic rat liver. METHODS Male albino rats weighing 150-250 g were used. Diabetes was induced using alloxan monohydrate. Rats were divided into normal and diabetic groups. Levels of amino acid nitrogen (AAN, alanine, total thiol (-SH groups, TBARS (Thiobarbituric acid reactive substances, and activities of alanine transaminase (ALT and aspartate transaminase (AST were estimated in liver specimens of normal, control-alloxan diabetic and TP-exposed-alloxan-diabetic rats. RESULTS The results showed a significant increase (p<0.001 in AAN levels, alanine levels, and total -SH groups concentration; and a significant decrease (p<0.001 in TBARS levels, ALT and AST activities in TP-exposed-alloxan diabetic liver slices as compared to control-alloxan diabetic liver slices. CONCLUSIONS Hence, it may be concluded that TP, at the concentration employed, inhibits gluconeogenesis from amino acids probably by

  11. Direct determination of the redox status of cysteine residues in proteins in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Satoshi [Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503 (Japan); Tatenaka, Yuki; Ohuchi, Yuya [Dojindo Laboratories, 2025-5 Tabaru, Mashiki-machi, Kumamoto 861-2202 (Japan); Hisabori, Toru, E-mail: thisabor@res.titech.ac.jp [Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503 (Japan); Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075 (Japan)

    2015-01-02

    Highlights: • A new DNA-maleimide which is cleaved by UV irradiation, DNA-PCMal, was developed. • DNA-PCMal can be used like DNA-Mal to analyze the redox state of cysteine residues. • It is useful for detecting the thiol redox status of a protein in vivo by Western blotting method. • Thus, DNA-PCMal can be a powerful tool for redox proteomics analysis. - Abstract: The redox states of proteins in cells are key factors in many cellular processes. To determine the redox status of cysteinyl thiol groups in proteins in vivo, we developed a new maleimide reagent, a photocleavable maleimide-conjugated single stranded DNA (DNA-PCMal). The DNA moiety of DNA-PCMal is easily removed by UV-irradiation, allowing DNA-PCMal to be used in Western blotting applications. Thereby the state of thiol groups in intracellular proteins can be directly evaluated. This new maleimide compound can provide information concerning redox proteins in vivo, which is important for our understanding of redox networks in the cell.

  12. 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

  13. 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

  14. 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

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

    Science.gov (United States)

    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.

  16. 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.

  17. Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

    Directory of Open Access Journals (Sweden)

    S.F. Fonseca

    2016-03-01

    Full Text Available Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H and 8 normotensive (N subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively. They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity. Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS levels and ferric reducing ability of plasma (FRAP. Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05, although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1 and lower TBARS (P<0.01 and FRAP (P<0.05 levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors, present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

  18. Ursolic Acid-enriched herba cynomorii extract induces mitochondrial uncoupling and glutathione redox cycling through mitochondrial reactive oxygen species generation: protection against menadione cytotoxicity in h9c2 cells.

    Science.gov (United States)

    Chen, Jihang; Wong, Hoi Shan; Ko, Kam Ming

    2014-01-27

    Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used 'Yang-invigorating' tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

  19. Zinc and the modulation of redox homeostasis

    Science.gov (United States)

    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

  20. Organophosphate pesticides-induced changes in the redox status of rat tissues and protective effects of antioxidant vitamins.

    Science.gov (United States)

    Mishra, Vibhuti; Srivastava, Nalini

    2015-04-01

    Organophosphates (OPs) pesticides are among the most toxic synthetic chemicals purposefully added in the environment. The common use of OP insecticides in public health and agriculture results in an environmental pollution and a number of acute and chronic poisoning events. Present study was aimed to evaluate the potential of monocrotophos and quinalphos to effect the redox status and glutathione (GSH) homeostasis in rat tissues and find out whether antioxidant vitamins have some protection on the pesticide-induced alterations. The results showed that these pesticides alone or in combination, caused decrease in the levels of GSH and the corresponding increase in the levels of GSSG, decreasing the GSH/GSSG ratio. The results also showed that NADPH/NADP(+) and NADH/NAD(+) ratios were decreased in the liver and brain of rats on exposure with mococrotophos, quinalphos, and their mixture. These pesticides, alone or in combination, caused alterations in the activities of GSH reductase and glucose-6-phosphate dehydrogenase in the rat tissues. However, the expression of the GSH recycling enzymes did not show significant alterations as compared to control. From the results, it can be concluded that these pesticides generate oxidative stress but their effects were not synergistic when given together and prior feeding of antioxidant vitamins tend to reduce the toxicities of these pesticides. Copyright © 2013 Wiley Periodicals, Inc.

  1. Novel feed including bioactive compounds from winery wastes improved broilers' redox status in blood and tissues of vital organs.

    Science.gov (United States)

    Makri, Sotiria; Kafantaris, Ioannis; Stagos, Dimitrios; Chamokeridou, Theodora; Petrotos, Konstantinos; Gerasopoulos, Konstantinos; Mpesios, Anastasios; Goutzourelas, Nikolaos; Kokkas, Stylianos; Goulas, Panagiotis; Komiotis, Dimitrios; Kouretas, Dimitrios

    2017-04-01

    Currently, there is a great interest in the production of animal feed with antioxidant activity. The aim of this study was to examine the potential antioxidant effects of a feed supplemented with grape pomace (GP), a winery by-product with high environmental load, in chickens. Broilers of 15 days post birth were separated into two groups fed either with standard diet or with diet supplemented with GP for 35 days. Blood and tissues collections were performed after feeding for 15 and 35 days with the experimental diet (i.e. at 30 and 50 days post birth). Free radical toxicity markers, namely thiobarbituric acid reactive substances, protein carbonyls, total antioxidant capacity, reduced glutathione, catalase activity and rate of H 2 O 2 decomposition were determined in blood and tissues of vital organs. The results indicated that feed supplemented with GP decreased oxidative stress-induced toxic effects and improved chickens' redox status, and so it may also improve their wellness and productivity. On the other hand, this exploitation of GP may solve problems of environmental pollution in areas with wineries. Copyright © 2017. Published by Elsevier Ltd.

  2. Redox status evaluation in dogs affected by mast cell tumour.

    Science.gov (United States)

    Finotello, R; Pasquini, A; Meucci, V; Lippi, I; Rota, A; Guidi, G; Marchetti, V

    2014-06-01

    Oxidative stress status has been evaluated in depth in human medicine and its role in carcinogenesis has been clearly established. The purpose of this prospective study was to evaluate antioxidant concentrations and oxidative stress in dogs with mast cell tumours (MCTs) that had received no previous treatments, and to compare them to healthy controls. In 23 dogs with mast cell tumour and 10 healthy controls, oxidative status was assessed using the Reactive Oxygen Metabolites-derived compounds (d-ROMs) test, antioxidant activity was measured by the Biological Antioxidant Potential (BAP) test, and α-tocopherol levels were evaluated using high-performance liquid chromatography and ultraviolet analysis. At baseline, dogs with MCT had significantly higher d-ROMs (P defence barrier are altered in dogs with newly diagnosed MCT compared with control dogs. Future studies are needed in order to assess the prognostic role of oxidative stress and to evaluate the impact of different therapeutic approaches. © 2012 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Iron Supplementation Effects on Redox Status following Aseptic Skeletal Muscle Trauma in Adults and Children

    Directory of Open Access Journals (Sweden)

    Chariklia K. Deli

    2017-01-01

    Full Text Available Exercise-induced skeletal muscle microtrauma is characterized by loss of muscle cell integrity, marked aseptic inflammatory response, and oxidative stress. We examined if iron supplementation would alter redox status after eccentric exercise. In a randomized, double blind crossover study, that was conducted in two cycles, healthy adults (n=14 and children (n=11 received daily either 37 mg of elemental iron or placebo for 3 weeks prior to and up to 72 h after an acute eccentric exercise bout. Blood was drawn at baseline, before exercise, and 72 h after exercise for the assessment of iron status, creatine kinase activity (CK, and redox status. Iron supplementation at rest increased iron concentration and transferrin saturation (p<0.01. In adults, CK activity increased at 72 h after exercise, while no changes occurred in children. Iron supplementation increased TBARS at 72 h after exercise in both adults and children; no changes occurred under placebo condition. Eccentric exercise decreased bilirubin concentration at 72 h in all groups. Iron supplementation can alter redox responses after muscle-damaging exercise in both adults and children. This could be of great importance not only for healthy exercising individuals, but also in clinical conditions which are characterized by skeletal muscle injury and inflammation, yet iron supplementation is crucial for maintaining iron homeostasis. This study was registered at Clinicaltrials.gov Identifier: NCT02374619.

  5. Iron Supplementation Effects on Redox Status following Aseptic Skeletal Muscle Trauma in Adults and Children.

    Science.gov (United States)

    Deli, Chariklia K; Fatouros, Ioannis G; Paschalis, Vassilis; Tsiokanos, Athanasios; Georgakouli, Kalliopi; Zalavras, Athanasios; Avloniti, Alexandra; Koutedakis, Yiannis; Jamurtas, Athanasios Z

    2017-01-01

    Exercise-induced skeletal muscle microtrauma is characterized by loss of muscle cell integrity, marked aseptic inflammatory response, and oxidative stress. We examined if iron supplementation would alter redox status after eccentric exercise. In a randomized, double blind crossover study, that was conducted in two cycles, healthy adults ( n = 14) and children ( n = 11) received daily either 37 mg of elemental iron or placebo for 3 weeks prior to and up to 72 h after an acute eccentric exercise bout. Blood was drawn at baseline, before exercise, and 72 h after exercise for the assessment of iron status, creatine kinase activity (CK), and redox status. Iron supplementation at rest increased iron concentration and transferrin saturation ( p exercise, while no changes occurred in children. Iron supplementation increased TBARS at 72 h after exercise in both adults and children; no changes occurred under placebo condition. Eccentric exercise decreased bilirubin concentration at 72 h in all groups. Iron supplementation can alter redox responses after muscle-damaging exercise in both adults and children. This could be of great importance not only for healthy exercising individuals, but also in clinical conditions which are characterized by skeletal muscle injury and inflammation, yet iron supplementation is crucial for maintaining iron homeostasis. This study was registered at Clinicaltrials.gov Identifier: NCT02374619.

  6. Effects of exogenous vitamins A, C, and E and NADH supplementation on proliferation, cytokines release, and cell redox status of lymphocytes from healthy aged subjects.

    Science.gov (United States)

    Bouamama, Samia; Merzouk, Hafida; Medjdoub, Amel; Merzouk-Saidi, Amel; Merzouk, Sid Ahmed

    2017-06-01

    Aging is an inevitable biological event that is associated with immune alterations. These alterations are related to increased cellular oxidative stress and micronutrient deficiency. Antioxidant supplementation could improve these age-related abnormalities. The aim of this study was to determine in vitro effects of vitamin A, vitamin C, vitamin E, and nicotinamide adenine dinucleotide (NADH) on T cell proliferation, cytokine release, and cell redox status in the elderly compared with young adults. Peripheral blood lymphocytes were isolated using a density gradient of Histopaque. They were cultured in vitro and stimulated with concanavalin A in the presence or absence of vitamins. Cell proliferation was determined by conducting MTT assays, and based on interleukin-2 and interleukin-4 secretions. Cell oxidant/antioxidant balance was assessed by assaying reduced glutathione (GSH), malondialdehyde, carbonyl protein levels, and catalase activity. The present study demonstrated that T-lymphocyte proliferation was decreased with aging and was associated with cytokine secretion alterations, GSH depletion, and intracellular oxidative stress. In the elderly, vitamin C, vitamin E, and NADH significantly improved lymphocyte proliferation and mitigated cellular oxidative stress, whereas vitamin A did not affect cell proliferation or cell redox status. In conclusion, vitamin C, vitamin E, and NADH supplementation improved T-lymphocytes response in the elderly, and could contribute to the prevention of age-related immune alterations. Consumption of food items containing these vitamins is recommended, and further investigation is necessary to evaluate the effect of vitamin supplementation in vivo.

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

    Science.gov (United States)

    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.

  8. Treatment of chronic hemodialysis patients with low-dose fenofibrate effectively reduces plasma lipids and affects plasma redox status

    Directory of Open Access Journals (Sweden)

    Makówka Agnieszka

    2012-07-01

    Full Text Available Abstract Dyslipidemia is common in chronic hemodialysis patients and its underlying mechanism is complex. Hemodialysis causes an imbalance between antioxidants and production of reactive oxygen species, which induces the oxidative stress and thereby may lead to accelerated atherosclerosis. Statins have been found to be little effective in end-stage kidney disease and other lipid-lowering therapies have been only scarcely studied. The study aimed to assess the effect of low-dose fenofibrate therapy on plasma lipids and redox status in long-term hemodialysis patients with mild hypertriglyceridemia. Twenty seven chronic hemodialysis patients without any lipid-lowering therapy were included in a double-blind crossover, placebo-controlled study. The patients were randomized into two groups and were given a sequence of either 100 mg of fenofibrate per each hemodialysis day for 4 weeks or placebo with a week-long wash-out period between treatment periods. Plasma lipids, high sensitive C-reactive protein (CRP, urea, creatinine, electrolytes, phosphocreatine kinase (CK, GOT, GPT and plasma thiols (total and free glutathione, homocysteine, cysteine and cysteinylglycine were measured at baseline and after each of the study periods. Plasma aminothiols were measured by reversed phase HPLC with thiol derivatization with 2-chloro-1-methylquinolinium tetrafluoroborate. Fenofibrate therapy caused a significant decrease of total serum cholesterol, LDL cholesterol and triglycerides and an increase of HDL cholesterol. The treatment was well tolerated with no side-effects but there was a small but significant increase of CK not exceeding the upper limit of normal range. There were no changes of serum CRP, potassium, urea, and creatinine and liver enzymes during the treatment. Neither total nor total free cysteinylglycine and cysteine changed during the study but both total and free glutathione increased during the therapy with fenofibrate and the same was observed

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

    Science.gov (United States)

    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

  10. Overview of the Role of Vanillin on Redox Status and Cancer Development

    Science.gov (United States)

    Bezerra, Daniel Pereira; Soares, Anne Karine Nascimento

    2016-01-01

    Bioactive natural products play critical roles in modern drug development, especially anticancer agents. It has been widely reported that various pharmacological activities of such compounds are related to their antioxidant properties. Vanillin is a natural substance widely found in many plant species and often used in beverages, foods, cosmetics, and pharmaceutical products. Antioxidant and anticancer potential have been described for this compound. Considering the importance of vanillin in the area of human health and food and pharmaceuticals sectors, in this review, we discuss the role of vanillin on redox status and its potential contribution to the prevention and the treatment of cancer. PMID:28077989

  11. Overview of the Role of Vanillin on Redox Status and Cancer Development

    Directory of Open Access Journals (Sweden)

    Daniel Pereira Bezerra

    2016-01-01

    Full Text Available Bioactive natural products play critical roles in modern drug development, especially anticancer agents. It has been widely reported that various pharmacological activities of such compounds are related to their antioxidant properties. Vanillin is a natural substance widely found in many plant species and often used in beverages, foods, cosmetics, and pharmaceutical products. Antioxidant and anticancer potential have been described for this compound. Considering the importance of vanillin in the area of human health and food and pharmaceuticals sectors, in this review, we discuss the role of vanillin on redox status and its potential contribution to the prevention and the treatment of cancer.

  12. Redox status affects the catalytic activity of glutamyl-tRNA synthetase

    DEFF Research Database (Denmark)

    Katz, Assaf; Banerjee, Rajat; de Armas, Merly

    2010-01-01

    Glutamyl-tRNA synthetases (GluRS) provide Glu-tRNA for different processes including protein synthesis, glutamine transamidation and tetrapyrrole biosynthesis. Many organisms contain multiple GluRSs, but whether these duplications solely broaden tRNA specificity or also play additional roles in t...... inactivation by hemin plus hydrogen peroxide. The sensitivity to oxidation of A. ferrooxidans GluRS1 might provide a means to regulate tetrapyrrole and protein biosynthesis in response to extreme changes in both the redox and heme status of the cell via a single enzyme....

  13. Proliferation and differentiation of Trypanosoma cruzi inside its vector have a new trigger: redox status.

    Directory of Open Access Journals (Sweden)

    Natália P Nogueira

    Full Text Available Trypanosoma cruzi proliferate and differentiate inside different compartments of triatomines gut that is the first environment encountered by T. cruzi. Due to its complex life cycle, the parasite is constantly exposed to reactive oxygen species (ROS. We tested the influence of the pro-oxidant molecules H2O2 and the superoxide generator, Paraquat, as well as, metabolism products of the vector, with distinct redox status, in the proliferation and metacyclogenesis. These molecules are heme, hemozoin and urate. We also tested the antioxidants NAC and GSH. Heme induced the proliferation of epimastigotes and impaired the metacyclogenesis. β-hematin, did not affect epimastigote proliferation but decreased parasite differentiation. Conversely, we show that urate, GSH and NAC dramatically impaired epimastigote proliferation and during metacyclogenesis, NAC and urate induced a significant increment of trypomastigotes and decreased the percentage of epimastigotes. We also quantified the parasite loads in the anterior and posterior midguts and in the rectum of the vector by qPCR. The treatment with the antioxidants increased the parasite loads in all midgut sections analyzed. In vivo, the group of vectors fed with reduced molecules showed an increment of trypomastigotes and decreased epimastigotes when analyzed by differential counting. Heme stimulated proliferation by increasing the cell number in the S and G2/M phases, whereas NAC arrested epimastigotes in G1 phase. NAC greatly increased the percentage of trypomastigotes. Taken together, these data show a shift in the triatomine gut microenvironment caused by the redox status may also influence T. cruzi biology inside the vector. In this scenario, oxidants act to turn on epimastigote proliferation while antioxidants seem to switch the cycle towards metacyclogenesis. This is a new insight that defines a key role for redox metabolism in governing the parasitic life cycle.

  14. Oxidative actions of hydrogen peroxide in human gingival and oral periosteal fibroblasts: Responses to glutathione and nicotine, relevant to healing in a redox environment

    Directory of Open Access Journals (Sweden)

    Federico Tinti

    2014-01-01

    Conclusion: Oxidative stress mediated by H2O2 was overcome by glutathione and recurred when nicotine was added, suggestive of a pro- oxidant role for nicotine. Androgen biomarkers are a sensitive index of oxidative stress which affects wound healing.

  15. Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX system increase the level of indole-3-acetic acid, gibberellin A3 and trans-zeatin in Eucalyptus globulus trees.

    Science.gov (United States)

    González, Alberto; Contreras, Rodrigo A; Zúiga, Gustavo; Moenne, Alejandra

    2014-08-20

    Eucalyptus globulus trees treated with oligo-carrageenan (OC) kappa showed an increase in NADPH, ascorbate and glutathione levels and activation of the thioredoxin reductase (TRR)/thioredoxin (TRX) system which enhance photosynthesis, basal metabolism and growth. In order to analyze whether the reducing redox status and the activation of thioredoxin reductase (TRR)/thioredoxin (TRX) increased the level of growth-promoting hormones, trees were treated with water (control), with OC kappa, or with inhibitors of ascorbate synthesis, lycorine, glutathione synthesis, buthionine sulfoximine (BSO), NADPH synthesis, CHS-828, and thioredoxin reductase activity, auranofine, and with OC kappa, and cultivated for four additional months. Eucalyptus trees treated with OC kappa showed an increase in the levels of the auxin indole 3-acetic acid (IAA), gibberellin A3 (GA3) and the cytokinin trans-zeatin (t-Z) as well as a decrease in the level of the brassinosteroid epi-brassinolide (EB). In addition, treatment with lycorine, BSO, CHS-828 and auranofine inhibited the increase in IAA, GA3 and t-Z as well as the decrease in EB levels. Thus, the reducing redox status and the activation of TRR/TRX system induced by OC kappa increased the levels of IAA, GA3 and t-Z levels determining, at least in part, the stimulation of growth in Eucalyptus trees.

  16. Gene expression, glutathione status and indicators of hepatic oxidative stress in laughing gull (Larus atricilla) hatchlings exposed to methylmercury

    Science.gov (United States)

    Jenko, Kathryn; Karouna-Renier, Natalie K.; Hoffman, David J.

    2012-01-01

    Despite extensive studies of methylmercury (MeHg) toxicity in birds, molecular effects on birds are poorly characterized. To improve our understanding of toxicity pathways and identify novel indicators of avian exposure to Hg, the authors investigated genomic changes, glutathione status, and oxidative status indicators in liver from laughing gull (Larus atricilla) hatchlings that were exposed in ovo to MeHg (0.05–1.6 µg/g). Genes involved in the transsulfuration pathway, iron transport and storage, thyroid-hormone related processes, and cellular respiration were identified by suppression subtractive hybridization as differentially expressed. Quantitative polymerase chain reaction (qPCR) identified statistically significant effects of Hg on cytochrome C oxidase subunits I and II, transferrin, and methionine adenosyltransferase RNA expression. Glutathione-S-transferase activity and protein-bound sulfhydryl levels decreased, whereas glucose-6-phosphate dehydrogenase activity increased dose-dependently. Total sulfhydryl concentrations were significantly lower at 0.4 µg/g Hg than in controls. T ogether, these endpoints provided some evidence of compensatory effects, but little indication of oxidative damage at the tested doses, and suggest that sequestration of Hg through various pathways may be important for minimizing toxicity in laughing gulls. This is the first study to describe the genomic response of an avian species to Hg. Laughing gulls are among the less sensitive avian species with regard to Hg toxicity, and their ability to prevent hepatic oxidative stress may be important for surviving levels of MeHg exposures at which other species succumb.

  17. Mathematical modeling of glutathione status in type 2 diabetics with vitamin B12 deficiency

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    Varun eKaramshetty

    2016-03-01

    Full Text Available Deficiencies in vitamin B12 and glutathione (GSH are associated with anumber of diseases including type 2 diabetes mellitus. We tested newly diag-nosed Indian diabetic patients for correlation between their vitamin B12 andGSH, and found it to be weak. Here we seek to examine the theoreticaldependence of GSH on vitamin B12 with a mathematical model of 1-carbonmetabolism due to Reed and co-workers. We study the methionine cycleof the Reed-Nijhout model by developing a simple ‘stylized model’ that cap-tures its essential topology and whose kinetics are analytically tractable. Theanalysis shows – somewhat counter-intuitively – that the flux responsible forthe homeostasis of homocysteine is, in fact, peripheral to the methioninecycle. Elevation of homocysteine arises from reduced activity of methioninesynthase, a vitamin B12-dependent enzyme, however, this does not increaseGSH biosynthesis. The model suggests that the lack of vitamin B12–GSHcorrelation is explained by suppression of activity in the trans-sulfurationpathway that limits the synthesis of cysteine and GSH from homocysteine.We hypothesize this ‘cysteine-block’ is an essential consequence of vitaminB12 deficiency. It can be clinically relevant to appreciate that these secondaryeffects of vitamin B12 deficiency could be central to its pathophysiology.

  18. Clinical Assessment of glutathione peroxidase and catalase to the status of malondialdehyde in urolithiasis

    International Nuclear Information System (INIS)

    Mahmoud, R.H.; Ewadh, M.J.; Al-Hamadani, K.J.

    2010-01-01

    Objective: To assess the role of lipid peroxidation and antioxidant enzymes in serum of urolithiasis patients. Methodology: Glutathione peroxidase (GPx), catalase (CAT) and malondialadehyde (MDA) in serum of urolithiasis patients have been measured. Results: The study has revealed a significant increase in MDA and a significant decrease in GPx and CAT. There have been no significant correlations of serum MDA, GPx and CAT to the size and number of stones with no differences in their levels among patients with one stone, two stones and multiple stones. Anatomically the distributions of urinary stones have been 70.14% renal, 19.30% ureteric and 3.15% urinary bladder. There have been no significant difference in serum levels of neither MDA nor CAT among all the anatomical sites of the stone, while GPx has shown a significant difference in serum of patients with renal calyceal, renal pelvic, ureteric and vesical stones. Patients with recurrent episode of urinary stone have been 63.33%. Family histories of urolithiasis have been negative in 73.33% of the patients. Neither recurrence of urinary stone nor family history of urolithiasis have shown a significant correlation with serum levels of MDA, GPx and CAT. Conclusion: The role of lipid peroxidation and antioxidant enzymes is present in the pathogenesis of urinary stone, but their levels don't affect by the size, the number and the anatomical position of stones (apart of GPx which has been affected by the anatomical position of the stone) and the duration, recurrence, and family history of the disease. (author)

  19. Factors that affect leaf extracellular ascorbic acid content and redox status

    Energy Technology Data Exchange (ETDEWEB)

    Burkey, K.O.; Fiscus, E.L. [North Carolina State Univ., United States dept. og Agriculture-Agricultural Research Service and Dept. of Crop Science, Raleigh, NC (United States); Eason, G. [North Carolina, State Univ., United States Dept. of Plant Pathology, Raleigh, NC (United States)

    2003-01-01

    Leaf ascorbic acid content and redox status were compared in ozone-tolerant (Provider) and ozone-sensitive (S156) genotypes of snap bean (Phaseolus vulgaris L.). Plants were grown in pots for 24 days under charcoal-filtered air (CF) conditions in open-top field chambers and then maintained as CF controls (29 nmol mol{sup 1} ozone) or exposed to elevated ozone (71 nmol mol{sup 1} ozone). Following a 10-day treatment, mature leaves of the same age were harvested early in the morning (06:00-08:00 h) or in the afternoon (13:00-15:00 h) for analysis of ascorbic acid (AA) and dehydroascorbic acid (DHA). Vacuum infiltration methods were used to separate leaf AA into apoplast and symplast fractions. The total ascorbate content [AA + DHA] of leaf tissue averaged 28% higher in Provider relative to S156, and Provider exhibited a greater capacity to maintain [AA + DHA] content under ozone stress. Apoplast [AA + DHA] content was 2-fold higher in tolerant Provider (360 nmol g{sup 1} FW maximum) relative to sensitive S156 (160 nmol g1 FW maximum) regardless of sampling period or treatment, supporting the hypothesis that extracellular AA is a factor in ozone tolerance. Apoplast [AA + DHA] levels were significantly higher in the afternoon than early morning for both genotypes, evidence for short-term regulation of extracellular ascorbate content. Total leaf ascorbate was primarily reduced with AA/[AA + DHA] ratios of 0.81-0.90. In contrast, apoplast AA/[AA + DHA] ratios were 0.01-0.60 and depended on genotype and ozone treatment. Provider exhibited a greater capacity to maintain extracellular AA/[AA + DHA] ratios under ozone stress, suggesting that ozone tolerance is associated with apoplast ascorbate redox status. (au)

  20. 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.

  1. Role of glutathione metabolism status in the definition of some cellular parameters and oxidative stress tolerance of Saccharomyces cerevisiae cells growing as biofilms.

    Science.gov (United States)

    Gales, Grégoire; Penninckx, Michel; Block, Jean-Claude; Leroy, Pierre

    2008-08-01

    The resistance of Saccharomyces cerevisiae to oxidative stress (H(2)O(2) and Cd(2+)) was compared in biofilms and planktonic cells, with the help of yeast mutants deleted of genes related to glutathione metabolism and oxidative stress. Biofilm-forming cells were found predominantly in the G1 stage of the cell cycle. This might explain their higher tolerance to oxidative stress and the young replicative age of these cells in an old culture. The reduced glutathione status of S. cerevisiae was affected by the growth phase and apparently plays an important role in oxidative stress tolerance in cells growing as a biofilm.

  2. Fasting, but Not Aging, Dramatically Alters the Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Katja E. Menger

    2015-06-01

    Full Text Available Altering the redox state of cysteine residues on protein surfaces is an important response to environmental challenges. Although aging and fasting alter many redox processes, the role of cysteine residues is uncertain. To address this, we used a redox proteomic technique, oxidative isotope-coded affinity tags (OxICAT, to assess cysteine-residue redox changes in Drosophila melanogaster during aging and fasting. This approach enabled us to simultaneously identify and quantify the redox state of several hundred cysteine residues in vivo. Cysteine residues within young flies had a bimodal distribution with peaks at ∼10% and ∼85% reversibly oxidized. Surprisingly, these cysteine residues did not become more oxidized with age. In contrast, 24 hr of fasting dramatically oxidized cysteine residues that were reduced under fed conditions while also reducing cysteine residues that were initially oxidized. We conclude that fasting, but not aging, dramatically alters cysteine-residue redox status in D. melanogaster.

  3. In vivo evaluation of different alterations of redox status by studying pharmacokinetics of nitroxides using magnetic resonance techniques

    Science.gov (United States)

    Bačić, Goran; Pavićević, Aleksandra; Peyrot, Fabienne

    2015-01-01

    Free radicals, particularly reactive oxygen species (ROS), are involved in various pathologies, injuries related to radiation, ischemia-reperfusion or ageing. Unfortunately, it is virtually impossible to directly detect free radicals in vivo, but the redox status of the whole organism or particular organ can be studied in vivo by using magnetic resonance techniques (EPR and MRI) and paramagnetic stable free radicals – nitroxides. Here we review results obtained in vivo following the pharmacokinetics of nitroxides on experimental animals (and a few in humans) under various conditions. The focus was on conditions where the redox status has been altered by induced diseases or harmful agents, clearly demonstrating that various EPR/MRI/nitroxide combinations can reliably detect metabolically induced changes in the redox status of organs. These findings can improve our understanding of oxidative stress and provide a basis for studying the effectiveness of interventions aimed to modulate oxidative stress. Also, we anticipate that the in vivo EPR/MRI approach in studying the redox status can play a vital role in the clinical management of various pathologies in the years to come providing the development of adequate equipment and probes. PMID:26827126

  4. In vivo evaluation of different alterations of redox status by studying pharmacokinetics of nitroxides using magnetic resonance techniques

    Directory of Open Access Journals (Sweden)

    Goran Bačić

    2016-08-01

    Full Text Available Free radicals, particularly reactive oxygen species (ROS, are involved in various pathologies, injuries related to radiation, ischemia-reperfusion or ageing. Unfortunately, it is virtually impossible to directly detect free radicals in vivo, but the redox status of the whole organism or particular organ can be studied in vivo by using magnetic resonance techniques (EPR and MRI and paramagnetic stable free radicals – nitroxides. Here we review results obtained in vivo following the pharmacokinetics of nitroxides on experimental animals (and a few in humans under various conditions. The focus was on conditions where the redox status has been altered by induced diseases or harmful agents, clearly demonstrating that various EPR/MRI/nitroxide combinations can reliably detect metabolically induced changes in the redox status of organs. These findings can improve our understanding of oxidative stress and provide a basis for studying the effectiveness of interventions aimed to modulate oxidative stress. Also, we anticipate that the in vivo EPR/MRI approach in studying the redox status can play a vital role in the clinical management of various pathologies in the years to come providing the development of adequate equipment and probes.

  5. The changes in redox status of ascorbate in stem tissue cells during Scots pine tree growth

    Directory of Open Access Journals (Sweden)

    G. F. Antonova

    2017-02-01

    Full Text Available The contents of ascorbate (AsA and dehydroascorbate (DHA and their ratio, showing cellular redox state of AsA, were studied in the cells of the separate tissues at different levels of Pinus sylvestris L. stem during early- and latewood formation. Morphological status of the cells in the tissues and the content of soluble carbohydrates were also estimated. The cellular redox potential of AsA has been found to depend on the type of tissue, cell development degree, the level of stem and the type of forming wood. The content of AsA and AsA/DHA ratio in the cells of non-conducting phloem along the stem were higher than in mature xylem and less during earlywood than latewood formation. The cells of conducting phloem and forming xylem, as the principal tissues taking part in annual ring wood formation, differed in the content of acids in the course of early and late xylem formation. Along the stem, the content of AsA decreased in conducting phloem cells and increased in the cells of forming xylem during both early- and latewood formation. The AsA/DHA of conducting phloem during earlywood formation was greatest below the stem and diminished to the top of the tree, while in the course of latewood development it was similar at all levels. In forming xylem AsA/DHA increased to the top of tree during the early xylem formation and decreased in late xylem that indicates the differences in oxidation-reduction reactions into the cells of two type of forming wood. The data are discussed according to morphological development of cells and the content of carbohydrates.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

  8. Oxidative status, in vitro iron-induced lipid oxidation and superoxide dismutase, catalase and glutathione peroxidase activities in rhea meat.

    Science.gov (United States)

    Terevinto, A; Ramos, A; Castroman, G; Cabrera, M C; Saadoun, A

    2010-04-01

    Rhea (Rhea americana) muscles Obturatorius medialis (OM) Iliotibialis lateralis (IL) and Iliofibularis (I), obtained from farmed animals, were evaluated regarding their oxidative/antioxidant status. The mean level of thiobarbituric acid reactive substances (TBARS) expressed as malonaldehyde (MDA) content was of 0.84 mg MDA/kg wet tissue for the three muscles. TBARS level was significantly higher in IL than OM and I, with the two latter showing similar levels. The mean level of carbonyl proteins expressed as dinitrophenylhydrazine (DNPH) was 1.59 nmol DNPH mg(-1). Carbonyl protein levels were significantly different (POM>I). Iron-induced TBARS generation was not significantly different between the three muscles at any time, nor for each muscle during the 5 h of the experiment. Superoxide dismutase activity in IL muscle was significantly higher (P<0.05) than in I muscle. However, the difference between IL and OM muscles was not significant. The differences between the three muscles became not significant when the results were expressed by mg of protein contained in the extract, instead by g of wet tissue. No differences were found for catalase (micromol of discomposed H(2)O(2) min(-1) g(-1) wet tissue or by mg of protein contained in the extract) and glutathione peroxidase (micromol ol of oxidized NADPH min(-1) g(-1) of wet tissue or by mg of protein contained in the extract) activities between the three muscles. 2009 Elsevier Ltd. All rights reserved.

  9. Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats

    Directory of Open Access Journals (Sweden)

    Anil Kumar Saxena

    2015-06-01

    Full Text Available Aging related reduction in cerebral blood flow (CBF has been linked with neurodegenerative disorders including Alzheimer's disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO in rats. Since oxidative stress, leading to neuronal apoptosis and death, is one of the mechanisms, which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the ROS status by measuring the levels of anti-oxidant enzymes that might occur during chronic cerebral hypoperfusion. Antioxidant enzymes namely glutathione peroxidase (GPx, superoxide dismutase (SOD, and catalase were measured in the brain tissue at eight weeks of 2VO induction in rats. Results show significantly elevated levels of GPx, SOD, and catalase enzymes as compared with the control group. It is possible that compensatory rise in antioxidant enzymes occurs in response to increased oxidative stress following ischemic insult.

  10. N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice.

    Science.gov (United States)

    Amrouche-Mekkioui, Ilhem; Djerdjouri, Bahia

    2012-09-15

    The effect of N-acetylcysteine (NAC), a pharmacological antioxidant was investigated in a murine model of chronic colitis. Male NMRI mice were given 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 10 days of water, three times. Compared to control mice given water, DSS-treated mice displayed severe imbalanced redox status with decreased glutathione and catalase, but increased malondialdehyde, protein carbonyls, nitric oxide and myeloperoxidase levels, at days 35th (active colitis) and 45th (recovery period). It also resulted in mitochondrial dysfunction, mucosal ulcers, mucin-depleted crypts and epithelial cell apoptosis. Crypt abscesses and glandular hyperplasia occurred selectively in distal colon. NAC (150 mg/kg) given in drinking water for 45 days along with 3 DSS cycles improved the hallmarks of DSS-colitis. Interestingly, the moderate impact of NAC on lipids and proteins oxidation correlated with myeloperoxidase and nitric oxide levels.NAC as a mucoregulator and a thiol restoring agent is protective on oxidative crypt alterations, mucin depletion, epithelial cell hyperplasia and apoptosis. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived reactive oxygen species in mice DDS-colitis, suggesting that a long term NAC diet might be beneficial in inflammatory bowel diseases and colorectal cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. 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.

  12. Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy

    Directory of Open Access Journals (Sweden)

    Antonina Luca

    2016-01-01

    Full Text Available Objective. To discuss the link between glycogen synthase kinase-3 (GSK3 and the main biological alterations demonstrated in bipolar disorder (BD, with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

  13. Redox Status of β2GPI in Different Stages of Diabetic Angiopathy

    Directory of Open Access Journals (Sweden)

    Jun Ma

    2016-01-01

    Full Text Available We explored the redox status of beta 2 glycoprotein I (β2GPI in different stages of diabetic angiopathy. Type 2 diabetes mellitus (T2DM had a significantly lower proportion of reduced β2GPI as compared to healthy controls (p0.05. The mild-A-stenosis group and mild-diabetic retinopathy (DR groups had higher proportion of reduced β2GPI than their severely affected counterparts. The mild-slow nerve conduction velocity (NCVS group had higher proportion of reduced β2GPI than normal nerve conduction velocity (NCVN group and severe-NCVS groups. The proportion of reduced β2GPI was in positive correlation with 24 h urine microalbumin and total urine protein, and the proportion of reduced β2GPI was in negative correlation with serum and skin advanced glycation end products (AGEs. Taken together, our data implicate that the proportion of reduced β2GPI increased in the early stage of angiopathy and decreased with the aggravation of angiopathy.

  14. Interactive toxicity of inorganic mercury and trichloroethylene in rat and human proximal tubules: Effects on apoptosis, necrosis, and glutathione status

    International Nuclear Information System (INIS)

    Lash, Lawrence H.; Putt, David A.; Hueni, Sarah E.; Payton, Scott G.; Zwickl, Joshua

    2007-01-01

    Simultaneous or prior exposure to one chemical may alter the concurrent or subsequent response to another chemical, often in unexpected ways. This is particularly true when the two chemicals share common mechanisms of action. The present study uses the paradigm of prior exposure to study the interactive toxicity between inorganic mercury (Hg 2+ ) and trichloroethylene (TRI) or its metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in rat and human proximal tubule. Pretreatment of rats with a subtoxic dose of Hg 2+ increased expression of glutathione S-transferase-α1 (GSTα1) but decreased expression of GSTα2, increased activities of several GSH-dependent enzymes, and increased GSH conjugation of TRI. Primary cultures of rat proximal tubular (rPT) cells exhibited both necrosis and apoptosis after incubation with Hg 2+ . Pretreatment of human proximal tubular (hPT) cells with Hg 2+ caused little or no changes in GST expression or activities of GSH-dependent enzymes, decreased apoptosis induced by TRI or DCVC, but increased necrosis induced by DCVC. In contrast, pretreatment of hPT cells with TRI or DCVC protected from Hg 2+ by decreasing necrosis and increasing apoptosis. Thus, whereas pretreatment of hPT cells with Hg 2+ exacerbated cellular injury due to TRI or DCVC by shifting the response from apoptosis to necrosis, pretreatment of hPT cells with either TRI or DCVC protected from Hg 2+ -induced cytotoxicity by shifting the response from necrosis to apoptosis. These results demonstrate that by altering processes related to GSH status, susceptibilities of rPT and hPT cells to acute injury from Hg 2+ , TRI, or DCVC are markedly altered by prior exposures

  15. 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

  16. The antioxidant master glutathione and periodontal health

    Directory of Open Access Journals (Sweden)

    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.

  17. The impact of intermittent exercise in a hypoxic environment on redox status and cardiac troponin release in the serum of well-trained marathon runners.

    Science.gov (United States)

    Li, Feifei; Nie, Jinlei; Lu, Yifan; Tong, Tom Kwok Keung; Yi, Longyan; Yan, Huiping; Fu, Frank Hoo Kin; Ma, Shengxia

    2016-10-01

    To investigate the effects of hypoxic training on redox status and cardiac troponin (cTn) release after intermittent exercise. Nine well-trained male marathon runners (age, 21.7 ± 2.3 year; body mass, 64.7 ± 4.8 kg; height, 177.9 ± 3.8 cm; and VO2max, 64.3 ± 6.7 ml kg(-1) min(-1)) completed intermittent exercise under normoxic [trial N; fraction of inspiration oxygen (FIO2), 21.0 %] and hypoxic (trial H; FIO2, 14.4 %) conditions in random order. Each bout of intermittent exercise included hard run (16.2 ± 0.8 km h(-1)) at 90 % VO2max for 2 min followed by easy run (9.0 ± 0.4 km h(-1)) at 50 % VO2max for 2 min and 23 bouts in 92 min totally. Malondialdehyde, reduced glutathione (GSH), superoxide dismutase, an estimate of total antioxidant capacity (T-AOC), high-sensitivity cardiac troponin T (hs-cTnT), and cardiac troponin I (cTnI) were measured before, immediately after (0 h), and 2, 4, and 24 h after the completion of trials N and H. GSH was increased immediately after trial N. T-AOC was lower 4 h after trial H than trial N. Hs-cTnT was elevated from 0 to 4 h and returned to baseline 24 h after both trials. CTnI was increased after trial H; peaked at 2-4 h and returned to below the detection by 24 h. The overall redox status was balanced under normoxic conditions, and exercise-induced cTn release did not deviate. However, the protective effects of antioxidant were weaker in the hypoxic state than normoxic, and the stress on the myocardium induced by intermittent exercise was transiently aggravated.

  18. 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.

  19. Lamb survival, glutathione redox state and immune function of neonates and lambs from periparturient Merino ewes supplemented with rumen-protected methionine.

    Science.gov (United States)

    Liu, Shimin; Lei, Jason; Hancock, Serina; Scanlan, Victoria; Broomfield, Steve; Currie, Andrew; Thompson, Andrew

    2016-10-01

    Wool growth in Merino sheep demands a high level of sulphur amino acids, competing with body growth and the immune system, which may play a role in increasing the risk of lamb mortality. The hypothesis that dietary supplementation of methionine (Met) to Merino ewes during the late stages of pregnancy will improve foetal growth and alter immune competency of ewes and lambs was tested in a total of 120 grazing, pregnant Merino ewes. Sixty ewes were group-supplemented with 6.3 g/d rumen-protected Met (Met-Plus) per sheep from day 111 of pregnancy until day 7 after lambing, and the other 60 animals were used as a non-supplemented Control. Lambs from Met-supplemented ewes tended to be 10% heavier than Control lambs (p = 0.10), which did not affected the survival rate at weaning significantly. The supplemented ewes had slightly higher concentrations of total glutathione (GSH) in plasma at lambing (p ewes was elevated at lambing (p ewes were undergoing increased oxidative stress. The Met supplementation elevated the total IgG concentration (p < 0.05) in lambs aged 4 and 6 weeks, but did not change the IgG concentrations in colostrum and in plasma of 1-week-old lambs, and white blood cell counts and leukocyte types. The trend towards higher lamb birth weights in the Met-supplemented group requires further investigation as this may influence survival at birth and weaning.

  20. Severe exercise and exercise training exert opposite effects on human neutrophil apoptosis via altering the redox status.

    Directory of Open Access Journals (Sweden)

    Guan-Da Syu

    Full Text Available Neutrophil spontaneous apoptosis, a process crucial for immune regulation, is mainly controlled by alterations in reactive oxygen species (ROS and mitochondria integrity. Exercise has been proposed to be a physiological way to modulate immunity; while acute severe exercise (ASE usually impedes immunity, chronic moderate exercise (CME improves it. This study aimed to investigate whether and how ASE and CME oppositely regulate human neutrophil apoptosis. Thirteen sedentary young males underwent an initial ASE and were subsequently divided into exercise and control groups. The exercise group (n = 8 underwent 2 months of CME followed by 2 months of detraining. Additional ASE paradigms were performed at the end of each month. Neutrophils were isolated from blood specimens drawn at rest and immediately after each ASE for assaying neutrophil spontaneous apoptosis (annexin-V binding on the outer surface along with redox-related parameters and mitochondria-related parameters. Our results showed that i the initial ASE immediately increased the oxidative stress (cytosolic ROS and glutathione oxidation, and sequentially accelerated the reduction of mitochondrial membrane potential, the surface binding of annexin-V, and the generation of mitochondrial ROS; ii CME upregulated glutathione level, retarded spontaneous apoptosis and delayed mitochondria deterioration; iii most effects of CME were unchanged after detraining; and iv CME blocked ASE effects and this capability remained intact even after detraining. Furthermore, the ASE effects on neutrophil spontaneous apoptosis were mimicked by adding exogenous H(2O(2, but not by suppressing mitochondrial membrane potential. In conclusion, while ASE induced an oxidative state and resulted in acceleration of human neutrophil apoptosis, CME delayed neutrophil apoptosis by maintaining a reduced state for long periods of time even after detraining.

  1. An evaluation of heat on protein oxidation of soy protein isolate or soy protein isolate mixed with soybean oil and its consequences on redox status of broilers at early age

    Directory of Open Access Journals (Sweden)

    Xianglun Zhang

    2017-08-01

    Full Text Available Objective The objective of this study was to evaluate effects of heat treatment and soybean oil inclusion on protein oxidation of soy protein isolate (SPI and of oxidized protein on redox status of broilers at an early age. Methods SPI mixed with soybean oil (SPIO heated at 100°C for 8 h was used to evaluate protein oxidation of SPI. A total of two hundred and sixteen 1-day-old Arbor Acres chicks were divided into 3 groups with 6 replicates of 12 birds, receiving basal diet (CON, heat-oxidized SPI diet (HSPI or mixture of SPI and 2% soybean oil diet (HSPIO for 21 d, respectively. Results Increased protein carbonyl, decreased protein sulfhydryl of SPI were observed as heating time increased in all treatments (p<0.05. Addition of 2% soybean oil increased protein carbonyl of SPI at 8 h heating (p<0.05. Dietary HSPI and HSPIO decreased the average daily gain of broilers as compared with the CON (p<0.05. Broilers fed HSPI and HSPIO exhibited decreased glutathione (GSH in serum, catalase activity and total sulfhydryl in liver and increased malondialdehyde (MDA and protein carbonyl in serum, advanced oxidation protein products (AOPPs in liver and protein carbonyl in jejunal mucosa as compared with that of the CON (p<0.05. Additionally, broilers receiving HSPIO showed decreased glutathione peroxidase activity (GSH-Px in serum, GSH and hydroxyl radical scavenging capacity in liver, GSH-Px activity in duodenal mucosa, GSH-Px activity and superoxide anion radical scavenging capacity in jejunal mucosa and increased AOPPs in serum, MDA and protein carbonyl in liver, MDA and AOPPs in jejunal mucosa (p<0.05. Conclusion Protein oxidation of SPI can be induced by heat and soybean oil and oxidized protein resulted in redox imbalance in broilers at an early age.

  2. Materials and Systems for Organic Redox Flow Batteries: Status and Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Xiaoliang [Joint Center for Energy Storage Research (JCESR), Argonne, Illinois 60439, United States; Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Pan, Wenxiao [Department; Duan, Wentao [Joint Center for Energy Storage Research (JCESR), Argonne, Illinois 60439, United States; Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Hollas, Aaron [Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Yang, Zheng [Joint Center for Energy Storage Research (JCESR), Argonne, Illinois 60439, United States; Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Li, Bin [Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Nie, Zimin [Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Liu, Jun [Joint Center for Energy Storage Research (JCESR), Argonne, Illinois 60439, United States; Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Reed, David [Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Wang, Wei [Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States; Sprenkle, Vincent [Energy & amp, Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, Washington 99354, United States

    2017-08-14

    Redox flow batteries are propitious stationary energy storage technologies with exceptional scalability and flexibility to improve the stability, efficiency and sustainability of our power grid. The redox-active materials are the central component to RFBs for achieving high energy density and good cyclability. Traditional inorganic-based materials encounter critical technical and economic limitations such as low solubility, inferior electrochemical activity, and high cost. Redox-active organic materials (ROMs) are promising alternative “green” candidates to push the boundaries of energy storage because of the significant advantages of molecular diversity, structural tailorability, and natural abundance. Here the recent development of a variety of ROM families and associated battery designs in both aqueous and nonaqueous electrolytes are reviewed. Moreover, the critical challenges and potential research opportunities for developing practically relevant organic flow batteries are discussed.

  3. Ovotoxicants 4-vinylcyclohexene 1,2-monoepoxide and 4-vinylcyclohexene diepoxide disrupt redox status and modify different electrophile sensitive target enzymes and genes in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Amos O. Abolaji

    2015-08-01

    Full Text Available The compounds 4-vinylcyclohexene 1,2-monoepoxide (VCM and 4-Vinylcyclohexene diepoxide (VCD are the two downstream metabolites of 4-vinylcyclohexene (VCH, an ovotoxic agent in mammals. In addition, VCM and VCD may be found as by-products of VCH oxidation in the environment. Recently, we reported the involvement of oxidative stress in the toxicity of VCH in Drosophila melanogaster. However, it was not possible to determine the individual contributions of VCM and VCD in VCH toxicity. Hence, we investigated the toxicity of VCM and VCD (10–1000 µM in flies after 5 days of exposure via the diet. Our results indicated impairments in climbing behaviour and disruptions in antioxidant balance and redox status evidenced by an increase in DCFH oxidation, decreases in total thiol content and glutathione-S-transferase (GST activity in the flies exposed to VCM and VCD (p<0.05. These effects were accompanied by disruptions in the transcription of the genes encoding the proteins superoxide dismutase (SOD1, kelch-like erythroid-derived cap-n-collar (CNC homology (ECH-associated protein 1 (Keap-1, mitogen activated protein kinase 2 (MAPK-2, catalase, Cyp18a1, JAFRAC 1 (thioredoxin peroxidase 1 and thioredoxin reductase 1 (TrxR-1 (p<0.05. VCM and VCD inhibited acetylcholinesterase (AChE and delta aminolevulinic acid dehydratase (δ-ALA D activities in the flies (p<0.05. Indeed, here, we demonstrated that different target enzymes and genes were modified by the electrophiles VCM and VCD in the flies. Thus, D. melanogaster has provided further lessons on the toxicity of VCM and VCD which suggest that the reported toxicity of VCH may be mediated by its transformation to VCM and VCD.

  4. Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space

    DEFF Research Database (Denmark)

    Indo, Hiroko P; Majima, Hideyuki J; Terada, Masahiro

    2016-01-01

    reductions in the mtRNA/nRNA ratios in both the Inflight and Postflight samples. The mtRNA/mtDNA ratios were relatively constant, except in the Postflight samples. Using the same samples, the expression of redox and signal transduction related genes, MnSOD, CuZnSOD, Nrf2, Keap1, GPx4 and Catalase was also...... examined. The results of the combined data from Preflight, Inflight and Postflight show a significant decrease in the expression of all of the redox-related genes in the samples collected Postflight, with the exception of Catalase, which show no change. This decreased expression may contribute to increased...

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

    Directory of Open Access Journals (Sweden)

    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. 

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

    Directory of Open Access Journals (Sweden)

    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

  7. Effect of Multicomponent Training on Blood Pressure, Nitric Oxide, Redox Status, and Physical Fitness in Older Adult Women: Influence of Endothelial Nitric Oxide Synthase (NOS3 Haplotypes

    Directory of Open Access Journals (Sweden)

    Atila Alexandre Trapé

    2017-01-01

    Full Text Available The purpose of this study was to verify the influence of the genotype or haplotype (interaction of the NOS3 polymorphisms [-786T>C, 894G>T (Glu298Asp, and intron 4b/a] on the response to multicomponent training (various capacities and motor skills on blood pressure (BP, nitrite concentration, redox status, and physical fitness in older adult women. The sample consisted of 52 participants, who underwent body mass index and BP assessments. Physical fitness was evaluated by six-minute walk, elbow flexion, and sit and stand up tests. Plasma/blood samples were used to evaluate redox status, nitrite concentration, and genotyping. Associations were observed between isolated polymorphisms and the response of decreased systolic and diastolic BP and increased nitrite concentration and antioxidant activity. In the haplotype analysis, the group composed of ancestral alleles (H1 was the only one to present improvement in all variables studied (decrease in systolic and diastolic BP, improvement in nitrite concentration, redox status, and physical fitness, while the group composed of variant alleles (H8 only demonstrated improvement in some variables of redox status and physical fitness. These findings suggest that NOS3 polymorphisms and physical training are important interacting variables to consider in evaluating redox status, nitric oxide availability and production, and BP control.

  8. Eclipta yellow vein virus enhances chlorophyll destruction, singlet oxygen production and alters endogenous redox status in Andrographis paniculata.

    Science.gov (United States)

    Khan, Asifa; Luqman, Suaib; Masood, Nusrat; Singh, Dhananjay Kumar; Saeed, Sana Tabanda; Samad, Abdul

    2016-07-01

    The infection of Eclipta yellow vein virus [EcYVV-IN, Accession No. KC476655], recently reported for the first time, on Andrographis paniculata was studied for redox-mediated alteration mechanism in infected plants. A. paniculata, an important medicinal plant, is used in traditional Indian, Chinese and modern system of medicine. Andrographolide, one of the foremost components of this plant, is known for its varied pharmacological properties. Our investigation provides insight into the effect of virus-induced changes in the singlet oxygen quenching due to the alteration in pigment content (chlorophyll and carotenoids) as well as activation of plant secondary metabolism along with defense activation leading to changes in enzymatic and non-enzymatic redox status. Due to infection, a reduction in carotenoid content was observed which leads to reduced quenching of singlet oxygen. An increased level of enzymatic (SOD and APX) and non-enzymatic antioxidant (DPPH, FRAP, RP, NO, TAC and TP) activities were also observed in virus-infected plants with a positive correlation (>0.9). However, CAT activity was diminished which could be either due to its proteolytic degradation or inactivation by superoxide anions (O(2-.)), NO or peroxynitrite radicals. A significant (p < 0.05) increase in total phenolic content was observed in the infected plants while no considerable difference was seen in the total flavonoid content. Our results highlighted the alteration in redox status caused by virus-induced biotic stress on the plants and could be useful for understanding the after effects of viral infection This study could also be helpful in developing biomimetic methods for improving the production of secondary metabolites of pharmaceutical importance. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. 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

  10. Redox signaling in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    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.

  11. Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH.

    Science.gov (United States)

    Bruce, Kimberley D; Szczepankiewicz, Dawid; Sihota, Kiran K; Ravindraanandan, Manoj; Thomas, Hugh; Lillycrop, Karen A; Burdge, Graham C; Hanson, Mark A; Byrne, Christopher D; Cagampang, Felino R

    2016-07-01

    We have previously shown that high fat (HF) feeding during pregnancy primes the development of non-alcoholic steatohepatits (NASH) in the adult offspring. However, the underlying mechanisms are unclear. Since the endogenous molecular clock can regulate hepatic lipid metabolism, we investigated whether exposure to a HF diet during development could alter hepatic clock gene expression and contribute to NASH onset in later life. Female mice were fed either a control (C, 7%kcal fat) or HF (45%kcal fat) diet. Offspring were fed either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid metabolism (Rev-Erbα, Rev-Erbβ, RORα, and Srebp1c) were measured in offspring livers. Offspring fed a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet developed NASH, coupled with significantly reduced NAD(+)/NADH (pNASH in adulthood, involving altered cellular redox status, reduced sirtuin abundance, and desynchronized clock gene expression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Redox Mediators for Li-O2 Batteries: Status and Perspectives.

    Science.gov (United States)

    Park, Jin-Bum; Lee, Seon Hwa; Jung, Hun-Gi; Aurbach, Doron; Sun, Yang-Kook

    2018-01-01

    Li-O 2 batteries have received much attention due to their extremely large theoretical energy density. However, the high overpotentials required for charging Li-O 2 batteries lower their energy efficiency and degrade the electrolytes and carbon electrodes. This problem is one of the main obstacles in developing practical Li-O 2 batteries. To solve this problem, it is important to facilitate the oxidation of Li 2 O 2 upon charging by using effective electrocatalysis. Using solid catalysts is not too effective for oxidizing the electronically isolating Li-peroxide layers. In turn, for soluble catalysts, red-ox mediators (RMs) are homogeneously dissolved in the electrolyte solutions and can effectively oxidize all of the Li 2 O 2 precipitated during discharge. RMs can decompose solid Li 2 O 2 species no matter their size, morphology, or thickness and thus dramatically increase energy efficiency. However, some negative side effects, such as the shuttle reactions of RMs and deterioration of the Li-metal occur. Therefore, it is necessary to study the activity and stability of RMs in Li-O 2 batteries in detail. Herein, recent studies related to redox mediators are reviewed and the mechanisms of redox reactions are illustrated. The development opportunities of RMs for this important battery technology are discussed and future directions are suggested. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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....

  14. Blood Haematology, Serum Thyroid Hormones and Glutathione Peroxidase Status in Kacang Goats Fed Inorganic Iodine and Selenium Supplemented Diets

    Directory of Open Access Journals (Sweden)

    Z. A. Aghwan

    2013-11-01

    Full Text Available The effects of dietary supplementation of selenium (Se, iodine (I, and a combination of both on the blood haematology, serum free thyroxine (FT4 and free triiodothyronine (FT3 hormones and glutathione peroxidase enzyme (GSH-Px activity were examined on twenty four (7 to 8 months old, 22±1.17 kg live weight Kacang crossbred male goats. Animals were randomly assigned to four dietary treatments (6 animals in each group. Throughout 100 d of feeding trial, the animals of control group (CON received a basal diet, while the other three groups were offered basal diet supplemented with 0.6 mg/kg diet DM Se (SS, or 0.6 mg/kg diet DM I (PI, or a combination of both Se and I, each at 0.6 mg/kg diet DM (SSPI. The haematological attributes which are haemoglobin (Hb, red blood cell (RBC, packed cell volume (PCV, mean cell volume (MCV, white blood cells (WBC, band neutrophils (B Neut, segmented neutrophils (S Neut, lymphocytes (Lymph, monocytes (Mono, eosinophils (Eosin and basophils (Baso were similar among the four treatment groups, while serum levels of Se and I increased significantly (p<0.05 in the supplemented groups. The combined dietary supplementation of Se and I (SSPI significantly increased serum FT3 in the supplemented animals. Serum GSH-Px activity increased significantly in the animals of SS and SSPI groups. It is concluded that the dietary supplementation of inorganic Se and I at a level of 0.6 mg/kg DM increased serum Se and I concentration, FT3 hormone and GSH-Px activity of Kacang crossbred male goats.

  15. 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

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

    Science.gov (United States)

    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

  17. Quantifying the global cellular thiol-disulfide status

    DEFF Research Database (Denmark)

    Hansen, Rosa E; Roth, Doris; Winther, Jakob R

    2009-01-01

    It is widely accepted that the redox status of protein thiols is of central importance to protein structure and folding and that glutathione is an important low-molecular-mass redox regulator. However, the total cellular pools of thiols and disulfides and their relative abundance have never been...... determined. In this study, we have assembled a global picture of the cellular thiol-disulfide status in cultured mammalian cells. We have quantified the absolute levels of protein thiols, protein disulfides, and glutathionylated protein (PSSG) in all cellular protein, including membrane proteins. These data...... cell types. However, when cells are exposed to a sublethal dose of the thiol-specific oxidant diamide, PSSG levels increase to >15% of all protein cysteine. Glutathione is typically characterized as the "cellular redox buffer"; nevertheless, our data show that protein thiols represent a larger active...

  18. Brevetoxin (PbTx-2) influences the redox status and NPQ of Karenia brevis by way of thioredoxin reductase.

    Science.gov (United States)

    Chen, Wei; Colon, Ricardo; Louda, J William; Del Rey, Freddy Rodriguez; Durham, Michaella; Rein, Kathleen S

    2018-01-01

    The Florida red tide dinoflagellate, Karenia brevis, is the major harmful algal bloom dinoflagellate of the Gulf of Mexico and plays a destructive role in the region. Blooms of K. brevis can produce brevetoxins: ladder-shaped polyether (LSP) compounds, which can lead to adverse human health effects, such as reduced respiratory function through inhalation exposure, or neurotoxic shellfish poisoning through consumption of contaminated shellfish. The endogenous role of the brevetoxins remains uncertain. Recent work has shown that some forms of NADPH dependent thioredoxin reductase (NTR) are inhibited by brevetoxin-2 (PbTx-2). The study presented herein reveals that high toxin and low toxin K. brevis, which have a ten-fold difference in toxin content, also show a significant difference in their ability, not only to produce brevetoxin, but also in their cellular redox status and distribution of xanthophyll cycle pigments. These differences are likely due to the inhibition of NTR by brevetoxin. The work could shed light on the physiological role that brevetoxin fills for K. brevis. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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

  20. Glutathione and Mitochondria

    Directory of Open Access Journals (Sweden)

    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.

  1. In vivo EPR pharmacokinetic evaluation of the redox status and the blood brain barrier permeability in the SOD1G93A ALS rat model.

    Science.gov (United States)

    Stamenković, Stefan; Pavićević, Aleksandra; Mojović, Miloš; Popović-Bijelić, Ana; Selaković, Vesna; Andjus, Pavle; Bačić, Goran

    2017-07-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1 G93A ALS rat model in the presymptomatic (preALS) and symptomatic (ALS) stages of the disease were investigated by in vivo EPR spectroscopy using three aminoxyl radicals with different cell membrane and BBB permeabilities, Tempol, 3-carbamoyl proxyl (3CP), and 3-carboxy proxyl (3CxP). Additionally, the redox status of the two brain regions previously implicated in disease pathology, brainstem and hippocampus, was investigated by spectrophotometric biochemical assays. The EPR results indicated that among the three spin probes, 3CP is the most suitable for reporting the intracellular redox status changes, as Tempol was reduced in vivo within minutes (t 1/2 =2.0±0.5min), thus preventing reliable kinetic modeling, whereas 3CxP reduction kinetics gave divergent conclusions, most probably due to its membrane impermeability. It was observed that the reduction kinetics of 3CP in vivo, in the head of preALS and ALS SOD1 G93A rats was altered compared to the controls. Pharmacokinetic modeling of 3CP reduction in vivo, revealed elevated tissue distribution and tissue reduction rate constants indicating an altered brain tissue redox status, and possibly BBB disruption in these animals. The preALS and ALS brain tissue homogenates also showed increased nitrilation, superoxide production, lipid peroxidation and manganese superoxide dismutase activity, and a decreased copper-zinc superoxide dismutase activity. The present study highlights in vivo EPR spectroscopy as a reliable tool for the investigation of

  2. Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions

    Science.gov (United States)

    Marullo, Rossella; Werner, Erica; Degtyareva, Natalya; Moore, Bryn; Altavilla, Giuseppe; Ramalingam, Suresh S.; Doetsch, Paul W.

    2013-01-01

    Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy. PMID:24260552

  3. Phosphatidylcholine formation by LPCAT1 is regulated by Ca2+ and the redox status of the cell

    Directory of Open Access Journals (Sweden)

    Soupene Eric

    2012-06-01

    Full Text Available Abstract Background Unsaturated fatty acids are susceptible to oxidation and damaged chains are removed from glycerophospholipids by phospholipase A2. De-acylated lipids are then re-acylated by lysophospholipid acyltransferase enzymes such as LPCAT1 which catalyses the formation of phosphatidylcholine (PC from lysoPC and long-chain acyl-CoA. Results Activity of LPCAT1 is inhibited by Ca2+, and a Ca2+-binding motif of the EF-hand type, EFh-1, was identified in the carboxyl-terminal domain of the protein. The residues Asp-392 and Glu-403 define the loop of the hairpin structure formed by EFh-1. Substitution of D392 and E403 to alanine rendered an enzyme insensitive to Ca2+, which established that Ca2+ binding to that region negatively regulates the activity of the acyltransferase amino-terminal domain. Residue Cys-211 of the conserved motif III is not essential for catalysis and not sufficient for sensitivity to treatment by sulfhydryl-modifier agents. Among the several active cysteine-substitution mutants of LPCAT1 generated, we identified one to be resistant to treatment by sulfhydryl-alkylating and sulfhydryl-oxidizer agents. Conclusion Mutant forms of LPCAT1 that are not inhibited by Ca2+ and sulfhydryl-alkylating and –oxidizing agents will provide a better understanding of the physiological function of a mechanism that places the formation of PC, and the disposal of the bioactive species lysoPC, under the control of the redox status and Ca2+ concentration of the cell.

  4. Benzene Uptake and Glutathione S-transferase T1 Status as Determinants of S-Phenylmercapturic Acid in Cigarette Smokers in the Multiethnic Cohort.

    Directory of Open Access Journals (Sweden)

    Christopher A Haiman

    Full Text Available Research from the Multiethnic Cohort (MEC demonstrated that, for the same quantity of cigarette smoking, African Americans and Native Hawaiians have a higher lung cancer risk than Whites, while Latinos and Japanese Americans are less susceptible. We collected urine samples from 2,239 cigarette smokers from five different ethnic groups in the MEC and analyzed each sample for S-phenylmercapturic acid (SPMA, a specific biomarker of benzene uptake. African Americans had significantly higher (geometric mean [SE] 3.69 [0.2], p<0.005 SPMA/ml urine than Whites (2.67 [0.13] while Japanese Americans had significantly lower levels than Whites (1.65 [0.07], p<0.005. SPMA levels in Native Hawaiians and Latinos were not significantly different from those of Whites. We also conducted a genome-wide association study in search of genetic risk factors related to benzene exposure. The glutathione S-transferase T1 (GSTT1 deletion explained between 14.2-31.6% (p = 5.4x10-157 and the GSTM1 deletion explained between 0.2%-2.4% of the variance (p = 1.1x10-9 of SPMA levels in these populations. Ethnic differences in levels of SPMA remained strong even after controlling for the effects of these two deletions. These results demonstrate the powerful effect of GSTT1 status on SPMA levels in urine and show that uptake of benzene in African American, White, and Japanese American cigarette smokers is consistent with their lung cancer risk in the MEC. While benzene is not generally considered a cause of lung cancer, its metabolite SPMA could be a biomarker for other volatile lung carcinogens in cigarette smoke.

  5. N-Acetyl Cysteine Protects against Methamphetamine-Induced Dopaminergic Neurodegeneration via Modulation of Redox Status and Autophagy in Dopaminergic Cells

    Directory of Open Access Journals (Sweden)

    Prashanth Chandramani Shivalingappa

    2012-01-01

    Full Text Available Methamphetamine- (MA- induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. Our previous study demonstrated that MA induces autophagy in a dopaminergic neuronal cell model (N27 cells. The cellular mechanisms underlying MA-induced autophagy and apoptosis remain poorly characterized. In the present study we sought to investigate the importance of GSH redox status in MA-induced neurotoxicity using a thiol antioxidant, N-acetylcysteine (NAC. Morphological and biochemical analysis revealed that MA-induced autophagy in N27 dopaminergic cells was associated with pronounced depletion of GSH levels. Moreover, pretreatment with NAC reduced MA-induced GSH depletion and autophagy, while depletion of GSH using L-buthionine sulfoximine (L-BSO enhanced autophagy. Furthermore, treatment with NAC significantly attenuated MA-induced apoptotic cell death as well as oxidative stress markers, namely, 3-nitrotyrosine (3-NT and 4-hydroxynonenal (4-HNE. Together, these results suggest that NAC exhibits significant protective effects against MA-induced dopaminergic cell death, presumably via modulation of the GSH level and autophagy. Collectively, our data provide mechanistic insights into the role of cellular GSH redox status in MA-induced autophagy and apoptotic cell death, and additional studies are needed to determine the therapeutic effectiveness of cellular redox modifiers in attenuating dopaminergic neurodegeneration in vivo.

  6. 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...

  7. OXIDATIVE MODIFICATION OF PROTEINS AND GLUTATHIONE SYSTEM IN ADIPOCYTES UNDER DIABETES

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Experimental Evidence that In Vivo Intracerebral Administration of L-2-Hydroxyglutaric Acid to Neonatal Rats Provokes Disruption of Redox Status and Histopathological Abnormalities in the Brain.

    Science.gov (United States)

    Ribeiro, Rafael Teixeira; Zanatta, Ângela; Amaral, Alexandre Umpierrez; Leipnitz, Guilhian; de Oliveira, Francine Hehn; Seminotti, Bianca; Wajner, Moacir

    2018-04-01

    Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2-HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in the cerebral cortex and striatum of neonatal rats. L-2-HG markedly induced the generation of reactive oxygen species (increase of 2',7'-dichloroflurescein-DCFH-oxidation), lipid peroxidation (increase of malondialdehyde concentrations), and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione-GSH) and sulfhydryl content in the cerebral cortex. Alterations of the activities of various antioxidant enzymes were also observed in the cerebral cortex and striatum following L-2-HG administration. Furthermore, L-2-HG-induced lipid peroxidation and GSH decrease in the cerebral cortex were prevented by the antioxidant melatonin and by the classical antagonist of NMDA glutamate receptor MK-801, suggesting the involvement of reactive species and of overstimulation of NMDA receptor in these effects. Finally, L-2-HG provoked significant vacuolation and edema particularly in the cerebral cortex with less intense alterations in the striatum that were possibly associated with the unbalanced redox homeostasis caused by this metabolite. Taken together, it is presumed that these pathomechanisms may underlie the neurological symptoms and brain abnormalities observed in the affected patients.

  10. Compartment specific importance of glutathione during abiotic and biotic stress

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. 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

  13. The benefit of a supplement with the antioxidant melatonin on redox status and muscle damage in resistance-trained athletes.

    Science.gov (United States)

    Leonardo-Mendonça, Roberto C; Ocaña-Wilhelmi, Javier; de Haro, Tomás; de Teresa-Galván, Carlos; Guerra-Hernández, Eduardo; Rusanova, Iryna; Fernández-Ortiz, Marisol; Sayed, Ramy K A; Escames, Germaine; Acuña-Castroviejo, Darío

    2017-07-01

    Previous data showed that the administration of high doses of melatonin improved the circadian system in athletes. Here, we investigated in the same experimental paradigm whether the antioxidant properties of melatonin has also beneficial effects against exercise-induced oxidative stress and muscle damage in athletes. Twenty-four athletes were treated with 100 mg·day -1 of melatonin or placebo 30 min before bedtime during 4 weeks in a randomized double-blind scheme. Exercise intensity was higher during the study that before starting it. Blood samples were collected before and after treatment, and plasma was used for oxygen radical absorption capacity (ORAC), lipid peroxidation (LPO), nitrite plus nitrate (NOx), and advanced oxidation protein products (AOPP) determinations. Glutathione (GSH), glutathione disulphide (GSSG) levels, and glutathione peroxidase (GPx) and reductase (GRd) activities, were measured in erythrocytes. Melatonin intake increased ORAC, reduced LPO and NOx levels, and prevented the increase of AOPP, compared to placebo group. Melatonin was also more efficient than placebo in reducing GSSG·GSH -1 and GPx·GRd -1 ratios. Melatonin, but not placebo, reduced creatine kinase, lactate dehydrogenase, creatinine, and total cholesterol levels. Overall, the data reflect a beneficial effect of melatonin treatment in resistance-training athletes, preventing extra- and intracellular oxidative stress induced by exercise, and yielding further skeletal muscle protection against exercise-induced oxidative damage.

  14. Redox imbalance and mitochondrial abnormalities in the diabetic lung.

    Science.gov (United States)

    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.

  15. Oligo-Carrageenan Kappa-Induced Reducing Redox Status and Increase in TRR/TRX Activities Promote Activation and Reprogramming of Terpenoid Metabolism in Eucalyptus Trees

    Directory of Open Access Journals (Sweden)

    Alberto González

    2014-06-01

    Full Text Available In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR/thioredoxin(TRX system induced by oligo-carrageenan (OC kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(PH, ascorbate (ASC and (GSH synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%, α-pinene (7.4%, aromadendrene (3.6%, silvestrene (2.8%, sabinene (2% and α-terpineol (0.9%. Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65% and sabinene (0.8% and an increase in aromadendrene (5%, silvestrene (7.8% and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

  16. Oligo-carrageenan kappa-induced reducing redox status and increase in TRR/TRX activities promote activation and reprogramming of terpenoid metabolism in Eucalyptus trees.

    Science.gov (United States)

    González, Alberto; Gutiérrez-Cutiño, Marlen; Moenne, Alejandra

    2014-06-05

    In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR)/thioredoxin(TRX) system induced by oligo-carrageenan (OC) kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(P)H, ascorbate (ASC) and (GSH) synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO) and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%), α-pinene (7.4%), aromadendrene (3.6%), silvestrene (2.8%), sabinene (2%) and α-terpineol (0.9%). Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65%) and sabinene (0.8%) and an increase in aromadendrene (5%), silvestrene (7.8%) and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

  17. Modulation of Erythrocyte Plasma Membrane Redox System Activity by Curcumin

    Directory of Open Access Journals (Sweden)

    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.

  18. 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...

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

  3. Basal Glutathionylation of Na,K-ATPase α-Subunit Depends on Redox Status of Cells during the Enzyme Biosynthesis

    Directory of Open Access Journals (Sweden)

    Vladimir A. Mitkevich

    2016-01-01

    Full Text Available Many viruses induce oxidative stress and cause S-glutathionylation of Cys residues of the host and viral proteins. Changes in cell functioning during viral infection may be associated with glutathionylation of a number of key proteins including Na,K-ATPase which creates a gradient of sodium and potassium ions. It was found that Na,K-ATPase α-subunit has a basal glutathionylation which is not abrogated by reducing agent. We have shown that acute hypoxia leads to increase of total glutathionylation level of Na,K-ATPase α-subunit; however, basal glutathionylation of α-subunit increases under prolonged hypoxia only. The role of basal glutathionylation in Na,K-ATPase function remains unclear. Understanding significance of basal glutathionylation is complicated by the fact that there are no X-ray structures of Na,K-ATPase with the identified glutathione molecules. We have analyzed all X-ray structures of the Na,K-ATPase α-subunit from pig kidney and found that there are a number of isolated cavities with unresolved electron density close to the relevant cysteine residues. Analysis of the structures showed that this unresolved density in the structure can be occupied by glutathione associated with cysteine residues. Here, we discuss the role of basal glutathionylation of Na,K-ATPase α-subunit and provide evidence supporting the view that this modification is cotranslational.

  4. Basal Glutathionylation of Na,K-ATPase α-Subunit Depends on Redox Status of Cells during the Enzyme Biosynthesis.

    Science.gov (United States)

    Mitkevich, Vladimir A; Petrushanko, Irina Yu; Poluektov, Yuri M; Burnysheva, Ksenia M; Lakunina, Valentina A; Anashkina, Anastasia A; Makarov, Alexander A

    2016-01-01

    Many viruses induce oxidative stress and cause S-glutathionylation of Cys residues of the host and viral proteins. Changes in cell functioning during viral infection may be associated with glutathionylation of a number of key proteins including Na,K-ATPase which creates a gradient of sodium and potassium ions. It was found that Na,K-ATPase α-subunit has a basal glutathionylation which is not abrogated by reducing agent. We have shown that acute hypoxia leads to increase of total glutathionylation level of Na,K-ATPase α-subunit; however, basal glutathionylation of α-subunit increases under prolonged hypoxia only. The role of basal glutathionylation in Na,K-ATPase function remains unclear. Understanding significance of basal glutathionylation is complicated by the fact that there are no X-ray structures of Na,K-ATPase with the identified glutathione molecules. We have analyzed all X-ray structures of the Na,K-ATPase α-subunit from pig kidney and found that there are a number of isolated cavities with unresolved electron density close to the relevant cysteine residues. Analysis of the structures showed that this unresolved density in the structure can be occupied by glutathione associated with cysteine residues. Here, we discuss the role of basal glutathionylation of Na,K-ATPase α-subunit and provide evidence supporting the view that this modification is cotranslational.

  5. 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.

  6. Chloroplast Redox Status Modulates Genome-Wide Plant Responses during the Non-host Interaction of Tobacco with the Hemibiotrophic Bacterium Xanthomonas campestris pv. vesicatoria

    Directory of Open Access Journals (Sweden)

    Juan J. Pierella Karlusich

    2017-07-01

    Full Text Available Non-host resistance is the most ample and durable form of plant resistance against pathogen infection. It includes induction of defense-associated genes, massive metabolic reprogramming, and in many instances, a form of localized cell death (LCD at the site of infection, purportedly designed to limit the spread of biotrophic and hemibiotrophic microorganisms. Reactive oxygen species (ROS have been proposed to act as signals for LCD orchestration. They are produced in various cellular compartments including chloroplasts, mitochondria and apoplast. We have previously reported that down-regulation of ROS build-up in chloroplasts by expression of a plastid-targeted flavodoxin (Fld suppressed LCD in tobacco leaves inoculated with the non-host bacterium Xanthomonas campestris pv. vesicatoria (Xcv, while other defensive responses were unaffected, suggesting that chloroplast ROS and/or redox status play a major role in the progress of LCD. To better understand these effects, we compare here the transcriptomic alterations caused by Xcv inoculation on leaves of Fld-expressing tobacco plants and their wild-type siblings. About 29% of leaf-expressed genes were affected by Xcv and/or Fld. Surprisingly, 5.8% of them (1,111 genes were regulated by Fld in the absence of infection, presumably representing pathways responsive to chloroplast ROS production and/or redox status during normal growth conditions. While the majority (∼75% of pathogen-responsive genes were not affected by Fld, many Xcv responses were exacerbated, attenuated, or regulated in opposite direction by expression of this protein. Particularly interesting was a group of 384 genes displaying Xcv responses that were already triggered by Fld in the absence of infection, suggesting that the transgenic plants had a larger and more diversified suite of constitutive defenses against the attacking microorganism compared to the wild type. Fld modulated many genes involved in pathogenesis, signal

  7. Late-onset running biphasically improves redox balance, energy- and methylglyoxal-related status, as well as SIRT1 expression in mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Stefano Falone

    Full Text Available Despite the active research in this field, molecular mechanisms underlying exercise-induced beneficial effects on brain physiology and functions are still matter of debate, especially with regard to biological processes activated by regular exercise affecting the onset and progression of hippocampal aging in individuals unfamiliar with habitual physical activity. Since such responses seem to be mediated by changes in antioxidative, antiglycative and metabolic status, a possible exercise-induced coordinated response involving redox, methylglyoxal- and sirtuin-related molecular networks may be hypothesized. In this study, hippocampi of CD1 mice undergoing the transition from mature to middle age were analyzed for redox-related profile, oxidative and methylglyoxal-dependent damage patterns, energy metabolism, sirtuin1 and glyoxalase1 expression after a 2- or 4-mo treadmill running program. Our findings suggested that the 4-mo regular running lowered the chance of dicarbonyl and oxidative stress, activated mitochondrial catabolism and preserved sirtuin1-related neuroprotection. Surprisingly, the same cellular pathways were negatively affected by the first 2 months of exercise, thus showing an interesting biphasic response. In conclusion, the duration of exercise caused a profound shift in the response to regular running within the rodent hippocampus in a time-dependent fashion. This research revealed important details of the interaction between exercise and mammal hippocampus during the transition from mature to middle age, and this might help to develop non-pharmacological approaches aimed at retarding brain senescence, even in individuals unfamiliar with habitual exercise.

  8. Penconazole alters redox status, cholinergic function and lung's histoarchitecture of adult rats: Reversal effect of vitamin E.

    Science.gov (United States)

    Chaâbane, Mariem; Elwej, Awatef; Ghorbel, Imen; Chelly, Sabrine; Mnif, Hela; Boudawara, Tahia; Ellouze Chaabouni, Semia; Zeghal, Najiba; Soudani, Nejla

    2018-06-01

    The present study pertains to the possible adverse effects of penconazole exposure on the lung of adult rats, and to the potential ability of vitamin E (Vit E) in mitigating the toxicity induced by this fungicide. Male Wistar rats were divided into four groups of six animals each: Group I (Controls): rats drank distilled water; Group II (PEN): rats received, by gavage, 50 mg/kg body weight (1/40 LD 50 ) of penconazole every 2 days during 10 days; Group III (Vit E): rats received daily 100 mg α-tocopherol acetate/kg body weight during 10 days by gavage; and Group IV (Vit E + PEN): rats received both vitamin E (100 mg α-tocopherol acetate/kg body weight) and penconazole (50 mg/kg body weight), being vitamin E given as a daily dosage and penconazole every 2 days, by gavage during 10 days. Results showed that penconazole induced oxidative stress in the lung demonstrated by an increase in malondialdehyde (+77%), hydrogen peroxide (+58%) and advanced oxidation protein product (+22%) levels, as compared to the controls. Furthermore, a decrease in the activities of catalase (-41%), superoxide dismutase (-45%), glutathione peroxidase (-23%) and acetylcholinesterase (-67%), and an increase in the levels of non-protein thiols (+17%), glutathione (+7%) and vitamin C (+44%) were registered. Abnormalities in lung histological sections such as alveolar edema, infiltration of inflammatory cells (leukocytes) and emphysema, were also observed following penconazole exposure. Vitamin E ameliorated the biochemical parameters, as well as the histological impairments induced by this fungicide. In conclusion, our study demonstrated that vitamin E, a natural antioxidant, was effective in alleviating penconazole-induced lung damage in Wistar rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. Barium chloride induces redox status unbalance, upregulates cytokine genes expression and confers hepatotoxicity in rats-alleviation by pomegranate peel.

    Science.gov (United States)

    Elwej, Awatef; Grojja, Yousri; Ghorbel, Imen; Boudawara, Ons; Jarraya, Raoudha; Boudawara, Tahia; Zeghal, Najiba

    2016-04-01

    The present study was performed to establish the therapeutic efficacy of pomegranate peel against barium chloride induced liver injury. Adult rats were divided into four groups of six animals each: group I, serving as controls, received distilled water; group II received by their drinking water 67 ppm of BaCl2; group III received both 67 ppm of BaCl2 by the same way than group II and 5 % of pomegranate peel (PP) via diet; group IV received 5 % of PP. Analysis by HPLC/MS of PP showed its rich composition in flavonoids such as gallic acid, castalin, hyperin, quercitrin, syringic acid, and quercetin. The protective effects of pomegranate peel against hepatotoxicity induced by barium chloride were assessed using biochemical parameters and histological studies. Exposure of rats to barium caused oxidative stress in the liver as evidenced by an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOHs), H2O2 and advanced oxidation protein product (AOPP) levels, and lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities, a decrease in catalase (CAT) and glutathione peroxidase (GPx) activities, glutathion (GSH), non-protein thiol (NPSH), vitamin C levels, and Mn-SOD gene expression. Liver total MT levels, MT-1, and MT-2 and pro-inflammatory cytokine genes expression like TNF-α, IL-1β and IL-6 were increased. Pomegranate peel, supplemented in the diet of barium-treated rats, showed an improvement of all the parameters indicated above.The present work provided ethnopharmacological relevance of pomegranate peel against the toxic effects of barium, suggesting its beneficial role as a potential antioxidant.

  10. Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status.

    Science.gov (United States)

    Huang, Xianfeng; Liu, Yuanyuan; Lu, Yingxun; Ma, Chunhua

    2015-05-01

    Acute lung injury (ALI) represents a clinical syndrome that results from complex responses of the lung to a multitude of direct and indirect insults. This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings suggest that the protective mechanism of EUL may be attributed partly to decreased production of proinflammatory cytokines through the regulating inflammation and redox status. The results support that use of EUL is beneficial in the treatment of ALI. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Glutathione--linking cell proliferation to oxidative stress.

    Science.gov (United States)

    Diaz-Vivancos, Pedro; de Simone, Ambra; Kiddle, Guy; Foyer, Christine H

    2015-12-01

    The multifaceted functions of reduced glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) continue to fascinate plants and animal scientists, not least because of the dynamic relationships between GSH and reactive oxygen species (ROS) that underpin reduction/oxidation (redox) regulation and signalling. Here we consider the respective roles of ROS and GSH in the regulation of plant growth, with a particular focus on regulation of the plant cell cycle. Glutathione is discussed not only as a crucial low molecular weight redox buffer that shields nuclear processes against oxidative challenge but also a flexible regulator of genetic and epigenetic functions. The intracellular compartmentalization of GSH during the cell cycle is remarkably consistent in plants and animals. Moreover, measurements of in vivo glutathione redox potentials reveal that the cellular environment is much more reducing than predicted from GSH/GSSG ratios measured in tissue extracts. The redox potential of the cytosol and nuclei of non-dividing plant cells is about -300 mV. This relatively low redox potential maintained even in cells experiencing oxidative stress by a number of mechanisms including vacuolar sequestration of GSSG. We propose that regulated ROS production linked to glutathione-mediated signalling events are the hallmark of viable cells within a changing and challenging environment. The concept that the cell cycle in animals is subject to redox controls is well established but little is known about how ROS and GSH regulate this process in plants. However, it is increasingly likely that redox controls exist in plants, although possibly through different pathways. Moreover, redox-regulated proteins that function in cell cycle checkpoints remain to be identified in plants. While GSH-responsive genes have now been identified, the mechanisms that mediate and regulate protein glutathionylation in plants remain poorly defined. The nuclear GSH pool provides an appropriate redox environment

  12. Maintenance of Macrophage Redox Status by ChREBP Limits Inflammation and Apoptosis and Protects against Advanced Atherosclerotic Lesion Formation

    Directory of Open Access Journals (Sweden)

    Vincent Sarrazy

    2015-10-01

    Full Text Available Enhanced glucose utilization can be visualized in atherosclerotic lesions and may reflect a high glycolytic rate in lesional macrophages, but its causative role in plaque progression remains unclear. We observe that the activity of the carbohydrate-responsive element binding protein ChREBP is rapidly downregulated upon TLR4 activation in macrophages. ChREBP inactivation refocuses cellular metabolism to a high redox state favoring enhanced inflammatory responses after TLR4 activation and increased cell death after TLR4 activation or oxidized LDL loading. Targeted deletion of ChREBP in bone marrow cells resulted in accelerated atherosclerosis progression in Ldlr−/− mice with increased monocytosis, lesional macrophage accumulation, and plaque necrosis. Thus, ChREBP-dependent macrophage metabolic reprogramming hinders plaque progression and establishes a causative role for leukocyte glucose metabolism in atherosclerosis.

  13. Glutathione level and its relation to radiation therapy in patients with cancer of uterine cervix

    International Nuclear Information System (INIS)

    Mukundan, H.; Bahadur, A.K.; Kumar, A.; Sardana, S.; Naik, S.L.D.; Ray, A.; Sharma, B.K.

    1999-01-01

    Glutathione functions as an important antioxidant in the destruction of hydrogen peroxide and lipid peroxides by providing substrate for the glutathione peroxidase and also promotes the ascorbic acid. Glutathione plays a vital role in detoxification of xenobiotics, carcinogens, free radicals and maintenance of immune functions. The study was aimed to determine plasma glutathione as well as erythrocyte glutathione and glutathione peroxidase in patients with invasive cervical carcinoma (n=30) before initiation and after completion of radiotherapy and subsequently, at the time of first three monthly follow-up visit. The levels of plasma glutathione, erythrocyte glutathione and glutathione peroxidase activity were found to be lower in all cervical cancer patients as compared to age matched normal control women. The study indicates a change in antioxidant status in relation with the glutathione system among patients with invasive carcinoma of the uterine cervix. This study also demonstrates the effect of radiation therapy on this antioxidant system. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Emodin Prevents Intrahepatic Fat Accumulation, Inflammation and Redox Status Imbalance During Diet-Induced Hepatosteatosis in Rats

    Directory of Open Access Journals (Sweden)

    Valerio Nobili

    2012-02-01

    Full Text Available High-fat and/or high-carbohydrate diets may predispose to several metabolic disturbances including liver fatty infiltration (hepatosteatosis or be associated with necro-inflammation and fibrosis (steatohepatitis. Several studies have emphasized the hepatoprotective effect of some natural agents. In this study, we investigated the potential therapeutic effects of the treatment with emodin, an anthraquinone derivative with anti-oxidant and anti-cancer abilities, in rats developing diet-induced hepatosteatosis and steatohepatitis. Sprague-Dawley rats were fed a standard diet (SD for 15 weeks, or a high-fat/high-fructose diet (HFD/HF. After 5 weeks, emodin was added to the drinking water of some of the SD and HFD/HF rats. The experiment ended after an additional 10 weeks. Emodin-treated HFD/HF rats were protected from hepatosteatosis and metabolic derangements usually observed in HFD/HF animals. Furthermore, emodin exerted anti-inflammatory activity by inhibiting the HFD/HF-induced increase of tumor necrosis factor (TNF-α. Emodin also affected the hepatocytes glutathione homeostasis and levels of the HFD/HF-induced increase of glutathionylated/phosphorylated phosphatase and tensin homolog (PTEN. In conclusion, we demonstrated that a natural agent such as emodin can prevent hepatosteatosis, preserving liver from pro-inflammatory and pro-oxidant damage caused by HFD/HF diet. These findings are promising, proposing emodin as a possible hindrance to progression of hepatosteatosis into steatohepatitis.

  16. Regulatory redox state in tree seeds

    Directory of Open Access Journals (Sweden)

    Ewelina Ratajczak

    2017-12-01

    Full Text Available Peroxiredoxins (Prx are important regulators of the redox status of tree seeds during maturation and long-term storage. Thioredoxins (Trx are redox transmitters and thereby regulate Prx activity. Current research is focused on the association of Trx with Prx in tree seeds differing in the tolerance to desiccation. The results will allow for better understanding the regulation of the redox status in orthodox, recalcitrant, and intermediate seeds. The findings will also elucidate the role of the redox status during the loss of viability of sensitive seeds during drying and long-term storage.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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

  1. Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis.

    Science.gov (United States)

    Wiley, Sandra E; Andreyev, Alexander Y; Divakaruni, Ajit S; Karisch, Robert; Perkins, Guy; Wall, Estelle A; van der Geer, Peter; Chen, Yi-Fan; Tsai, Ting-Fen; Simon, Melvin I; Neel, Benjamin G; Dixon, Jack E; Murphy, Anne N

    2013-06-01

    Miner1 is a redox-active 2Fe2S cluster protein. Mutations in Miner1 result in Wolfram Syndrome, a metabolic disease associated with diabetes, blindness, deafness, and a shortened lifespan. Embryonic fibroblasts from Miner1(-/-) mice displayed ER stress and showed hallmarks of the unfolded protein response. In addition, loss of Miner1 caused a depletion of ER Ca(2+) stores, a dramatic increase in mitochondrial Ca(2+) load, increased reactive oxygen and nitrogen species, an increase in the GSSG/GSH and NAD(+)/NADH ratios, and an increase in the ADP/ATP ratio consistent with enhanced ATP utilization. Furthermore, mitochondria in fibroblasts lacking Miner1 displayed ultrastructural alterations, such as increased cristae density and punctate morphology, and an increase in O2 consumption. Treatment with the sulphydryl anti-oxidant N-acetylcysteine reversed the abnormalities in the Miner1 deficient cells, suggesting that sulphydryl reducing agents should be explored as a treatment for this rare genetic disease. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  2. Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

    Science.gov (United States)

    Yuan, Xiao-Hua; Lu, Cai-Ling; Yao, Nan; An, Li-Sha; Yang, Bai-Qing; Zhang, Chuan-Ling; Ma, Xu

    2012-01-01

    Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. Copyright © 2011 Wiley Periodicals, Inc.

  3. Lipoic acid and redox status in barley plants subjected to salinity and elevated CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Lopez, U.; Robredo, A.; Mena-Petite, A.; Munoz-Rueda, A. (Univ. del Pais Vasco/EHU, Dept. de Biologia Vegetal y Ecologia, Bilbao (Spain)); Lacuesta, M. (Univ. del Pais Vasco/EHU, Dept. de Biologia Vegetal y Ecologia, Vitoria-Gasteiz (Spain)); Sgherri, C.; Navari-Izzo, F. (Univ. di Pisa, Dipartimento di Chimica e Biotecnologie Agrarie, Pisa (Italy))

    2010-02-15

    Future environmental conditions will include elevated concentrations of salt in the soil and an elevated concentration of CO{sub 2}in the atmosphere. Because these environmental changes will likely affect reactive oxygen species (ROS) formation and cellular antioxidant metabolism in opposite ways, we analyzed changes in cellular H{sub 2}O{sub 2} and non-enzymatic antioxidant metabolite [lipoic acid (LA), ascorbate (ASA), glutathione (GSH)] content induced by salt stress (0, 80, 160 or 240 mM NaCl) under ambient (350 mumol mol-1) or elevated (700 mumol mol-1) CO{sub 2}concentrations in two barley cultivars (Hordeum vulgare L.) that differ in sensitivity to salinity (cv. Alpha is more sensitive than cv. Iranis). Under non-salinized conditions, elevated CO{sub 2}increased LA content, while ASA and GSH content decreased. Under salinized conditions and ambient CO{sub 2}, ASA increased, while GSH and LA decreased. At 240 mM NaCl, H{sub 2}O{sub 2} increased in Alpha and decreased in Iranis. When salt stress was imposed at elevated CO{sub 2}, less oxidative stress and lower increases in ASA were detected, while LA was constitutively higher. The decrease in oxidative stress could have been because of less ROS formation or to a higher constitutive LA level, which might have improved regulation of ASA and GSH reductions. Iranis had a greater capacity to synthesize ASA de novo and had higher constitutive LA content than did Alpha. Therefore, we conclude that elevated CO{sub 2}protects barley cultivars against oxidative damage. However, the magnitude of the positive effect is cultivar specific. (author)

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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...

  9. Uranyl complexes of glutathione

    Energy Technology Data Exchange (ETDEWEB)

    Marzotto, A [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi

    1977-01-01

    Dioxouranium(VI) complexes of the tripeptide glutathione having different molar ratios were prepared and studied by IR, PMR, electronic absorption and circular dichroism spectra. The results indicate that coordination occurs at the carboxylato groups, acting as monodentate ligands, whereas no significant interaction with the amino and sulfhydrylic groups takes place.

  10. Effects of consuming diets containing Agave tequilana dietary fibre and jamaica calyces on body weight gain and redox status in hypercholesterolemic rats.

    Science.gov (United States)

    Sáyago-Ayerdi, Sonia G; Mateos, Raquel; Ortiz-Basurto, Rosa I; Largo, Carlota; Serrano, José; Granado-Serrano, Ana Belén; Sarriá, Beatriz; Bravo, Laura; Tabernero, María

    2014-04-01

    Dietary fibre (DF) obtained from Agave tequilana, which is rich in fructans and insoluble DF, and jamaica calyces (Hibiscus sabdariffa), which is rich in DF and phenolic compounds, were assessed as new potential functional ingredients using the hypercholesterolemic animal model. Wistar rats (200-250 g) were divided into 3 groups (n=8) and fed with cholesterol-rich diets supplemented with cellulose (CC, control), agave DF (ADF) or ADF with jamaica calyces (ADF-JC). After consuming the test diets for 5 weeks, weight gain in the ADF-JC group was significantly lower than in the other groups. The ADF and ADF-JC groups had a reduced concentration of cholesterol transporters in the caecum tissue, although no changes were observed in the plasma lipid profile. Both treatments improved the redox status by reducing the malondialdehyde serum levels and protein oxidative damage, compared to the CC group. DF from A. tequilana alone, or in combination with jamaica calyces, shows promising potential as a bioactive ingredient. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. The Effects of an Olive Fruit Polyphenol-Enriched Yogurt on Body Composition, Blood Redox Status, Physiological and Metabolic Parameters and Yogurt Microflora.

    Science.gov (United States)

    Georgakouli, Kalliopi; Mpesios, Anastasios; Kouretas, Demetrios; Petrotos, Konstantinos; Mitsagga, Chrysanthi; Giavasis, Ioannis; Jamurtas, Athanasios Z

    2016-06-03

    In the present study we investigated the effects of an olive polyphenol-enriched yogurt on yogurt microflora, as well as hematological, physiological and metabolic parameters, blood redox status and body composition. In a randomized double-blind, crossover design, 16 (6 men, 10 women) nonsmoking volunteers with non-declared pathology consumed either 400 g of olive fruit polyphenol-enriched yogurt with 50 mg of encapsulated olive polyphenols (experimental condition-EC) or 400 g of plain yogurt (control condition-CC) every day for two weeks. Physiological measurements and blood collection were performed before and after two weeks of each condition. The results showed that body weight, body mass index, hip circumference and systolic blood pressure decreased significantly (p yogurt regardless of condition. A tendency towards significance for decreased levels of low density lipoprotein (LDL) cholesterol (p = 0.06) and thiobarbituric acid reactive substances (p yogurt consumption was observed. The population of lactic acid bacteria (LAB) and production of lactate in yogurt were significantly enhanced after addition of olive polyphenols, contrary to the population of yeasts and molds. The results indicate that consumption of the polyphenol-enriched yogurt may help individuals with non-declared pathology reduce body weight, blood pressure, LDL cholesterol levels and lipid peroxidation, and promote growth of beneficial LAB.

  12. The Effects of an Olive Fruit Polyphenol-Enriched Yogurt on Body Composition, Blood Redox Status, Physiological and Metabolic Parameters and Yogurt Microflora

    Directory of Open Access Journals (Sweden)

    Kalliopi Georgakouli

    2016-06-01

    Full Text Available In the present study we investigated the effects of an olive polyphenol-enriched yogurt on yogurt microflora, as well as hematological, physiological and metabolic parameters, blood redox status and body composition. In a randomized double-blind, crossover design, 16 (6 men, 10 women nonsmoking volunteers with non-declared pathology consumed either 400 g of olive fruit polyphenol-enriched yogurt with 50 mg of encapsulated olive polyphenols (experimental condition—EC or 400 g of plain yogurt (control condition—CC every day for two weeks. Physiological measurements and blood collection were performed before and after two weeks of each condition. The results showed that body weight, body mass index, hip circumference and systolic blood pressure decreased significantly (p < 0.05 following the two-week consumption of yogurt regardless of condition. A tendency towards significance for decreased levels of low density lipoprotein (LDL cholesterol (p = 0.06 and thiobarbituric acid reactive substances (p < 0.05 following two weeks of polyphenol-enriched yogurt consumption was observed. The population of lactic acid bacteria (LAB and production of lactate in yogurt were significantly enhanced after addition of olive polyphenols, contrary to the population of yeasts and molds. The results indicate that consumption of the polyphenol-enriched yogurt may help individuals with non-declared pathology reduce body weight, blood pressure, LDL cholesterol levels and lipid peroxidation, and promote growth of beneficial LAB.

  13. Taurine, glutathione and bioenergetics

    DEFF Research Database (Denmark)

    Hansen, Svend Høime; Grunnet, Niels

    2013-01-01

    the mitochondrial inner-membrane. The very high concentration of taurine in oxidative tissue has recently led to discussions on the role of taurine in the mitochondria, e.g. with taurine acting as a pH buffer in the mitochondrial matrix. A very important consequence of the slightly alkaline pH is the fact...... to be independent of the matrix pH. Finally a simplified model for mitochondrial oxidation is presented with introduction of GSH as redox buffer to stabilise the electrical gradient, and taurine as pH buffer stabilising the pH gradient, but simultaneously establishing the equilibrium between the NADH/NAD(+) redox...

  14. Effect of Omega-3 and Vitamins E + C Supplements on the Concentration of Serum B-Vitamins and Plasma Redox Aminothiol Antioxidant Status in Elderly Men after Strength Training for Three Months.

    Science.gov (United States)

    Stea, Tonje Holte; Stølevik, Solvor B; Berntsen, Sveinung; Ezzathkah Bastani, Nasser; Paulsen, Gøran; Lohne Seiler, Hilde; Hetlelid, Ken J; Blomhoff, Rune; Mansoor, Mohammad Azam

    2016-01-01

    Data on redox plasma aminothiol status in individuals on strength training are very limited. Therefore, we studied the effect of omega-3 and vitamins E + C supplementation on the concentration of B-vitamins and redox aminothiol status in elderly men after strength training for 3 months. Healthy men, age 60 ± 6 (mean ± SD) were randomly divided into 3 groups: group I received placebo (n = 17), group II consumed omega-3 (700 mg, n = 17), and group III consumed vitamins E + C (235 mg +1 g, n = 16) daily for 3 months. All participants completed a strength training program for the same period. The concentration of serum vitamin B12 decreased and the concentration of serum folate increased in group I after the intervention (p = 0.01, p = 0.009). The concentration of plasma 5-pyridoxal phosphate decreased in groups II and III (p = 0.03 and p = 0.01), whereas the concentration of serum uric acid decreased only in group II (p = 0.02). We detected an increase in the concentration of reduced form of aminothiols in all groups (p vitamins E + C supplementation affect the concentrations of serum B-vitamins and redox plasma aminothiol status in healthy elderly men on strength training. © 2016 S. Karger AG, Basel.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Polyalthia longifolia Methanolic Leaf Extracts (PLME) induce apoptosis, cell cycle arrest and mitochondrial potential depolarization by possibly modulating the redox status in hela cells.

    Science.gov (United States)

    Vijayarathna, Soundararajan; Oon, Chern Ein; Chen, Yeng; Kanwar, Jagat R; Sasidharan, Sreenivasan

    2017-05-01

    Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC 50 ) and pro-oxidant (IC 50 and double IC 50 ) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC 50 concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Baseline Glutathione Peroxidase Activity Affects Prognosis after Acute Coronary Syndromes

    OpenAIRE

    García-Pinilla, José Manuel; Gálvez, Julio; Cabrera-Bueno, Fernando; Jiménez-Navarro, Manuel; Gómez-Doblas, Juan José; Galisteo, Milagros; Camuesco, Desiré; de Teresa Galván, Carlos; Espinosa-Caliani, Salvador; Zarzuelo, Antonio; de Teresa-Galván, Eduardo

    2008-01-01

    Oxidative stress is associated with atherosclerosis and plaque lesions in experimental in vitro models. Few in vivo studies have examined the association between redox status and the prognosis of acute coronary syndromes.

  18. Acute Exercise Increases Plasma Total Antioxidant Status and Antioxidant Enzyme Activities in Untrained Men

    Directory of Open Access Journals (Sweden)

    C. Berzosa

    2011-01-01

    Full Text Available Antioxidant defences are essential for cellular redox regulation. Since free-radical production may be enhanced by physical activity, herein, we evaluated the effect of acute exercise on total antioxidant status (TAS and the plasma activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase and its possible relation to oxidative stress resulting from exercise. Healthy untrained male subjects (=34 performed three cycloergometric tests, including maximal and submaximal episodes. Venous blood samples were collected before and immediately after each different exercise. TAS and enzyme activities were assessed by spectrophotometry. An increase of the antioxidant enzyme activities in plasma was detected after both maximal and submaximal exercise periods. Moreover, under our experimental conditions, exercise also led to an augmentation of TAS levels. These findings are consistent with the idea that acute exercise may play a beneficial role because of its ability to increase antioxidant defense mechanisms through a redox sensitive pathway.

  19. Redox pioneer:Professor Christine Helen Foyer.

    Science.gov (United States)

    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.

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Wassana Jamnongkan

    2018-01-01

    Full Text Available Cholangiocarcinoma (CCA caused by infection of the liver fluke Opisthorchis viverrini, (Ov is the major public health problem in northeast Thailand. Following Ov infection the subsequent molecular changes can be associated by reactive oxygen species (ROS induced chronic inflammation, advanced periductal fibrosis, and cholangiocarcinogenesis. Notably, resistance to an activation of cell death in prolonged oxidative stress conditions can occur but some damaged/mutated cells could survive and enable clonal expansion. Our study used a natural product, xanthohumol (XN, which is an anti-oxidant and anti-inflammatory compound, to examine whether it could prevent Ov-associated CCA carcinogenesis. We measured the effect of XN with or without praziquantel (PZ, an anti-helminthic treatment, on DNA damage, redox status change including iron accumulation and periductal fibrosis during CCA genesis induced by administration of Ov and N-dinitrosomethylamine (NDMA in hamsters. Animals were randomly divided into four groups: group I, Ov infection and NDMA administration (ON; group II, Ov infection and NDMA administration and PZ treatment (ONP; the latter 2 groups were similar to group I and II, but group III received additional XN (XON and group IV received XN plus PZ (XONP. The results showed that high 8-oxodG (a marker of DNA damage was observed throughout cholangiocarcinogenesis. Moreover, increased expression of CD44v8-10 (a cell surface in regulation of the ROS defense system, whereas decreased expression of phospho-p38MAPK (a major ROS target, was found during the progression of the bile duct cell transformation. In addition, high accumulation of iron and expression of transferrin receptor-1 (TfR-1 in both malignant bile ducts and inflammatory cells were detected. Furthermore, fibrosis also increased with the highest level being on day 180. On the other hand, the groups of XN with or without PZ supplementations showed an effective reduction in all the

  6. 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

  7. 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...

  8. Human semen as an early, sensitive biomarker of highly polluted living environment in healthy men: A pilot biomonitoring study on trace elements in blood and semen and their relationship with sperm quality and RedOx status.

    Science.gov (United States)

    Bergamo, Paolo; Volpe, Maria Grazia; Lorenzetti, Stefano; Mantovani, Alberto; Notari, Tiziana; Cocca, Ennio; Cerullo, Stefano; Di Stasio, Michele; Cerino, Pellegrino; Montano, Luigi

    2016-12-01

    The Campania region in Italy is facing an environmental crisis due to the illegal disposal of toxic waste. Herein, a pilot study (EcoFoodFertility initiative) was conducted to investigate the use of human semen as an early biomarker of pollution on 110 healthy males living in various areas of Campania with either high or low environmental impact. The semen from the "high impact" group showed higher zinc, copper, chromium and reduced iron levels, as well as reduced sperm motility and higher sperm DNA Fragmentation Index (DFI). Redox biomarkers (total antioxidant capacity, TAC, and glutathione, GSH) and the activity of antioxidant enzymes in semen were lower in the "high impact" group. The percentage of immotile spermatozoa showed a significant inverse correlation with TAC and GSH. Overall, several semen parameters (reduced sperm quality and antioxidant defenses, altered chemical element pattern), which were associated with residence in a high polluted environment, could be used in a further larger scale study, as early biomarkers of environmental pollution. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Infestation of potato (Solanum tuberosum L.) by the peach-potato aphid (Myzus persicae Sulzer) alters cellular redox status and is influenced by ascorbate.

    Science.gov (United States)

    Kerchev, Pavel I; Fenton, Brian; Foyer, Christine H; Hancock, Robert D

    2012-02-01

    The peach-potato aphid (Myzus persicae Sulzer) is a major pest of potato (Solanum tuberosum L.) but the molecular characterization of this interaction particularly with regard to oxidants and antioxidants remains to be undertaken. Aphid colonies reared on potato leaves containing high ascorbate were twice the size of those grown on leaves with low ascorbate. Infestation-dependent decreases in the abundance of key transcripts such as chloroplastic FeSOD, peroxisomal catalase 2, PR1 and JAZ1 preceded detectable leaf H(2)O(2) or polyphenol accumulation. The leaf glutathione pool was increased 48 h after infestation, but the amount of ascorbate was unchanged. The ascorbate/dehydroacorbate (DHA) ratio was lower at 48 h but the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) was unchanged. While DHA reductase and GSSG reductase activities were unaffected by aphid feeding, non-specific peroxidase activities were enhanced 48 h following aphid infestation. Brown ethanol-insoluble deposits were observed close to leaf veins following aphid infestation. Taken together, the results demonstrate that high ascorbate favours aphid colony expansion and that perturbations in the leaf antioxidant system are intrinsic to the potato leaf response to aphids. Moreover, these changes together with the induction of hormone-related transcripts precede the deposition of defence-associated oxidized polyphenols along the stylet track. © 2011 Blackwell Publishing Ltd.

  10. Double-blind randomised controlled trial of the independent and synergistic effect of Spirulina maxima with exercise (ISESE) on general fitness, lipid profile and redox status in overweight and obese subjects: study protocol.

    Science.gov (United States)

    Hernández-Lepe, Marco Antonio; López-Díaz, José Alberto; Rosa, Laura Alejandra de la; Hernández-Torres, Rosa Patricia; Wall-Medrano, Abraham; Juarez-Oropeza, Marco Antonio; Pedraza-Chaverri, José; Urquidez-Romero, Rene; Ramos-Jiménez, Arnulfo

    2017-06-23

    In order to reduce cardiovascular disease risk factors, a healthy diet must include dietary antioxidants from different sources (eg, Spirulina maxima ) and regular practice of exercise should be promoted. There is some evidence from animal studies that S. maxima and exercise decrease cardiovascular disease risks factors. However, very few studies have proved the independent or synergistic effect of S. maxima plus exercise in humans. This study attempts to address the independent and synergistic effects in overweight and obese subjects participating in a systematic physical exercise programme at moderate intensity on general fitness, plasma lipid profile and antioxidant capacity. Using a randomised, double-blind, placebo-controlled, counterbalanced crossover study design, 80 healthy overweight and obese subjects will be evaluated during a 12-week isoenergetic diet accompanied by 4.5 g/day S. maxima intake and/or a physical systematic exercise programme at moderate intensity. Body composition, oxygen uptake, heart rate, capillary blood lactate, plasma concentrations of triacylglycerols, total, low-density and high-density lipoprotein cholesterol, antioxidant status, lipid oxidation, protein carbonyls, superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione reductase and paraoxonase will be assessed. This study and all the procedures have been approved by the Universidad Autonoma de Ciudad Juarez Bioethics Committee. Findings will be disseminated through peer-reviewed journals, national and international conferences. ClinicalTrials.gov: NCT02837666. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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).

  16. 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.

  17. NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

    2018-05-26

    Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

  18. 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.

  19. 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....

  20. 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...

  1. 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, ...

  2. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Influence of Curcumin on the Redox System and Lipid Peroxidation in Gamma Irradiated Rats

    International Nuclear Information System (INIS)

    Zahran, A.M.

    2007-01-01

    Naturally occurring micro nutrients polyphenolic compounds have received increased attention in the maintenance of health. Curcumin, the main active biological phyto chemical constituents of Turmeric (Curcuma longa L. rhizomes), is known for its wide range of medicinal properties. The present study was designed to evaluate the potential efficacy of curcumin administration against redox imbalance state and cytotoxic induced by protracted exposure to 'y-rays. Curcumin was orally administered to Sprague Dawley male albino rats simultaneously via intragastric intubation (80 mg/ Kg body wt) for 7 days before exposure to gamma- rays and continued during the whole period of irradiation processing. Whole body γ-rays was delivered as fractionated doses (3 weeks) 3 Gy increment every week up to total cumulative dose of (9 Gy). The results obtained showed increased level of lipid peroxides contents and xanthine oxidase (XO) activity in irradiated animal groups with concomitant depletion in the level of reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSFI-Px). Administration of curcumin has significantly lowered the level of lipid peroxidation and enhanced the antioxidant status of irradiated animals. It could he concluded that curcumin exerts a protective effect against radiation-induced cytotoxic by modulating the extent of lipid peroxidation and augmenting antioxidant defence system

  4. 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...

  5. Glutathione as a radical scavenger and the biological consequences of thiyl radical production

    International Nuclear Information System (INIS)

    Winterbourn, C.C.

    1996-01-01

    A large number of compounds that have toxic effects can be metabolised to free radicals and secondary reactive oxygen species. These may be directly damaging or affect cell function by altering regulatory mechanisms through changing redox status. Protection is provided by an integrated system of antioxidant defenses. This includes reduced glutathione (GSH), one of the functions of which is as a free radical scavenger. For GSH to be an effective radical scavenging antioxidant, therefore, it must act in concert with superoxide dismutase to remove the superoxide so generated. Superoxide is produced in a variety of metabolic processes. It is also a secondary product of radicals reacting with oxygen either directly or through GSH. The biological reactivity of superoxide has been the subject of much debate ever since the discovery of superoxide dismutase in 1968. It has more recently become apparent that its rapid reaction with nitric oxide to give peroxynitrite, and its ability to reversibly oxidise and inactivate iron sulphur enzymes, contribute to the toxicity of superoxide. Another mechanism that could be important involves addition reactions of superoxide with other radicals to give organic peroxides. This reaction, to form a tyrosine peroxide, has come to authors attention through the study of the scavenging of tyrosyl radicals by GSH. It is also shown that a tyrosine peroxide is a major product of the oxidation of tyrosine by neutrophils

  6. Unusual thiol-based redox metabolism of parasitic flukes.

    Science.gov (United States)

    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.

  7. Ciprofloxacin provokes SOS-dependent changes in respiration and membrane potential and causes alterations in the redox status of Escherichia coli.

    Science.gov (United States)

    Smirnova, Galina V; Tyulenev, Aleksey V; Muzyka, Nadezda G; Peters, Mikhail A; Oktyabrsky, Oleg N

    2017-01-01

    An in-depth understanding of the physiological response of bacteria to antibiotic-induced stress is needed for development of new approaches to combatting microbial infections. Fluoroquinolone ciprofloxacin causes phase alterations in Escherichia coli respiration and membrane potential that strongly depend on its concentration. Concentrations lower than the optimal bactericidal concentration (OBC) do not inhibit respiration during the first phase. A dose higher than the OBC provokes immediate SOS-independent inhibition of respiration and growth that can contribute to a decreased SOS response and lowered susceptibility to high concentrations of ciprofloxacin. Cells retain their metabolic activity, membrane potential and accelerated K + uptake and produce low levels of superoxide and H 2 O 2 during the first phase. The time before initiation of the second phase is inversely correlated with the ciprofloxacin concentration. The second phase is SOS-dependent and characterized by respiratory inhibition, membrane depolarization, K + and glutathione leakage and cessation of glucose consumption and may be considered as cell death. atpA, gshA and kefBkefC knockouts, which perturb fluxes of protons and K + , can modify the degree and duration of respiratory inhibition and potassium retention. Loss of K + efflux channels KefB and KefC enhances the susceptibility of E. coli to ciprofloxacin. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. Glutathione treatment of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Ranek, L; Mantoni, M

    1992-01-01

    This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH...

  9. 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 ...

  10. 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

  11. Hepatic glutathione and glutathione S-transferase in selenium deficiency and toxicity in the chick

    International Nuclear Information System (INIS)

    Kim, Y. S.

    1989-01-01

    First, the hepatic activity of GSH-T CDNB was increased only under conditions of severe oxidative stress produced by combined Se- and vitamin E (VE)-deficiency, indicating that VE also affects GSH metabolism. Second, the incorporation of 35 S-methionine into GSH and protein was about 4- and 2-fold higher, respectively, in Se- and VE-deficient chick hepatocytes as compared to controls. Third, chicks injected with the glutathione peroxidase (SeGSHpx) inhibitor, aurothioglucose (AuTG), showed increase hepatic GSH-T CDNB activity and plasma GSH concentration regardless of their Se status. Fourth, the effect of ascorbic acid (AA), on GSH metabolism was studied. Chicks fed 1000 ppm AA showed decreased hepatic GSH concentration compared to chicks fed no AA in a Se- and VE-deficient diet. Fifth, chicks fed excess Se showed increase hepatic activity of GSH-T CDNB and GSH concentration regardless of VE status

  12. [Alternative nutrition and glutathione levels].

    Science.gov (United States)

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Brtková, A; Magálová, T; Barteková, S

    1999-08-30

    Low protein quality and quantity is reported to be a possible risk of alternative nutrition. Pulses contain 18-41% of methionine in relation to reference protein, moreover, its content in cereals is by one half lower. Therefore vegetarians and vegans may have an insufficient intake of sulphur-containing amino acids that may subsequently affect glutathione values (precursors of its synthesis). In groups of adults on an alternative diet--lactoovovegetarians (n = 47) and vegans (n = 44) aged 19-62 years with average duration on a vegetarian or vegan diet of 7.6 and 4.9 years, respectively, glutathione levels (GSH) were measured in erythrocytes (spectrophotometrically), as well as the activity of GSH-dependent enzymes. As nutritional control (n = 42) served an average sample of omnivores selected from a group of 489 examined, apparently healthy subjects of the same age range living in the same region. One to low protein intake (56% of RDA) exclusively of plant origin significantly lower levels of total proteins were observed in vegans with a 16% frequency of hypoproteinaemia (vs 0% in omnivores). In comparison to omnivores a significantly lower glutathione level was found (4.28 +/- 0.12 vs 4.84 +/- 0.14 mumol/g Hb, P vegan diet also in adult age.

  13. Redox signaling in plants.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham

    2013-06-01

    Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental constraints and cues. Plants produce significant amounts of singlet oxygen and other reactive oxygen species (ROS) as a result of photosynthetic electron transport and metabolism. Such pathways contribute to the compartment-specific redox-regulated signaling systems in plant cells that convey information to the nucleus to regulate gene expression. Like the chloroplasts and mitochondria, the apoplast-cell wall compartment makes a significant contribution to the redox signaling network, but unlike these organelles, the apoplast has a low antioxidant-buffering capacity. The respective roles of ROS, low-molecular antioxidants, redox-active proteins, and antioxidant enzymes are considered in relation to the functions of plant hormones such as salicylic acid, jasmonic acid, and auxin, in the composite control of plant growth and defense. Regulation of redox gradients between key compartments in plant cells such as those across the plasma membrane facilitates flexible and multiple faceted opportunities for redox signaling that spans the intracellular and extracellular environments. In conclusion, plants are recognized as masters of the art of redox regulation that use oxidants and antioxidants as flexible integrators of signals from metabolism and the environment.

  14. Involvement of histone H3 phosphorylation via the activation of p38 MAPK pathway and intracellular redox status in cytotoxicity of HL-60 cells induced by Vitex agnus-castus fruit extract.

    Science.gov (United States)

    Kikuchi, Hidetomo; Yuan, Bo; Yuhara, Eisuke; Imai, Masahiko; Furutani, Ryota; Fukushima, Shin; Hazama, Shingo; Hirobe, Chieko; Ohyama, Kunio; Takagi, Norio; Toyoda, Hiroo

    2014-08-01

    We have demonstrated that an extract from the ripe fruit of Vitex angus-castus (Vitex), might be a promising anticancer candidate. In order to further provide a molecular rationale for clinical development in anticancer therapy, a detailed mechanism underlying the efficacy of Vitex against HL-60 cells was investigated. Vitex induced a dose- and time-dependent decrease in cell viability associated with induction of apoptosis and G(2)/M cell cycle arrest, both of which were suppressed by the addition of SB203580, an inhibitor for p38 MAPK. Furthermore, SB203580 significantly suppressed Vitex-induced phosphorylation of histone H3, a downstream molecule of p38 MAPK known to be involved in apoptosis induction in tumor cells. Notably, Vitex induced upregulation of intracellular ATP, known to bind its binding pocket inside activated p38 MAPK and to be required for the activation of p38 MAPK pathway. These results, thus, suggest that upregulation of intracellular ATP and phosphorylation of histone H3 are closely associated with the activation of p38 MAPK pathway, consequently contributing to Vitex-mediated cytotoxicity. Intriguingly, a significant decrease of intracellular ROS levels and downregulation of expression level of gp91(phox), an important component of NADPH oxidase, were observed in Vitex-treated cells. A greater decline in ROS levels along with enhanced apoptosis was observed after treatment with Vitex in combination with SnPP, an inhibitor specific for HO-1. Since NADPH oxidase and HO-1 are closely correlated to redox status associated with intracellular ROS levels, the two enzymes are suggested to be implicated in Vitex-mediated cytotoxicity in HL-60 cells by regulating ROS generation. We also suggest that activation of the p38 MAPK pathway may be dependent on the alterations of intracellular ATP levels, rather than that of intracellular ROS levels. These results may have important implications for appropriate clinical uses of Vitex and provide novel insights

  15. 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)

  16. 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

  17. Impaired glutathione synthesis in schizophrenia

    DEFF Research Database (Denmark)

    Gysin, René; Kraftsik, Rudolf; Sandell, Julie

    2007-01-01

    Schizophrenia is a complex multifactorial brain disorder with a genetic component. Convergent evidence has implicated oxidative stress and glutathione (GSH) deficits in the pathogenesis of this disease. The aim of the present study was to test whether schizophrenia is associated with a deficit...... of GSH synthesis. Cultured skin fibroblasts from schizophrenia patients and control subjects were challenged with oxidative stress, and parameters of the rate-limiting enzyme for the GSH synthesis, the glutamate cysteine ligase (GCL), were measured. Stressed cells of patients had a 26% (P = 0.......002) decreased GCL activity as compared with controls. This reduction correlated with a 29% (P schizophrenia in two...

  18. Associations between Specific Redox Biomarkers and Age in a Large European Cohort: The MARK-AGE Project

    Directory of Open Access Journals (Sweden)

    Daniela Weber

    2017-01-01

    Full Text Available Oxidative stress and antioxidants play a role in age-related diseases and in the aging process. We here present data on protein carbonyls, 3-nitrotyrosine, malondialdehyde, and cellular and plasma antioxidants (glutathione, cysteine, ascorbic acid, uric acid, α-tocopherol, and lycopene and their relation with age in the European multicenter study MARK-AGE. To avoid confounding, only data from countries which recruited subjects from all three study groups (five of eight centers and only participants aged ≥55 years were selected resulting in data from 1559 participants. These included subjects from (1 the general population, (2 members from long-living families, and (3 their spouses. In addition, 683 middle-aged reference participants (35–54 years served as a control. After adjustment for age, BMI, smoking status, gender, and country, there were differences in protein carbonyls, malondialdehyde, 3-nitrotyrosine, α-tocopherol, cysteine, and glutathione between the 3 study groups. Protein carbonyls and 3-nitrotyrosine as well as cysteine, uric acid, and lycopene were identified as independent biomarkers with the highest correlation with age. Interestingly, from all antioxidants measured, only lycopene was lower in all aged groups and from the oxidative stress biomarkers, only 3-nitrotyrosine was increased in the descendants from long-living families compared to the middle-aged control group. We conclude that both lifestyle and genetics may be important contributors to redox biomarkers in an aging population.

  19. Mitochondrial Swelling Induced by Glutathione

    Science.gov (United States)

    Lehninger, Albert L.; Schneider, Marion

    1959-01-01

    Reduced glutathione, in concentrations approximating those occurring in intact rat liver, causes swelling of rat liver mitochondria in vitro which is different in kinetics and extent from that yielded by L-thyroxine. The effect is also given by cysteine, which is more active, and reduced coenzyme A, but not by L-ascorbate, cystine, or oxidized glutathione. The optimum pH is 6.5, whereas thyroxine-induced swelling is optimal at pH 7.5. The GSH-induced swelling is not inhibited by DNP or dicumarol, nor by high concentrations of sucrose, serum albumin, or polyvinylpyrrolidone, in contrast to thyroxine-induced swelling. ATP inhibits the GSH swelling, but ADP and AMP are ineffective. Mn-+ is a very potent inhibitor, but Mg++ is ineffective. Ethylenediaminetetraacetate is also an effective inhibitor of GSH-induced swelling. The respiratory inhibitors amytal and antimycin A do not inhibit the swelling action of GSH, but cyanide does; these findings are consistent with the view that the oxidation-reduction state of the respiratory chain between cytochrome c and oxygen is a determinant of GSH-induced swelling. Reversal of GSH-induced swelling by osmotic means or by ATP in KCl media could not be observed. Large losses of nucleotides and protein occur during the swelling by GSH, suggesting that the action is irreversible. The characteristically drastic swelling action of GSH could be prevented if L-thyroxine was also present in the medium. PMID:13630941

  20. Role of glutathione biosynthesis in endothelial dysfunction and fibrosis

    Directory of Open Access Journals (Sweden)

    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

  1. Inhibitory effect of glutathione on oxidative liver injury induced by dengue virus serotype 2 infections in mice.

    Directory of Open Access Journals (Sweden)

    Juan Wang

    Full Text Available The pathogenesis of dengue virus (DV infection has not been completely defined and change of redox status mediated by depletion of glutathione (GSH in host cell is a common result of viral infection. Our previous study has demonstrated that DV serotype 2 (DV2 infection alters host intracellular GSH levels, and exogenous GSH inhibits viral production by modulating the activity of NF-κB in HepG2 cells. GSH is the most powerful intracellular antioxidant and involved in viral infections. Thus, this study was to investigate whether DV2 infection can induce alteration in redox balance and effect of GSH on the disease in HepG2 xenografts SCID mice. Our results revealed that mice infected with DV2 showed alterations in oxidative stress by increasing the level of malondialdehyde (MDA, an end product of lipid peroxidation, and GSSG/GSH ratio. DV2-infected mice also showed a decrease in the activity of catalase (CAT and total superoxide dismutase (T-SOD in the serum and/or observed organs, especially the liver. Moreover, DV2 infection resulted in elevated serum levels of the cytokines tumor necrosis factor-α and interlukin-6 and obvious histopathological changes in the liver. The administration of exogenous GSH significantly reversed all of the aforementioned pathological changes and prevented significant liver damage. Furthermore, in vitro treatment of HepG2 cells with antioxidants such as GSH inhibited viral entry as well as the production of reactive oxygen species in HepG2 cells. These results suggest that GSH prevents DV2-induced oxidative stress and liver injury in mice by inhibiting proinflammatory cytokine production, and GSH and may be a promising therapeutic agent for prevention of oxidative liver damage during DV infection.

  2. 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.

  3. 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.

  4. Imaging Mitochondrial Redox Potential and Its Possible Link to Tumor Metastatic Potential

    Science.gov (United States)

    Li, Lin Z.

    2012-01-01

    Cellular redox states can regulate cell metabolism, growth, differentiation, motility, apoptosis, signaling pathways, and gene expressions etc. Growing body of literature suggest importance of redox status for cancer progression. While most studies on redox state were done on cells and tissue lysates, it is important to understand the role of redox state in tissue in vivo/ex vivo and image its heterogeneity. Redox scanning is a clinically-translatable method for imaging tissue mitochondrial redox potential with a submillimeter resolution. Redox scanning data in mouse models of human cancers demonstrate a correlation between mitochondrial redox state and tumor metastatic potential. I will discuss the significance of this correlation and possible directions for future research. PMID:22895837

  5. Constraint-Based Modeling Highlights Cell Energy, Redox Status and α-Ketoglutarate Availability as Metabolic Drivers for Anthocyanin Accumulation in Grape Cells Under Nitrogen Limitation

    Directory of Open Access Journals (Sweden)

    Eric Soubeyrand

    2018-05-01

    Full Text Available Anthocyanin biosynthesis is regulated by environmental factors (such as light, temperature, and water availability and nutrient status (such as carbon, nitrogen, and phosphate nutrition. Previous reports show that low nitrogen availability strongly enhances anthocyanin accumulation in non carbon-limited plant organs or cell suspensions. It has been hypothesized that high carbon-to-nitrogen ratio would lead to an energy excess in plant cells, and that an increase in flavonoid pathway metabolic fluxes would act as an “energy escape valve,” helping plant cells to cope with energy and carbon excess. However, this hypothesis has never been tested directly. To this end, we used the grapevine Vitis vinifera L. cultivar Gamay Teinturier (syn. Gamay Freaux or Freaux Tintorier, VIVC #4382 cell suspension line as a model system to study the regulation of anthocyanin accumulation in response to nitrogen supply. The cells were sub-cultured in the presence of either control (25 mM or low (5 mM nitrate concentration. Targeted metabolomics and enzyme activity determinations were used to parametrize a constraint-based model describing both the central carbon and nitrogen metabolisms and the flavonoid (phenylpropanoid pathway connected by the energy (ATP and reducing power equivalents (NADPH and NADH cofactors. The flux analysis (2 flux maps generated, for control and low nitrogen in culture medium clearly showed that in low nitrogen-fed cells all the metabolic fluxes of central metabolism were decreased, whereas fluxes that consume energy and reducing power, were either increased (upper part of glycolysis, shikimate, and flavonoid pathway or maintained (pentose phosphate pathway. Also, fluxes of flavanone 3β-hydroxylase, flavonol synthase, and anthocyanidin synthase were strongly increased, advocating for a regulation of the flavonoid pathway by alpha-ketoglutarate levels. These results strongly support the hypothesis of anthocyanin biosynthesis acting as

  6. Antioxidant status of interval-trained athletes in various sports.

    Science.gov (United States)

    Dékány, M; Nemeskéri, V; Györe, I; Harbula, I; Malomsoki, J; Pucsok, J

    2006-02-01

    Muscular exercise results in an increased production of free radicals and other forms of reactive oxygen species (ROS). Further, developing evidence implicates cytotoxins as an underlying etiology of exercise-induced stimuli in muscle redox status, which could result in muscle fatigue and/or injury. Two major classes of endogenous protective mechanisms (enzymatic and nonenzymatic antioxidants) work together to reduce the harmful effects of oxidants in the cell. This study examined the effects of acute physical exercise on the enzymatic antioxidant systems of different athletes and comparison was made to the mechanism of action of three main antioxidant enzymes in the blood. Handball players (n = 6), water-polo players (n = 20), hockey players (n = 22), basketball players (n = 24), and a sedentary control group (n = 10 female and n = 9 male) served as the subjects of this study. The athletes were divided into two groups according to the observed changes of activity of superoxide dismutase enzyme. The antioxidant enzyme systems were characterized by catalase (CAT), glutathione-peroxidase (GPX), and superoxide-dismutase (SOD) and measured by spectrophotometry. An important finding in the present investigation is that when the activities of SOD increased, the activities of GPX and CAT increased also and this finding related to the physical status of interval-trained athletes. Positive correlation between SOD and GPX activities was observed (r = 0.38 females, r = 0.56 males; p antioxidant enzyme systems of athletes are sport specific, and different from control subjects. Presumably, with interval-trained athletes, hydrogen-peroxide is significantly eliminated by glutathione-peroxidase. From these results it can be concluded that the blood redox status should be taken into consideration when establishing a fitness level for individual athletes.

  7. 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.

  8. TEMPOL increases NAD+ and improves redox imbalance in obese mice

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. Pyridine nucleotides in regulation of cell death and survival by redox and non-redox reactions.

    Science.gov (United States)

    Novak Kujundžić, Renata; Žarković, Neven; Gall Trošelj, Koraljka

    2014-01-01

    Changes of the level and ratios of pyridine nucleotides determine metabolism- dependent cellular redox status and the activity of poly(ADP-ribose) polymerases (PARPs) and sirtuins, thereby influencing several processes closely related to cell survival and death. Pyridine nucleotides participate in numerous metabolic reactions whereby their net cellular level remains constant, but the ratios of NAD+/NADP+ and NADH/NADPH oscillate according to metabolic changes in response to diverse stress signals. In non-redox reactions, NAD+ is degraded and quickly, afterward, resynthesized in the NAD+ salvage pathway, unless overwhelming activation of PARP-1 consumes NAD+ to the point of no return, when the cell can no longer generate enough ATP to accommodate NAD+ resynthesis. The activity of PARP-1 is mandatory for the onset of cytoprotective autophagy on sublethal stress signals. It has become increasingly clear that redox status, largely influenced by the metabolism-dependent composition of the pyridine nucleotides pool, plays an important role in the synthesis of pro-apoptotic and anti-apoptotic sphingolipids. Awareness of the involvement of the prosurvival sphingolipid, sphingosine-1-phosphate, in transition from inflammation to malignant transformation has recently emerged. Here, the participation of pyridine nucleotides in redox and non-redox reactions, sphingolipid metabolism, and their role in cell fate decisions is reviewed.

  11. Redox environment in stem and differentiated cells: A quantitative approach

    Directory of Open Access Journals (Sweden)

    O.G. Lyublinskaya

    2017-08-01

    Full Text Available Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H2DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Keywords: Embryonic stem cells, Differentiated cells, ROS, Redox status, H2DCFDA, HyPer, Flow cytometry, Quantitative redox biology

  12. Glutathione, cell proliferation and differentiation | Ashtiani | African ...

    African Journals Online (AJOL)

    All organisms require an equivalent source for living. Reduced glutathione is the most abundant thiol containing protein in mammalian cells and organs. Glutathione was discovered by Hopkins in 1924 who published his findings in JBC. It is a three peptide containing glutamic acid, cystein and glycin and is found in reduced ...

  13. 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.

  14. Redox Buffer Strength

    Science.gov (United States)

    de Levie, Robert

    1999-04-01

    The proper functioning of enzymes in bodily fluids requires that the pH be maintained within rather narrow limits. The first line of defense against large pH fluctuations in such fluids is the passive control provided by the presence of pH buffers. The ability of pH buffers to stabilize the pH is indicated by the buffer value b introduced in 1922 by van Slyke. It is equally important for many enzymes that the redox potential is kept within a narrow range. In that case, stability of the potential is most readily achieved with a redox buffer. In this communication we define the redox buffer strength by analogy with acid-base buffer strength.

  15. Identification of redox-sensitive cysteines in the arabidopsis proteome using OxiTRAQ, a quantitative redox proteomics method

    KAUST Repository

    Liu, Pei

    2014-01-28

    Cellular redox status plays a key role in mediating various physiological and developmental processes often through modulating activities of redox-sensitive proteins. Various stresses trigger over-production of reactive oxygen/nitrogen species which lead to oxidative modifications of redox-sensitive proteins. Identification and characterization of redox-sensitive proteins are important steps toward understanding molecular mechanisms of stress responses. Here, we report a high-throughput quantitative proteomic approach termed OxiTRAQ for identifying proteins whose thiols undergo reversible oxidative modifications in Arabidopsis cells subjected to oxidative stress. In this approach, a biotinylated thiol-reactive reagent is used for differential labeling of reduced and oxidized thiols. The biotin-tagged peptides are affinity purified, labeled with iTRAQ reagents, and analyzed using a paralleled HCD-CID fragmentation mode in an LTQ-Orbitrap. With this approach, we identified 195 cysteine-containing peptides from 179 proteins whose thiols underwent oxidative modifications in Arabidopsis cells following the treatment with hydrogen peroxide. A majority of those redox-sensitive proteins, including several transcription factors, were not identified by previous redox proteomics studies. This approach allows identification of the specific redox-regulated cysteine residues, and offers an effective tool for elucidation of redox proteomes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Protective effect of soybeans as protein source in the diet against cadmium-aorta redox and morphological alteration

    Energy Technology Data Exchange (ETDEWEB)

    Pérez Díaz, Matías F.F.; Acosta, Mariano; Mohamed, Fabián H.; Ferramola, Mariana L.; Oliveros, Liliana B.; Gimenez, María S., E-mail: marisofigime44@gmail.com

    2013-11-01

    We investigated the effects of cadmium exposition on thoracic aorta redox status and morphology, and the putative protective effect of soybeans in the diet. Male Wistar rats were separated into 6 groups: 3 fed with a diet containing casein and 3 containing soybeans, as protein source. Within each protein group, one was given tap water (control) and the other two tap water containing 15 and 100 ppm of Cd{sup 2+}, respectively, for two months. In rats fed with casein diet, 15 ppm of Cd induced an increase of thiobarbituric acid-reactive substances (TBARS), and of the catalase (CAT) and glutathione peroxidase (GPx) activities, which were even higher with 100 ppm of Cd{sup 2+}, in aorta. Also, 100 ppm Cd{sup 2+} exposure increased superoxide dismutase (CuZnSOD) activity; CAT, GPX, SOD, Nrf2 and metallothioneine II mRNA expressions and CAT, GPx and NOX-2 protein levels, compared with control. Aorta endothelial and cytoplasmic alterations were observed. However, with the soybeans diet, 15 and 100 ppm of Cd{sup 2+} did not modify TBARS levels; CAT, GPX and Nrf2 mRNA expressions; CAT, GPx and NOX-2 protein; and the aorta morphology, compared with control. The soybean diet attenuates the redox changes and protects against morphological alterations induced, in a dose-dependent way, by Cd in aorta. - Highlights: • Under casein diet, 100 ppm Cd{sup 2+} in drinking water induces oxidative stress in aorta. • Under casein diet, 100 ppm Cd{sup 2+} increases Nrf2, MT II and NOX2 expressions in aorta. • Under casein diet, 100 ppm Cd{sup 2+} induces morphological changes in rat aorta. • The soybean diet attenuates the redox changes induced by Cd in rat aorta. • The soybean diet attenuates morphological alterations induced by Cd in rat aorta.

  17. Protective effect of soybeans as protein source in the diet against cadmium-aorta redox and morphological alteration

    International Nuclear Information System (INIS)

    Pérez Díaz, Matías F.F.; Acosta, Mariano; Mohamed, Fabián H.; Ferramola, Mariana L.; Oliveros, Liliana B.; Gimenez, María S.

    2013-01-01

    We investigated the effects of cadmium exposition on thoracic aorta redox status and morphology, and the putative protective effect of soybeans in the diet. Male Wistar rats were separated into 6 groups: 3 fed with a diet containing casein and 3 containing soybeans, as protein source. Within each protein group, one was given tap water (control) and the other two tap water containing 15 and 100 ppm of Cd 2+ , respectively, for two months. In rats fed with casein diet, 15 ppm of Cd induced an increase of thiobarbituric acid-reactive substances (TBARS), and of the catalase (CAT) and glutathione peroxidase (GPx) activities, which were even higher with 100 ppm of Cd 2+ , in aorta. Also, 100 ppm Cd 2+ exposure increased superoxide dismutase (CuZnSOD) activity; CAT, GPX, SOD, Nrf2 and metallothioneine II mRNA expressions and CAT, GPx and NOX-2 protein levels, compared with control. Aorta endothelial and cytoplasmic alterations were observed. However, with the soybeans diet, 15 and 100 ppm of Cd 2+ did not modify TBARS levels; CAT, GPX and Nrf2 mRNA expressions; CAT, GPx and NOX-2 protein; and the aorta morphology, compared with control. The soybean diet attenuates the redox changes and protects against morphological alterations induced, in a dose-dependent way, by Cd in aorta. - Highlights: • Under casein diet, 100 ppm Cd 2+ in drinking water induces oxidative stress in aorta. • Under casein diet, 100 ppm Cd 2+ increases Nrf2, MT II and NOX2 expressions in aorta. • Under casein diet, 100 ppm Cd 2+ induces morphological changes in rat aorta. • The soybean diet attenuates the redox changes induced by Cd in rat aorta. • The soybean diet attenuates morphological alterations induced by Cd in rat aorta

  18. Simultaneous anionic and cationic redox

    Science.gov (United States)

    Jung, Sung-Kyun; Kang, Kisuk

    2017-12-01

    It is challenging to unlock anionic redox activity, accompanied by full utilization of available cationic redox process, to boost capacity of battery cathodes. Now, material design by tuning the metal-oxygen interaction is shown to be a promising solution.

  19. 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

  20. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    Science.gov (United States)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, Pbalneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG 150 mg/dl), the value decreased ( Pbalneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  1. Modulation of redox regulatory molecules and electron transport chain activity in muscle of air breathing fish Heteropneustes fossilis under air exposure stress.

    Science.gov (United States)

    Paital, Biswaranjan

    2014-01-01

    Responses of redox regulatory system to long-term survival (>18 h) of the catfish Heteropneustes fossilis in air are not yet understood. Lipid and protein oxidation level, oxidant (H2O2) generation, antioxidative status (levels of superoxide dismutase, catalase, glutathione peroxidase and reductase, ascorbic acid and non-protein sulfhydryl) and activities of respiratory complexes (I, II, III and IV) in mitochondria were investigated in muscle of H. fossilis under air exposure condition (0, 3, 6, 12 and 18 h at 25 °C). The increased levels of both H2O2 and tissue oxidation were observed due to the decreased activities of antioxidant enzymes in muscle under water deprivation condition. However, ascorbic acid and non-protein thiol groups were the highest at 18 h air exposure time. A linear increase in complex II activity with air exposure time and an increase up to 12 h followed by a decrease in activity of complex I at 18 h were observed. Negative correlation was observed for complex III and V activity with exposure time. Critical time to modulate the above parameters was found to be 3 h air exposure. Dehydration induced oxidative stress due to modulation of electron transport chain and redox metabolizing enzymes in muscle of H. fossilis was clearly observed. Possible contribution of redox regulatory system in muscle tissue of the fish for long-term survival in air is elucidated. Results of the present study may be useful to understand the redox metabolism in muscle of fishes those are exposed to air in general and air breathing fishes in particular.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. Glutathione turnover in 14 rat tissues

    International Nuclear Information System (INIS)

    Potter, D.W.; Tran, T.

    1990-01-01

    GSH is a tripeptide found in all tissues and is important in maintaining cellular redox status. First-order rate constants for GSH turnover were determined for various tissues of Fischer male rats. Animals were administered [ 35 S]Cys by tail vein injection and GSH turnover was estimated by the decrease in GSH specific activity following incorporation of Cys, 1-102 hr after administration. Tissue nonprotein sulfhydryls (NPSH) were detected by Ellman's assay and compared with GSH and Cys concentrations determined by HPLC with electrochemical detection. [ 35 S]GSH was analyzed by HPLC equipped with a flow-through radioactivity detector. Although total GSH and Cys were usually slightly lower than NPSH concentrations for the tissues examined, both assay systems gave comparable results. An exception was the glandular stomach which had approximately 2-fold higher NPSH. Liver and kidney had rapid turnover rates with GSH half-lives between 2-5 hr, while heart and skeletal muscle tissue had half-lives of 80-90 hr. Turnover in the blood was slowest, with a half-life of 170 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach > duodenum = small intestine = caecum = large intestine = colon > forestomach. GSH half-life in lung and skin was approximately 45 hr. These studies indicate that tissues utilize GSH at markedly different rates

  6. Redox Flow Batteries, a Review

    Energy Technology Data Exchange (ETDEWEB)

    Knoxville, U. Tennessee; U. Texas Austin; U, McGill; Weber, Adam Z.; Mench, Matthew M.; Meyers, Jeremy P.; Ross, Philip N.; Gostick, Jeffrey T.; Liu, Qinghua

    2011-07-15

    Redox flow batteries are enjoying a renaissance due to their ability to store large amounts of electrical energy relatively cheaply and efficiently. In this review, we examine the components of redox flow batteries with a focus on understanding the underlying physical processes. The various transport and kinetic phenomena are discussed along with the most common redox couples.

  7. Redox Modulations, Antioxidants, and Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Erik A. Fraunberger

    2016-01-01

    Full Text Available Although antioxidants, redox modulations, and neuropsychiatric disorders have been widely studied for many years, the field would benefit from an integrative and corroborative review. Our primary objective is to delineate the biological significance of compounds that modulate our redox status (i.e., reactive species and antioxidants as well as outline their current role in brain health and the impact of redox modulations on the severity of illnesses. Therefore, this review will not enter into the debate regarding the perceived medical legitimacy of antioxidants but rather seek to clarify their abilities and limitations. With this in mind, antioxidants may be interpreted as natural products with significant pharmacological actions in the body. A renewed understanding of these often overlooked compounds will allow us to critically appraise the current literature and provide an informed, novel perspective on an important healthcare issue. In this review, we will introduce the complex topics of redox modulations and their role in the development of select neuropsychiatric disorders.

  8. Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice.

    Science.gov (United States)

    Niemiec, T; Sikorska, J; Harrison, A; Szmidt, M; Sawosz, E; Wirth-Dzieciolowska, E; Wilczak, J; Pierzynowski, S

    2011-02-01

    The objective of this study was to evaluate the effect of α-ketoglutarate on redox state parameters and arterial elasticity in elderly mice. Mice in the control group were fed with standard diet, while the experimental animals received the diet supplemented either with calcium (Ca-AKG) or sodium salt of α-ketoglutarate (Na-AKG). The experimental animals were divided into 4 groups with 10 individuals in each: control I (12 months old), control II (2 months old), experimental group I fed with Ca-AKG (12 months old) and experimental group II fed with Na-AKG (12 months old). Mice treated with Ca-AKG as well as the control II animals demonstrated significantly higher level of total antioxidant status (TAS), comparing to the control I animals and those treated with Ca-AKG. Thiobarbituric acid reactive substances (TBARS) level in blood plasma was found significantly lower in young and Ca-AKG treated mice. TBARS liver concentration was significantly different in each examined group. The study also demonstrates the decrease in TBARS level in Ca-AKG treated animals. Treatment with Na-AKG significantly increased glutathione peroxidase activity and decreased the activity of superoxide dismutase. The presented results suggest that Ca-AKG protects the organism against the free radicals related elderly processes. The study presents also the effect of Ca-AKG treatment on arterial elastic characteristics in elderly mice. The beneficial effect of Ca-AKG on ageing organisms was confirmed via redox state stabilization and blood vessel elasticity improvement.

  9. 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.

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

    DEFF Research Database (Denmark)

    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...

  11. Perturbations in carotenoid and porphyrin status result in differential photooxidative stress signaling and antioxidant responses.

    Science.gov (United States)

    Park, Joon-Heum; Jung, Sunyo

    2018-02-12

    We examined differential photooxidative stress signaling and antioxidant responses in rice plants treated with norflurazon (NF) and oxyfluorfen (OF), which are inhibitors of carotenoid and porphyrin biosynthesis, respectively. Plants treated with OF markedly increased levels of cellular leakage and malondialdehyde, compared with NF-treated plants, showing that OF plants suffered greater oxidative damage with respect to membrane integrity. The enhanced production of H 2 O 2 in response to OF, but not NF, indicates the important role of H 2 O 2 in activation of photooxidative stress signaling in OF plants. In response to NF and OF, the increased levels of free salicylic acid as well as maintenance of the redox ratio of ascorbate and glutathione pools to a certain level are considered to be crucial factors in the protection against photooxidation. Plants treated with OF greatly up-regulated catalase (CAT) activity and Cat transcript levels, compared with NF-treated plants. Interestingly, NF plants showed no noticeable increase in oxidative metabolism, although they did show considerable increases in ascorbate peroxidase (APX) and peroxidase activities and transcript levels of APX, as in OF plants. Our results suggest that perturbations in carotenoid and porphyrin status by NF and OF can be sensed by differential photooxidative stress signaling, such as that involving H 2 O 2 , redox state of ascorbate and glutathione, and salicylic acid, which may be responsible for at least part of the induction of ROS-scavenging enzymes. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. 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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. High salinity helps the halophyte Sesuvium portulacastrum in defense against Cd toxicity by maintaining redox balance and photosynthesis.

    Science.gov (United States)

    Wali, Mariem; Gunsè, Benet; Llugany, Mercè; Corrales, Isabel; Abdelly, Chedly; Poschenrieder, Charlotte; Ghnaya, Tahar

    2016-08-01

    NaCl alleviates Cd toxicity in Sesvium portulacastrum by maintaining plant water status and redox balance, protecting chloroplasts structure and inducing some potential Cd (2+) chelators as GSH and proline. It has been demonstrated that NaCl alleviates Cd-induced growth inhibition in the halophyte Sesuvium portulacastrum. However, the processes that mediate this effect are still unclear. In this work we combined physiological, biochemical and ultrastructural studies to highlight the effects of salt on the redox balance and photosynthesis in Cd-stressed plants. Seedlings were exposed to different Cd concentrations (0, 25 and 50 µM Cd) combined with low (0.09 mM) (LS), or high (200 mM) NaCl (HS) in hydroponic culture. Plant-water relations, photosynthesis rate, leaf gas exchange, chlorophyll fluorescence, chloroplast ultrastructure, and proline and glutathione concentrations were analyzed after 1 month of treatment. In addition, the endogenous levels of stress-related hormones were determined in plants subjected to 25 µM Cd combined with both NaCl concentrations. In plants with low salt supply (LS), Cd reduced growth, induced plant dehydration, disrupted chloroplast structure and functioning, decreased net CO2 assimilation rate (A) and transpiration rate (E), inhibited the maximum potential quantum efficiency (Fv/Fm) and the quantum yield efficiency (Φ PSII) of PSII, and enhanced the non-photochemical quenching (NPQ). The addition of 200 mM NaCl (HS) to the Cd-containing medium culture significantly mitigated Cd phytotoxicity. Hence, even at similar internal Cd concentrations, HS-Cd plants were less affected by Cd than LS-Cd ones. Hence, 200 mM NaCl significantly alleviates Cd-induced toxicity symptoms, growth inhibition, and photosynthesis disturbances. The cell ultrastructure was better preserved in HS-Cd plants but affected in LS-Cd plants. The HS-Cd plants showed also higher concentrations of reduced glutathione (GSH), proline and jasmonic acid (JA

  16. Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.

    Science.gov (United States)

    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.

  17. Glutathione Metabolism and Parkinson’s Disease

    OpenAIRE

    Smeyne, Michelle; Smeyne, Richard Jay

    2013-01-01

    It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how...

  18. Auranofin-induced oxidative stress causes redistribution of the glutathione pool in Taenia crassiceps cysticerci.

    Science.gov (United States)

    Martínez-González, J J; Guevara-Flores, A; Rendón, J L; Arenal, I P Del

    2015-05-01

    Previously, we have studied the effect of the gold-compound auranofin (AF) on both thioredoxin-glutathione reductasa (TGR) activity and viability of Taenia crassiceps cysticerci. It was demonstrated that micromolar concentrations of AF were high enough to fully inhibit TGR and kill the parasites. In this work, the dynamics of changes in the glutathione pool of T. crassiceps cysticerci following the addition of AF, was analyzed. A dose-dependent decrease in the internal glutathione concentration, concomitant with an increase in ROS production was observed. These changes were simultaneous with the formation of glutathione-protein complexes and the export of glutathione disulfide (GSSG) to the culture medium. Incubation of cysticerci in the presence of both AF and N-acetyl cysteine (NAC) prevents all the above changes, maintaining cysticerci viability. By contrast, the presence of both AF and buthionine sulfoximine (BSO) resulted in a potentiation of the effects of the gold compound, jeopardizing cysticerci viability. These results suggest the lethal effect of AF on T. crassiceps cysticerci, observed at micromolar concentrations, can be explained as a consequence of major changes in the glutathione status, which results in a significant increase in the oxidative stress of the parasites. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. 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.

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

    Science.gov (United States)

    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.

  1. 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.

  2. 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.

  3. Aqueous liquid redox desulfurisation

    Energy Technology Data Exchange (ETDEWEB)

    Reicher, M.; Niemiec, B.; Katona, T.

    1999-12-01

    The LO-CAT II process is an aqueous liquid redox process which uses ferric and ferrous iron catalysts to oxidise hydrogen sulfide (from sour gas) to elemental sulfur: the relevant chemical equations are given. Chelating agents keep the iron in solution. The system is described under the headings of (i) LO-CAT chemistry, (ii) design parameters, (iii) startup challenges, (iv) present situation and (v) anticipated future conditions. Further improvements to the system are anticipated.

  4. Ediacaran Redox Fluctuations

    Science.gov (United States)

    Sahoo, S. K.; Jiang, G.; Planavsky, N. J.; Kendall, B.; Owens, J. D.; Anbar, A. D.; Lyons, T. W.

    2013-12-01

    Evidence for pervasive oxic conditions, and likely even deep ocean oxygenation has been documented at three intervals in the lower (ca. 632 Ma), middle (ca. 580 Ma) and upper (ca. 551 Ma) Ediacaran. The Doushantuo Formation in South China hosts large enrichments of redox-sensitive trace element (e.g., molybdenum, vanadium and uranium) in anoxic shales, which are indicative of a globally oxic ocean-atmosphere system. However, ocean redox conditions between these periods continue to be a topic of debate and remain elusive. We have found evidence for widespread anoxic conditions through much of the Ediacaran in the deep-water Wuhe section in South China. During most of the Ediacaran-early Cambrian in basinal sections is characterized by Fe speciation data and pyrite morphologies that indicate deposition under euxinic conditions with near-crustal enrichments of redox-sensitive element and positive pyrite-sulfur isotope values, which suggest low levels of marine sulfate and widespread euxinia. Our work reinforces an emerging view that the early Earth, including the Ediacaran, underwent numerous rises and falls in surface oxidation state, rather than a unidirectional rise as originally imagined. The Ediacaran ocean thus experienced repetitive expansion and contraction of marine chalcophilic trace-metal levels that may have had fundamental impact on the slow evolution of early animals and ecosystems. Further, this framework forces us to re-examine the relationship between Neoproterozoic oxygenation and metazoan diversification. Varying redox conditions through the Cryogenian and Ediacaran may help explain molecular clock and biomarker evidence for an early appearance and initial diversification of metazoans but with a delay in the appearance of most major metazoan crown groups until close to Ediacaran-Cambrian boundary.

  5. Supramolecular interactions of oxidative stress biomarker glutathione with fluorone black

    Science.gov (United States)

    Hepel, Maria; Stobiecka, Magdalena

    2018-03-01

    Oxidative stress biomarkers, including glutathione (GSH) and related compounds, are involved in a variety of interactions enabling redox potential maintenance in living cells and protection against radicals. Since the oxidative stress is promoting and, in many cases, inducing serious illnesses, monitoring of GSH levels can aid in diagnostics and disease prevention. Herein, we report on the discovery of the formation of a supramolecular ensemble of GSH with fluorone black (9-phenyl fluorone, FB) which is optically active and enables sensitive determination of GSH by resonance elastic light scattering (RELS). We have found that supramolecular interactions of GSH with FB can be probed with spectroscopic, RELS, and electrochemical methods. Our investigations show that RELS intensity for FB solutions increases with GSH concentration while fluorescence emission of FB is not affected, as quenching begins only above 0.8 mM GSH. The UV-Vis difference spectra show a positive peak at 383 nm and a negative peak at 458 nm, indicating a higher-energy absorbing complex in comparison to the non-bonded FB host. Supramolecular interactions of FB with GSH have also been corroborated by electrochemical measurements involving two configurations of FB-GSH ensembles on electrodes: (i) an inverted orientation on Au-coated quartz crystal piezoelectrode (Au@SG-FB), with strong thiolate bonding to gold, and (ii) a non-inverted orientation on glassy carbon electrode (GCE@FB-GS), with weak π-π stacking attachment and efficient charge mediation through the ensemble. The formation of a supramolecular ensemble with hydrogen bonding has also been confirmed by quantum mechanical calculations. The discovery of supramolecular FB-GSH ensemble formation enables elucidating the mechanisms of strong RELS responses, changes in UV-Vis absorption spectra, and the electrochemical reactivity. Also, it provides new insights to the understanding of the efficient charge-transfer in redox potential homeostasis

  6. L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential.

    Science.gov (United States)

    Kumar, Prabhanshu; Maurya, Pawan Kumar

    2013-06-01

    Thiol compounds such as cysteine (Cys) and reduced glutathione (GSH) play an important role in human aging and age-related diseases. In erythrocytes, GSH is synthesized by glutamic acid, cysteine, and glycine, but the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate several parameters that are known to degenerate during human aging. We have studied L-cysteine efflux in vitro in human erythrocytes as a function of age by suspending cells in solution containing 10 mM L-cysteine for uptake; later cells were re-suspended in phosphate-buffered saline (PBS)-glucose to allow efflux. Change in the free sulfhydryl (-SH) concentration was then measured to calculate the rate of efflux. The GSH/oxidized glutathione (GSSG) ratio was taken as a control to study the oxidation/reduction state of the erythrocyte. The total anti-oxidant potential of plasma was measured in terms of ferric reducing ability of plasma (FRAP) values. We have shown a significant (pL-cysteine in erythrocytes during human aging, and the GSH/GSSG ratio decreases as a function of human age. The decline in L-cysteine efflux during aging correlates with the decrease in GSH and the FRAP value. This finding may help to explain the shift in the redox status and low GSH concentration that might determine the rate of L-cysteine efflux observed in erythrocytes and an important factor in the development of oxidative stress in erythrocytes during aging.

  7. Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review

    Science.gov (United States)

    Kaltsatou, Antonia; Jamurtas, Athanasios Z.; Koutedakis, Yiannis; Stefanidis, Ioannis; Sakkas, Giorgos K.

    2016-01-01

    Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD. PMID:27563376

  8. Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Konstantina P. Poulianiti

    2016-01-01

    Full Text Available Patients with chronic kidney disease (CKD experience imbalance between oxygen reactive species (ROS production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD.

  9. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  12. The glutathione cycle: Glutathione metabolism beyond the γ-glutamyl cycle.

    Science.gov (United States)

    Bachhawat, Anand Kumar; Yadav, Shambhu

    2018-04-17

    Glutathione was discovered in 1888, over 125 years ago. Since then, our understanding of various functions and metabolism of this important molecule has grown over these years. But it is only now, in the last decade, that a somewhat complete picture of its metabolism has emerged. Glutathione metabolism has till now been largely depicted and understood by the γ-glutamyl cycle that was proposed in 1970. However, new findings and knowledge particularly on the transport and degradation of glutathione have revealed that many aspects of the γ-glutamyl cycle are incorrect. Despite this, an integrated critical analysis of the cycle has never been undertaken and this has led to the cycle and its errors perpetuating in the literature. This review takes a careful look at the γ-glutamyl cycle and its shortcomings and presents a "glutathione cycle" that captures the current understanding of glutathione metabolism. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  13. 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.

  14. Redox electrode materials for supercapatteries

    OpenAIRE

    Yu, Linpo; Chen, George Z.

    2016-01-01

    Redox electrode materials, including transition metal oxides and electronically conducting polymers, are capable of faradaic charge transfer reactions, and play important roles in most electrochemical energy storage devices, such as supercapacitor, battery and supercapattery. Batteries are often based on redox materials with low power capability and safety concerns in some cases. Supercapacitors, particularly those based on redox inactive materials, e.g. activated carbon, can offer high power...

  15. 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...

  16. 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.

  17. Role of glutathione in immunity and inflammation in the lung

    Directory of Open Access Journals (Sweden)

    Pietro Ghezzi

    2011-01-01

    Full Text Available Pietro GhezziBrighton and Sussex Medical School, Trafford Centre, Falmer, Brighton, UKAbstract: Reactive oxygen species and thiol antioxidants, including glutathione (GSH, regulate innate immunity at various levels. This review outlines the redox-sensitive steps of the cellular mechanisms implicated in inflammation and host defense against infection, and describes how GSH is not only important as an antioxidant but also as a signaling molecule. There is an extensive literature of the role of GSH in immunity. Most reviews are biased by an oversimplified picture where “bad” free radicals cause all sorts of diseases and “good” antioxidants protect from them and prevent oxidative stress. While this may be the case in certain fields (eg, toxicology, the role of thiols (the topic of this review in immunity certainly requires wearing scientist’s goggles and being prepared to accept a more complex picture. This review aims at describing the role of GSH in the lung in the context of immunity and inflammation. The first part summarizes the history and basic concepts of this picture. The second part focuses on GSH metabolism/levels in pathology, the third on the role of GSH in innate immunity and inflammation, and the fourth gives 4 examples describing the importance of GSH in the response to infections.Keywords: antioxidants, oxidative stress, sepsis, infection, cysteine

  18. Role of glutathione biosynthesis in endothelial dysfunction and fibrosis.

    Science.gov (United States)

    Espinosa-Díez, Cristina; Miguel, Verónica; Vallejo, Susana; Sánchez, Francisco J; Sandoval, Elena; Blanco, Eva; Cannata, Pablo; Peiró, Concepción; Sánchez-Ferrer, Carlos F; Lamas, Santiago

    2018-04-01

    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 BH 4 . 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. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Role of glutathione transport processes in kidney function

    International Nuclear Information System (INIS)

    Lash, Lawrence H.

    2005-01-01

    The kidneys are highly dependent on an adequate supply of glutathione (GSH) to maintain normal function. This is due, in part, to high rates of aerobic metabolism, particularly in the proximal tubules. Additionally, the kidneys are potentially exposed to high concentrations of oxidants and reactive electrophiles. Renal cellular concentrations of GSH are maintained by both intracellular synthesis and transport from outside the cell. Although function of specific carriers has not been definitively demonstrated, it is likely that multiple carriers are responsible for plasma membrane transport of GSH. Data suggest that the organic anion transporters OAT1 and OAT3 and the sodium-dicarboxylate 2 exchanger (SDCT2 or NaDC3) mediate uptake across the basolateral plasma membrane (BLM) and that the organic anion transporting polypeptide OATP1 and at least one of the multidrug resistance proteins mediate efflux across the brush-border plasma membrane (BBM). BLM transport may be used pharmacologically to provide renal proximal tubular cells with exogenous GSH to protect against oxidative stress whereas BBM transport functions physiologically in turnover of cellular GSH. The mitochondrial GSH pool is derived from cytoplasmic GSH by transport into the mitochondrial matrix and is mediated by the dicarboxylate and 2-oxoglutarate exchangers. Maintenance of the mitochondrial GSH pool is critical for cellular and mitochondrial redox homeostasis and is important in determining susceptibility to chemically induced apoptosis. Hence, membrane transport processes are critical to regulation of renal cellular and subcellular GSH pools and are determinants of susceptibility to cytotoxicity induced by oxidants and electrophiles

  20. 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

  1. Concomitant ingestion of lactic acid bacteria and black tea synergistically enhances flavonoid bioavailability and attenuates d-galactose-induced oxidative stress in mice via modulating glutathione antioxidant system.

    Science.gov (United States)

    Zhao, Danyue; Shah, Nagendra P

    2016-12-01

    Black tea (BT) has been positively linked to improved redox status, while its efficacy is limited due to the low bioavailability of BT flavonoids. In addition to the direct antioxidant activity, flavonoids regulate redox balance via inducing endogenous antioxidants, particularly glutathione (GSH) and GSH-dependent antioxidant enzymes. This work first examined the effect of lactic acid bacteria (LAB) and BT alone or in combination on flavonoid bioavailability and metabolism; next, the effect of LAB-fermented BT diet in attenuating oxidative stress in mice and the underlying mechanisms were studied. Phenolic profiles of plasma, urine and feces from healthy mice consuming plain yogurt, BT milk (BTM) or BT yogurt (BTY) were acquired using LC-MS/MS. Plasma antioxidant capacity, lipid peroxidation level, content of nonprotein thiols and expression of GSH-related antioxidant enzymes and Nrf2 were examined in d-galactose-treated mice. Total flavonoid content in plasma following a single dose of BTY attained 0.657 μmol/l, increased by 50% compared with the BTM group. Increased excretion of phenolic metabolite and hippuric acid in urine and feces indicated enhanced metabolism of flavonoids in BTY-fed mice. In the second study, 8-week concomitant LAB-BT treatment of oxidatively stressed mice effectively restored plasma antioxidant capacity and GSH levels, and mitigated lipid peroxidation, which were associated with significant induction of GSH-dependent antioxidant enzymes and nuclear accumulation of Nrf2. Our results demonstrated the effect of LAB fermentation in enhancing BT flavonoid bioavailability in vivo. The synergistic antioxidant efficacy of LAB-BT diet implied its therapeutic potential in enhancing antioxidant defenses and protecting organisms from oxidative damage. Copyright © 2016. Published by Elsevier Inc.

  2. 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.

  3. Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass

    Directory of Open Access Journals (Sweden)

    Tatiana G. Polotow

    2015-09-01

    Full Text Available Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs and the antioxidant carotenoid astaxanthin (ASTA. However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation, drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

  4. Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass.

    Science.gov (United States)

    Polotow, Tatiana G; Poppe, Sandra C; Vardaris, Cristina V; Ganini, Douglas; Guariroba, Maísa; Mattei, Rita; Hatanaka, Elaine; Martins, Maria F; Bondan, Eduardo F; Barros, Marcelo P

    2015-09-28

    Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

  5. Enhanced erythrocyte antioxidant status following an 8-week aerobic exercise training program in heavy drinkers.

    Science.gov (United States)

    Georgakouli, Kalliopi; Manthou, Eirini; Fatouros, Ioannis G; Georgoulias, Panagiotis; Deli, Chariklia K; Koutedakis, Yiannis; Theodorakis, Yannis; Jamurtas, Athanasios Z

    2018-06-01

    Alcohol-induced oxidative stress is involved in the development and progression of various pathological conditions and diseases. On the other hand, exercise training has been shown to improve redox status, thus attenuating oxidative stress-associated disease processes. The purpose of the present study was to evaluate the effect of an exercise training program that has been previously reported to decrease alcohol consumption on blood redox status in heavy drinkers. In a non-randomized within-subject design, 11 sedentary, heavily drinking men (age: 30.3 ± 3.5 years; BMI: 28.4 ± 0.86 kg/m 2 ) participated first in a control condition for 4 weeks, and then in an intervention where they completed an 8-week supervised aerobic training program of moderate intensity (50-60% of the heart rate reserve). Blood samples were collected in the control condition (pre-, post-control) as well as before, during (week 4 of the training program), and after intervention (week 8 of the training program). Samples were analyzed for total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), uric acid (UA), bilirubin, reduced glutathione (GSH), and catalase activity. No significant change in indices of redox status in the pre- and post-control was observed. Catalase activity increased (p program enhanced erythrocyte antioxidant status in heavy drinkers, indicating that aerobic training may attenuate pathological processes caused by alcohol-induced oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Redox Modulation by Amaranth Oil in Human Lung Fibroblasts

    NARCIS (Netherlands)

    Semen, K.O.; den Hartog, G.J.M.; Kaminsky, D.V.; Sirota, T.V.; Maij, N.G.A.A.; Yelisyeyeva, O.P.; Bast, A.

    2013-01-01

    Amaranth oil has several health benefits. It has lipid lowering, anti-diabetic, immune modulatory and cytoprotective properties, activates the function of mitochondria and improves heart rate variability. It has been suggested that the effect of amaranth oil on redox status is involved in this

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. [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.

  11. ANTIOXIDANT STATUS IN DIABETIC NEUROPATHY

    Directory of Open Access Journals (Sweden)

    Giriraja Vrushabaiah Kanakapura

    2017-09-01

    Full Text Available BACKGROUND Diabetic neuropathy, retinopathy and nephropathy are the chronic complications of diabetes mellitus. Neuropathy, retinopathy and nephropathy are microvascular complication of diabetes mellitus. Antioxidant status is reduced in DM-induced retinopathy and nephropathy. Present study is undertaken to evaluate the degree of oxidative stress in diabetic neuropathy patients. The aim of the study is to study on oxidative stress as measured by lipid peroxidation marker, malondialdehyde and antienzyme status in type II DM patients with neuropathy and compared them with a controlled nondiabetic group. MATERIALS AND METHODS The study included 100 subjects from Sapthagiri Medical College, Bangalore, from January 1, 2015, to December 31, 2015, of age group 50 to 70 yrs. out of which 50 patients were non-insulin-dependent DM with neuropathy and rest 50 age and sex matched apparently healthy individuals (control group. Antioxidant status was assessed by measuring superoxide dismutase (SOD, glutathione peroxidase (GPx, glutathione reductase (GR, Catalase and Reduced Glutathione (GSH. RESULTS It showed a significant increase p<0.001 in FBS, PPBS, TC, TG, LDL, VLDL, CAT, MDA, while HDL, GSH, GPX, GR and SOD were found to be decreased significantly (p 0.001. CONCLUSION MDA was significantly elevated in diabetic group, whereas antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly decreased, which might be helpful in risk assessment of various complications of DM. The data suggests that alteration in antioxidant status and MDA may help to predict the risk of diabetic neuropathy.

  12. Effects of mercury and selenium on glutathione metabolism and oxidative stress in mallard ducks

    Science.gov (United States)

    Hoffman, D.J.; Heinz, G.H.

    1998-01-01

    Earlier studies reported on the toxicity and related oxidative stress of different forms of Se, including seleno-D,L-methionine, in mallards (Anas platyrhynchos). This study compares the effects of Se (seleno-D,L-methionine) and Hg (methylmercury chloride) separately and in combination. Mallard drakes received one of the following diets: untreated feed (controls), or feed containing 10 ppm Se, 10 ppm Hg, or 10 ppm Se in combination with 10 ppm Hg. After 10 weeks, blood, liver, and brain samples were collected for biochemical assays. The following clinical and biochemical alterations occurred in response to mercury exposure: hematocrit and hemoglobin concentrations decreased; activities of the enzymes glutathione (GSH) peroxidase (plasma and liver), glutathione-S-transferase (liver), and glucose-6-phosphate dehydrogenase (G-6-PDH) (liver and brain) decreased; hepatic oxidized glutathione (GSSG) concentration increased relative to reduced glutathione (GSH); and lipid peroxidation in the brain was evident as detected by increased thiobarbituric reactive substances (TBARS). Effects of Se alone included increased hepatic GSSG reductase activity and brain TBARS concentration. Se in combination with Hg partially or totally alleviated effects of Hg on GSH peroxidase, G-6-PDH, and GSSG. These findings are compared in relation to field observations for diving ducks and other aquatic birds. It is concluded that since both Hg and excess Se can affect thiol status, measurement of associated enzymes in conjunction with thiol status may be a useful bioindicator to discriminate between Hg and Se effects. The ability of Se to restore the activities of G-6-PDH, GSH peroxidase, and glutathione status involved in antioxidative defense mechanisms may be crucial to biological protection from the toxic effects of methyl mercury.

  13. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Redox environment in stem and differentiated cells: A quantitative approach.

    Science.gov (United States)

    Lyublinskaya, O G; Ivanova, Ju S; Pugovkina, N A; Kozhukharova, I V; Kovaleva, Z V; Shatrova, A N; Aksenov, N D; Zenin, V V; Kaulin, Yu A; Gamaley, I A; Nikolsky, N N

    2017-08-01

    Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H 2 DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Effect of Vitamin C on Glutathione Peroxidase Activities in Pregnant ...

    African Journals Online (AJOL)

    Glutathione peroxidase is one of the most important antioxidant enzymes in humans. We studied the relationship between serum glutathione peroxidase activity and vitamin C ingestion during normal pregnancy in women attending antenatal clinic in the University of Ilorin Teaching Hospital, Ilorin. Glutathione peroxidase ...

  18. Inflammatory and redox reactions in colorectal carcinogenesis.

    Science.gov (United States)

    Guina, Tina; Biasi, Fiorella; Calfapietra, Simone; Nano, Mario; Poli, Giuseppe

    2015-03-01

    It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment. © 2015 New York Academy of Sciences.

  19. 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.

  20. 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.

  1. Serum oxidant and antioxidant status in adolescents undergoing professional endurance sports training.

    Science.gov (United States)

    Tong, Tom K; Lin, Hua; Lippi, Giuseppe; Nie, Jinlei; Tian, Ye

    2012-01-01

    This study evaluated the impact of professional training on serum oxidant and antioxidant status in adolescent endurance athletes and compared it with that of untrained individuals. Firstly, serum thiobarbituric-acid-reactive substances (TBARSs), xanthine oxidase (XO), catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) were measured in 67 male runners, cyclists, and untrained adolescents. Seven-day dietary intakes were also assessed. Secondly, for age- and Tanner-stage-matched comparison, 36 out of the 67 subjects (12 for each group) were then selected and investigated. In cyclists, XO, GSH, and CAT were higher as compared with runners and controls. The CAT in runners, but not GSH and XO, was also higher than in controls. TBARS, T-AOC, and SOD did not differ among the study populations. Regarding the inter-individual relationships among serum redox statuses and dietary nutrient intakes, significant correlations were noted in CAT versus carbohydrates, protein, magnesium, and manganese; GSH versus carbohydrates, protein, fat, selenium, zinc, iron, and magnesium; XO versus cholesterol; CAT versus GSH. These findings suggest that the resting blood redox balance in the professional adolescent athletes was well maintained partly by the increase of individual antioxidant in adaptation to chronic exercise.

  2. 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

  3. Supramolecular interactions of oxidative stress biomarker glutathione with fluorone black.

    Science.gov (United States)

    Hepel, Maria; Stobiecka, Magdalena

    2018-03-05

    Oxidative stress biomarkers, including glutathione (GSH) and related compounds, are involved in a variety of interactions enabling redox potential maintenance in living cells and protection against radicals. Since the oxidative stress is promoting and, in many cases, inducing serious illnesses, monitoring of GSH levels can aid in diagnostics and disease prevention. Herein, we report on the discovery of the formation of a supramolecular ensemble of GSH with fluorone black (9-phenyl fluorone, FB) which is optically active and enables sensitive determination of GSH by resonance elastic light scattering (RELS). We have found that supramolecular interactions of GSH with FB can be probed with spectroscopic, RELS, and electrochemical methods. Our investigations show that RELS intensity for FB solutions increases with GSH concentration while fluorescence emission of FB is not affected, as quenching begins only above 0.8mM GSH. The UV-Vis difference spectra show a positive peak at 383nm and a negative peak at 458nm, indicating a higher-energy absorbing complex in comparison to the non-bonded FB host. Supramolecular interactions of FB with GSH have also been corroborated by electrochemical measurements involving two configurations of FB-GSH ensembles on electrodes: (i) an inverted orientation on Au-coated quartz crystal piezoelectrode (Au@SG-FB), with strong thiolate bonding to gold, and (ii) a non-inverted orientation on glassy carbon electrode (GCE@FB-GS), with weak π-π stacking attachment and efficient charge mediation through the ensemble. The formation of a supramolecular ensemble with hydrogen bonding has also been confirmed by quantum mechanical calculations. The discovery of supramolecular FB-GSH ensemble formation enables elucidating the mechanisms of strong RELS responses, changes in UV-Vis absorption spectra, and the electrochemical reactivity. Also, it provides new insights to the understanding of the efficient charge-transfer in redox potential homeostasis

  4. Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine

    Directory of Open Access Journals (Sweden)

    Tiziana Parasassi

    2010-01-01

    Full Text Available The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

  5. 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.

  6. The influence of heroin abuse on glutathione-dependent enzymes in human brain.

    Science.gov (United States)

    Gutowicz, Marzena; Kaźmierczak, Beata; Barańczyk-Kuźma, Anna

    2011-01-01

    Heroin is an illicit narcotic abused by millions of people worldwide. In our earlier studies we have shown that heroin intoxication changes the antioxidant status in human brain. In the present work we continued our studies by estimating the effect of heroin abuse on reduced glutathione (GSH) and enzymes related to this cofactor, such as glutathione S-transferase detoxifying electrophilics (GST) and organic peroxides (as Se-independent glutathione peroxidase-GSHPx), and Se-dependent glutathione peroxidase (Se-GSHPx) specific mainly for hydrogen peroxide. Studies were conducted on human brains obtained from autopsy of 9 heroin abusers and 8 controls. The level of GSH and the activity of glutathione-related enzymes were determined spectrophotometrically. The expression of GST pi on mRNA and protein level was studied by RT-PCR and Western blotting, respectively. The results indicated significant increase of GST and GSHPx activities, unchanged Se-GSHPx activity, and decreased level of GSH in frontal, temporal, parietal and occipital cortex, brain stem, hippocampus, and white matter of heroin abusers. GST pi expression was increased on both mRNA and protein levels, however the increase was lower in brain stem than in other regions. Heroin affects all regions of human brain, and especially brain stem. Its intoxication leads to an increase of organic rather then inorganic peroxides in various brain regions. Glutathione S-transferase plays an important role during heroin intoxication, however its protective effect is lower in brain stem than in brain cortex or hippocampus. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. 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.

  8. Glutathione and its antiaging and antimelanogenic effects

    Directory of Open Access Journals (Sweden)

    Weschawalit S

    2017-04-01

    Full Text Available Sinee Weschawalit,1 Siriwan Thongthip,2 Phanupong Phutrakool,3 Pravit Asawanonda1 1Department of Medicine, Division of Dermatology, 2Chula Clinical Research Center, 3Chula Data Management Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Previous studies showed that supplementation of reduced form of glutathione (GSH, 500 mg/d has a skin-lightening efficacy in humans. This study was designed to evaluate the influences of both GSH and oxidized form (GSSG, at doses lower than 500 mg/d, on improving skin properties. Patients and methods: A randomized, double-blind, placebo-controlled, parallel, three-arm study was conducted. Healthy female subjects were equally randomized into three groups and took GSH (250 mg/d, GSSG (250 mg/d, or placebo orally for 12 weeks. At each visit at baseline and for 12 weeks, skin features including melanin index, wrinkles, and other relevant biophysical properties were measured. Blood samples were collected for safety monitoring. Results: In generalized estimating equation analyses, melanin index and ultraviolet spots of all sites including face and arm when given GSH and GSSG tended to be lower than placebo. At some sites evaluated, subjects who received GSH showed a significant reduction in wrinkles compared with those taking placebo. A tendency toward increased skin elasticity was observed in GSH and GSSG compared with placebo. There were no serious adverse effects throughout the study. Conclusion: We showed that oral glutathione, 250 mg/d, in both reduced and oxidized forms effectively influences skin properties. Overall, glutathione in both forms are well tolerated. Keywords: glutathione, melanin, pigment, aging, wrinkle, whitening

  9. Cellular glutathione prevents cytolethality of monomethylarsonic acid

    International Nuclear Information System (INIS)

    Sakurai, Teruaki; Kojima, Chikara; Ochiai, Masayuki; Ohta, Takami; Sakurai, Masumi H.; Waalkes, Michael P.; Fujiwara, Kitao

    2004-01-01

    Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAs V ) and dimethylarsinic acid (DMAs V ). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAs V . We studied the molecular mechanisms of in vitro cytolethality of MMAs V using a rat liver epithelial cell line (TRL 1215). MMAs V was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAs V , but aminooxyacetic acid (AOAA), an inhibitor of β-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAs V in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAs V , although cellular GSH levels actually prevented the cytolethality of combined MMAs V and exogenous GSH. These findings indicate that human arsenic metabolite MMAs V is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects

  10. Potential Role of Amino Acid/Protein Nutrition and Exercise in Serum Albumin Redox State

    Directory of Open Access Journals (Sweden)

    Yasuaki Wada

    2017-12-01

    Full Text Available Albumin is the major protein in the serum of mammals. It is synthesized exclusively in the liver, before being secreted into the circulation. Similar to skeletal muscle protein, albumin synthesis is stimulated by dietary amino acids and proteins as well as exercise. Albumin has three isoforms based on the redox states of the free cysteine residue at position 34. The redox state of serum albumin has long been extensively investigated in terms of oxidative stress-related chronic diseases, with the redox state of serum albumin having been regarded as a marker of systemic oxidative stress. However, according to recent animal studies, the redox state of serum albumin is modulated by albumin turnover and may also reflect amino acid/protein nutritional status. Furthermore, as the redox state of serum albumin is modulated by exercise training, measuring the pre- and post-exercise redox states of serum albumin in athletes may be useful in assessing amino acid/protein nutritional status and exercise-induced oxidative stress, which are closely associated with skeletal muscle adaptive responses. This article extensively reviews serum albumin and the redox state of albumin in the context of amino acid/protein nutritional status and exercise training.

  11. 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.

  12. Bifunctional redox flow battery

    International Nuclear Information System (INIS)

    Wen, Y.H.; Cheng, J.; Xun, Y.; Ma, P.H.; Yang, Y.S.

    2008-01-01

    A new bifunctional redox flow battery (BRFB) system, V(III)/V(II)-L-cystine(O 2 ), was systematically investigated by using different separators. It is shown that during charge, water transfer is significantly restricted with increasing the concentration of HBr when the Nafion 115 cation exchange membrane is employed. The same result can be obtained when the gas diffusion layer (GDL) hot-pressed separator is used. The organic electro-synthesis is directly correlated with the crossover of vanadium. When employing the anion exchange membrane, the electro-synthesis efficiency is over 96% due to a minimal crossover of vanadium. When the GDL hot-pressed separator is applied, the crossover of vanadium and water transfer are noticeably prevented and the electro-synthesis efficiency of over 99% is obtained. Those impurities such as vanadium ions and bromine can be eliminated through the purification of organic electro-synthesized products. The purified product is identified to be L-cysteic acid by IR spectrum. The BRFB shows a favorable discharge performance at a current density of 20 mA cm -2 . Best discharge performance is achieved by using the GDL hot-pressed separator. The coulombic efficiency of 87% and energy efficiency of about 58% can be obtained. The cause of major energy losses is mainly associated with the cross-contamination of anodic and cathodic active electrolytes

  13. Redox rhythm reinforces the circadian clock to gate immune response.

    Science.gov (United States)

    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

    2015-07-23

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

  14. Redox-responsive theranostic nanoplatforms based on inorganic nanomaterials.

    Science.gov (United States)

    Han, Lu; Zhang, Xiao-Yong; Wang, Yu-Long; Li, Xi; Yang, Xiao-Hong; Huang, Min; Hu, Kun; Li, Lu-Hai; Wei, Yen

    2017-08-10

    Spurred on by advances in materials chemistry and nanotechnology, scientists have developed many novel nanopreparations for cancer diagnosis and therapy. To treat complex malignant tumors effectively, multifunctional nanomedicines with targeting ability, imaging properties and controlled drug release behavior should be designed and exploited. The therapeutic efficiency of loaded drugs can be dramatically improved using redox-responsive nanoplatforms which can sense the differences in the redox status of tumor tissues and healthy ones. Redox-sensitive nanocarriers can be constructed from both organic and inorganic nanomaterials; however, at present, drug delivery nanovectors progressively lean towards inorganic nanomaterials because of their facile synthesis/modification and their unique physicochemical properties. In this review, we focus specifically on the preparation and application of redox-sensitive nanosystems based on mesoporous silica nanoparticles (MSNs), carbon nanomaterials, magnetic nanoparticles, gold nanomaterials and other inorganic nanomaterials. We discuss relevant examples of redox-sensitive nanosystems in each category. Finally, we discuss current challenges and future strategies from the aspect of material design and practical application. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic β-cells.

    Science.gov (United States)

    Gray, Joshua P; Karandrea, Shpetim; Burgos, Delaine Zayasbazan; Jaiswal, Anil A; Heart, Emma A

    2016-11-16

    NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less-reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting in enhanced superoxide formation. However, to date, the roles of NQO1 and CYP450OR in pancreatic β-cell metabolism under basal conditions and oxidant challenge have not been characterized. Using NQO1 inhibition, over-expression and knock out, we have demonstrated that, in addition to protection of β-cells from toxic concentrations of the redox cycling quinone menadione, NQO1 also regulates the basal level of reduced-to-oxidized nucleotides, suggesting other role(s) beside that of an antioxidant enzyme. In contrast, over-expression of NADPH cytochrome P450 oxidoreductase (CYP450OR) resulted in enhanced redox cycling activity and decreased cellular viability, consistent with the enhanced generation of superoxide and H 2 O 2 . Basal expression of NQO1 and CYP450OR was comparable in isolated islets and liver. However, NQO1, but not CYP450OR, was strongly induced in β-cells exposed to menadione. NQO1 and CYP450OR exhibited a reciprocal preference for reducing equivalents in β-cells: while CYP450OR preferentially utilized NADPH, NQO1 primarily utilized NADH. Together, these results demonstrate that NQO1 and CYP450OR reciprocally regulate oxidant metabolism in pancreatic β-cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Thioredoxin-linked redox control of metabolism in Methanocaldococcus jannaschii, an evolutionarily deeply-rooted hyperthermophilic methanogenic archaeon

    Science.gov (United States)

    Thioredoxin (Trx), a small redox protein, controls multiple processes in eukaryotes and bacteria by changing the thiol redox status of selected proteins. We have investigated this aspect in methanarchaea. These ancient methanogens produce methane almost exclusively from H2 plus CO2 carried approxima...

  18. 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.

  19. 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 ...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

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

    Science.gov (United States)

    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.

  9. Quantitative redox imaging biomarkers for studying tissue metabolic state and its heterogeneity

    Directory of Open Access Journals (Sweden)

    He N. Xu

    2014-03-01

    Full Text Available NAD+/NADH redox state has been implicated in many diseases such as cancer and diabetes as well as in the regulation of embryonic development and aging. To fluorimetrically assess the mitochondrial redox state, Dr. Chance and co-workers measured the fluorescence of NADH and oxidized flavoproteins (Fp including flavin–adenine–dinucleotide (FAD and demonstrated their ratio (i.e. the redox ratio is a sensitive indicator of the mitochondrial redox states. The Chance redox scanner was built to simultaneously measure NADH and Fp in tissue at submillimeter scale in 3D using the freeze-trap protocol. This paper summarizes our recent research experience, development and new applications of the redox scanning technique in collaboration with Dr. Chance beginning in 2005. Dr. Chance initiated or actively involved in many of the projects during the last several years of his life. We advanced the redox scanning technique by measuring the nominal concentrations (in reference to the frozen solution standards of the endogenous fluorescent analytes, i.e., [NADH] and [Fp] to quantify the redox ratios in various biological tissues. The advancement has enabled us to identify an array of the redox indices as quantitative imaging biomarkers (including [NADH], [Fp], [Fp]/([NADH]+[Fp], [NADH]/[Fp], and their standard deviations for studying some important biological questions on cancer and normal tissue metabolism. We found that the redox indices were associated or changed with (1 tumorigenesis (cancer versus non-cancer of human breast tissue biopsies; (2 tumor metastatic potential; (3 tumor glucose uptake; (4 tumor p53 status; (5 PI3K pathway activation in pre-malignant tissue; (6 therapeutic effects on tumors; (7 embryonic stem cell differentiation; (8 the heart under fasting. Together, our work demonstrated that the tissue redox indices obtained from the redox scanning technique may provide useful information about tissue metabolism and physiology status in normal

  10. Effect of rosella ( Hibiscus sabdariffa L ) extract on glutathione-S ...

    African Journals Online (AJOL)

    Purpose: To determine the effect of rosella (Hibiscus sabdariffa L) extract on glutathione-S-trasferase (GST) activity and its hepatoprotective effect. Methods: A total of 25 rats were divided randomly into 5 groups (5 rats per group). Group I served as the baseline, group II was the negative control group, while groups III, IV and ...

  11. 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

  12. Superoxide radical (O2-) reactivity with respect to glutathione

    International Nuclear Information System (INIS)

    Sekaki, A.; Gardes-Albert, M.; Ferradini, C.

    1984-01-01

    Influence of superoxide radicals formed during gamma irradiation of glutathione in aerated aqueous solutions is examined. Solutions are buffered at pH7 and contain sodium formate for capture of H and OH radicals which are transformed in COO - radicals and then O 2 - radicals. G value of glutathione disparition vs glutathione concentration are given with and without enzyme or catalase. Reaction mechanism are interpreted [fr

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Redox regulation of calcium release in skeletal and cardiac muscle

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. The redox-Mannich reaction.

    Science.gov (United States)

    Chen, Weijie; Seidel, Daniel

    2014-06-06

    A complement to the classic three-component Mannich reaction, the redox-Mannich reaction, utilizes the same starting materials but incorporates an isomerization step that enables the facile preparation of ring-substituted β-amino ketones. Reactions occur under relatively mild conditions and are facilitated by benzoic acid.

  4. Differential alkylation-based redox proteomics – Lessons learnt

    Science.gov (United States)

    Wojdyla, Katarzyna; Rogowska-Wrzesinska, Adelina

    2015-01-01

    Cysteine is one of the most reactive amino acids. This is due to the electronegativity of sulphur atom in the side chain of thiolate group. It results in cysteine being present in several distinct redox forms inside the cell. Amongst these, reversible oxidations, S-nitrosylation and S-sulfenylation are crucial mediators of intracellular redox signalling, with known associations to health and disease. Study of their functionalities has intensified thanks to the development of various analytical strategies, with particular contribution from differential alkylation-based proteomics methods. Presented here is a critical evaluation of differential alkylation-based strategies for the analysis of S-nitrosylation and S-sulfenylation. The aim is to assess the current status and to provide insights for future directions in the dynamically evolving field of redox proteomics. To achieve that we collected 35 original research articles published since 2010 and analysed them considering the following parameters, (i) resolution of modification site, (ii) quantitative information, including correction of modification levels by protein abundance changes and determination of modification site occupancy, (iii) throughput, including the amount of starting material required for analysis. The results of this meta-analysis are the core of this review, complemented by issues related to biological models and sample preparation in redox proteomics, including conditions for free thiol blocking and labelling of target cysteine oxoforms. PMID:26282677

  5. Differential alkylation-based redox proteomics--Lessons learnt.

    Science.gov (United States)

    Wojdyla, Katarzyna; Rogowska-Wrzesinska, Adelina

    2015-12-01

    Cysteine is one of the most reactive amino acids. This is due to the electronegativity of sulphur atom in the side chain of thiolate group. It results in cysteine being present in several distinct redox forms inside the cell. Amongst these, reversible oxidations, S-nitrosylation and S-sulfenylation are crucial mediators of intracellular redox signalling, with known associations to health and disease. Study of their functionalities has intensified thanks to the development of various analytical strategies, with particular contribution from differential alkylation-based proteomics methods. Presented here is a critical evaluation of differential alkylation-based strategies for the analysis of S-nitrosylation and S-sulfenylation. The aim is to assess the current status and to provide insights for future directions in the dynamically evolving field of redox proteomics. To achieve that we collected 35 original research articles published since 2010 and analysed them considering the following parameters, (i) resolution of modification site, (ii) quantitative information, including correction of modification levels by protein abundance changes and determination of modification site occupancy, (iii) throughput, including the amount of starting material required for analysis. The results of this meta-analysis are the core of this review, complemented by issues related to biological models and sample preparation in redox proteomics, including conditions for free thiol blocking and labelling of target cysteine oxoforms. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Differential alkylation-based redox proteomics - Lessons learnt

    DEFF Research Database (Denmark)

    Wojdyla, Katarzyna; Rogowska-Wrzesinska, Adelina

    2015-01-01

    Cysteine is one of the most reactive amino acids. This is due to the electronegativity of sulphur atom in the side chain of thiolate group. It results in cysteine being present in several distinct redox forms inside the cell. Amongst these, reversible oxidations, S-nitrosylation and S-sulfenylati......Cysteine is one of the most reactive amino acids. This is due to the electronegativity of sulphur atom in the side chain of thiolate group. It results in cysteine being present in several distinct redox forms inside the cell. Amongst these, reversible oxidations, S-nitrosylation and S......-sulfenylation are crucial mediators of intracellular redox signalling, with known associations to health and disease. Study of their functionalities has intensified thanks to the development of various analytical strategies, with particular contribution from differential alkylation-based proteomics methods. Presented here...... is a critical evaluation of differential alkylation-based strategies for the analysis of S-nitrosylation and S-sulfenylation. The aim is to assess the current status and to provide insights for future directions in the dynamically evolving field of redox proteomics. To achieve that we collected 35 original...

  7. Glutathione attenuates uranyl toxicity in Lactococcus lactis

    Energy Technology Data Exchange (ETDEWEB)

    Fahmy, Karim; Oertel, Jana [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biophysics; Obeid, M. [Technische Univ. Dresden (Germany); Solioz, M. [Bern Univ. (Switzerland)

    2017-06-01

    We investigated the role of intracellular glutathione (GSH), which in a large number of taxa plays a role in the protection against the toxicity of heavy metals. Anaerobically grown Lactococcus lactis containing an inducible GSH synthesis pathway was used as a model organism allowing the study of GSH-dependent uranyl detoxification without interference from additional reactive oxygen species. Microcalorimetric measurements of the metabolic heat showed that intracellular GSH attenuates the toxicity of uranium at a concentration in the range of 10-150 μM. Isothermal titration calorimetry revealed the endothermic binding of U(VI) to the carboxyl group(s) of GSH. The data indicate that the primary detoxifying mechanism is the intracellular sequestration of carboxyl-coordinated U(VI) into an insoluble complex with GSH.

  8. Transport of glutathione into the nucleus.

    Science.gov (United States)

    Queval, Guillaume; Foyer, Christine

    2014-10-01

    The tripeptide thiol glutathione (GSH) is present in the nucleus of plant and animal cells. However, the functions of GSH in the nucleus remain poorly characterised. GSH appears to become sequestered in the nucleus at the early stages of the cell cycle. As part of our search for proteins that may be involved in GSH transport into the nucleus, we studied the functions of the nucleoporin called Alacrima Achalasia aDrenal Insufficiency Neurologic disorder (ALADIN). ALADIN is encoded by the Achalasia-Addisonianism-Alacrimia (AAAS) gene in mammalian cells. Defects in ALADIN promote adrenal disorders and lead to the triple A syndrome in humans. The ALADIN protein localizes to the nuclear envelope in Arabidopsis thaliana and interacts with other components of the nuclear pore complex (NPC). We characterised the functions of the ALADIN protein in an Arabidopsis thaliana T-DNA insertion knockout mutant, which shows slow growth compared to the wild type. Copyright © 2014. Published by Elsevier Inc.

  9. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-05-01

    The intracellular glutathione (GSH) content in HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulfoximine (BSO) or diethyl maleate (DEM). Clonogenicity, single strand DNA breaks (ssb) and double strand DNA breaks (dsb) were used as criteria for radiation induced damage after X- or γ irradiation. In survival experiments DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the OER was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (Auth.)

  10. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-01-01

    The intracellular glutathione (GSH) content of HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulphoximine or diethyl maleate (DEM). Clonogenicity, single-strand DNA breaks (ssb) and double-strand DNA breaks (dsb) were used as criteria for radiation-induced damage after X- or γ-irradiation. In survival experiments, DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the o.e.r. was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (author)

  11. Misonidazole-glutathione conjugates in CHO cells

    International Nuclear Information System (INIS)

    Varghese, A.J.; Whitmore, G.F.

    1984-01-01

    Misonidazole, after reduction to the hydroxylamine derivative, reacts with glutathione (GSH) under physiological conditions. The reaction product has been identified as a mixture of two isomeric conjugates. When water soluble extracts of CHO cells exposed to misonidazole under hypoxic conditions are subjected to HPLC analysis, misonidazole derivatives, having the same chromatographic properties as the GSH-MISO conjugates, were detected. When CHO cells were incubated with misonidazole in the presence of added GSH, a substantial increase in the amount of the conjugate was detected. When extracts of CHO cells exposed to misonidazole under hypoxia were subsequently exposed to GSH, an increased formation of the conjugate was observed. A rearrangement product of the hydroxylamine derivative of misonidazole is postulated as the reactive intermediate responsible for the formation of the conjugate

  12. Glutathione attenuates uranyl toxicity in Lactococcus lactis

    International Nuclear Information System (INIS)

    Fahmy, Karim; Oertel, Jana; Solioz, M.

    2017-01-01

    We investigated the role of intracellular glutathione (GSH), which in a large number of taxa plays a role in the protection against the toxicity of heavy metals. Anaerobically grown Lactococcus lactis containing an inducible GSH synthesis pathway was used as a model organism allowing the study of GSH-dependent uranyl detoxification without interference from additional reactive oxygen species. Microcalorimetric measurements of the metabolic heat showed that intracellular GSH attenuates the toxicity of uranium at a concentration in the range of 10-150 μM. Isothermal titration calorimetry revealed the endothermic binding of U(VI) to the carboxyl group(s) of GSH. The data indicate that the primary detoxifying mechanism is the intracellular sequestration of carboxyl-coordinated U(VI) into an insoluble complex with GSH.

  13. Radioimmunoassays for catalase and glutathion peroxidase

    International Nuclear Information System (INIS)

    Baret, A.; Courtiere, A.; Lorry, D.; Puget, K.; Michelson, A.M.

    1982-01-01

    Specific and sensitive radioimmunoassays for human, bovine and rat catalase (CAT) and glutathion Peroxidase (GPX) are described. The obtained values are expressed as enzymatic units per μg of immunoreactive protein. They appear to closely correspond to specific activities of the purified enzymes determined by colorimetric protein-assay. Indeed, the values of the specific activities of purified human CAT is 57.9 k/mg and that of purified rat GPX is 180 units/mg. This result validates the present RIAs and the association of the two techniques allows the determination of a further parameter. In conclusion, RIAs for CAT and GPX can be applied with great specificity and sensitivity to a wide variety of human, rat and bovine medias

  14. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation.

    Science.gov (United States)

    Wang, Kui; Zhang, Tao; Dong, Qiang; Nice, Edouard Collins; Huang, Canhua; Wei, Yuquan

    2013-03-14

    Stem cells are characterized by their unique ability of self-renewal to maintain the so-called stem cell pool. Over the past decades, reactive oxygen species (ROS) have been recognized as toxic aerobic metabolism byproducts that are harmful to stem cells, leading to DNA damage, senescence or cell death. Recently, a growing body of literature has shown that stem cells reside in redox niches with low ROS levels. The balance of Redox homeostasis facilitates stem cell self-renewal by an intricate network. Thus, to fully decipher the underlying molecular mechanisms involved in the maintenance of stem cell self-renewal, it is critical to address the important role of redox homeostasis in the regulation of self-renewal and differentiation of stem cells. In this regard, we will discuss the regulatory mechanisms involved in the subtly orchestrated balance of redox status in stem cells by scavenger antioxidant enzyme systems that are well monitored by the hypoxia niches and crucial redox regulators including forkhead homeobox type O family (FoxOs), apurinic/apyrimidinic (AP) endonuclease1/redox factor-1 (APE1/Ref-1), nuclear factor erythroid-2-related factor 2 (Nrf2) and ataxia telangiectasia mutated (ATM). We will also introduce several pivotal ROS-sensitive molecules, such as hypoxia-inducible factors, p38 mitogen-activated protein kinase (p38) and p53, involved in the redox-regulated stem cell self-renewal. Specifically, all the aforementioned molecules can act as 'redox sensors' by virtue of redox modifications of their cysteine residues, which are critically important in the control of protein function. Given the importance of redox homeostasis in the regulation of stem cell self-renewal, understanding the underlying molecular mechanisms involved will provide important new insights into stem cell biology.

  15. Response of Glutathione and Glutathione S-transferase in Rice Seedlings Exposed to Cadmium Stress

    Directory of Open Access Journals (Sweden)

    Chun-hua ZHANG

    2008-03-01

    Full Text Available A hydroponic culture experiment was done to investigate the effect of Cd stress on glutathione content (GSH and glutathione S-transferase (GST, EC 2.5.1.18 activity in rice seedlings. The rice growth was severely inhibited when Cd level in the solution was higher than 10 mg/L. In rice shoots, GSH content and GST activity increased with the increasing Cd level, while in roots, GST was obviously inhibited by Cd treatments. Compared with shoots, the rice roots had higher GSH content and GST activity, indicating the ability of Cd detoxification was much higher in roots than in shoots. There was a significant correlation between Cd level and GSH content or GST activity, suggesting that both parameters may be used as biomarkers of Cd stress in rice.

  16. 21 CFR 864.7375 - Glutathione reductase assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Glutathione reductase assay. 864.7375 Section 864.7375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione...

  17. Glutathione Transferase GSTπ In Breast Tumors Evaluated By Three Techniques

    Directory of Open Access Journals (Sweden)

    Rafael Molina

    1993-01-01

    Full Text Available The glutathione transferases are involved in intracellular detoxification reactions. One of these, GSTπ, is elevated in some breast cancer cells, particularly cells selected for resistance to anticancer agents. We evaluated GSTπ expression in 60 human breast tumors by three techniques, immunohistochemistry, Northern hybridization, and Western blot analysis. There was a significant positive correlation between the three methods, with complete concordance seen in 64% of the tumors. There was strong, inverse relationship between GSTπ expression and steroid receptor status with all of the techniques utili zed. [n addition, there was a trend toward higher GSTπ expression in poorly differentiated tumors, but no correlation was found between tumor GSTπ content and DNA ploidy or %S-phase. GSTπ expression was also detected in adjacent benign breast tissue as well as infiltrating lymphocytes; this expression may contribute to GSTπ measurements using either Northern hybridization or Western blot analysis. These re sults suggest that immunohistochemistry is the method of choice for measuring GSTπ in breast tumors.

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

    Science.gov (United States)

    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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. The Redox Balance in Erythrocytes, Plasma, and Periosteum of Patients with Titanium Fixation of the Jaw

    Directory of Open Access Journals (Sweden)

    Jan Borys

    2017-06-01

    Full Text Available Titanium miniplates and screws are commonly used for fixation of jaw fractured or osteotomies. Despite the opinion of their biocompatibility, in clinical practice symptoms of chronic inflammation around the fixation develop in some patients, even many years after the application of miniplates and screws. The cause of these complications is still an unanswered question. Taking into account that oxidative stress is one of the toxic action of titanium, we have evaluated the antioxidant barrier as well as oxidative stress in the erythrocytes, plasma and periosteum covering the titanium fixation of the jaw. The study group was composed of 32 patients aged 20–30 with inserted miniplates and screws. The antioxidant defense: catalase (CAT, glutathione peroxidase (GPx, superoxide dismutase-1 (SOD1, uric acid (UA, total antioxidant capacity (TAC, as well as oxidative damage products: advanced oxidation protein products (AOPP, advanced glycation end products (AGE, dityrosine, kynurenine, N-formylkynurenine, tryptophan, malondialdehyde (MDA, 4-hydroxynonenal (4-HNE, total oxidant status (TOS, and oxidative status index (OSI were evaluated. SOD1 activity (↓37%, and tryptophan levels (↓34% showed a significant decrease while AOPP (↑25%, TOS (↑80% and OSI (↑101% were significantly elevated in maxillary periosteum of patients who underwent bimaxillary osteotomies as compared to the control group. SOD-1 (↓55%, TAC (↓58.6%, AGE (↓60% and N-formylkynurenine (↓34% was statistically reduced while AOPP (↑38%, MDA (↑29%, 4-HNE (↑114%, TOS (↑99%, and OSI (↑381% were significantly higher in the mandibular periosteum covering miniplates/screw compared with the control tissues. There were no correlations between antioxidants and oxidative stress markers in the periosteum of all patients and the blood. As exposure to the Ti6Al4V titanium alloy leads to disturbances of redox balance in the periosteum surrounding titanium implants of the maxilla

  5. Chemistry and Redox Biology of Mycothiol.

    Science.gov (United States)

    Reyes, Aníbal M; Pedre, Brandán; De Armas, María Inés; Tossounian, Maria-Armineh; Radi, Rafael; Messens, Joris; Trujillo, Madia

    2018-02-20

    Mycothiol (MSH, AcCys-GlcN-Ins) is the main low-molecular weight (LMW) thiol of most Actinomycetes, including the human pathogen Mycobacterium tuberculosis that affects millions of people worldwide. Strains with decreased MSH content show increased susceptibilities to hydroperoxides and electrophilic compounds. In M. tuberculosis, MSH modulates the response to several antituberculosis drugs. Enzymatic routes involving MSH could provide clues for specific drug design. Recent Advances: Physicochemical data argue against a rapid, nonenzymatic reaction of MSH with oxidants, disulfides, or electrophiles. Moreover, exposure of the bacteria to high concentrations of two-electron oxidants resulted in protein mycothiolation. The recently described glutaredoxin-like protein mycoredoxin-1 (Mrx-1) provides a route for catalytic reduction of mycothiolated proteins, protecting critical cysteines from irreversible oxidation. The description of MSH/Mrx-1-dependent activities of peroxidases helped to explain the higher susceptibility to oxidants observed in Actinomycetes lacking MSH. Moreover, the first mycothiol-S-transferase, member of the DinB superfamily of proteins, was described. In Corynebacterium, both the MSH/Mrx-1 and the thioredoxin pathways reduce methionine sulfoxide reductase A. A novel tool for in vivo imaging of the MSH/mycothiol disulfide (MSSM) status allows following changes in the mycothiol redox state during macrophage infection and its relationship with antibiotic sensitivity. Redundancy of MSH with other LMW thiols is starting to be unraveled and could help to rationalize the differences in the reported importance of MSH synthesis observed in vitro versus in animal infection models. Future work should be directed to establish the structural bases of the specificity of MSH-dependent enzymes, thus facilitating drug developments. Antioxid. Redox Signal. 28, 487-504.

  6. Comparison of plasma malondialdehyde, glutathione, glutathione peroxidase, hydroxyproline and selenium levels in patients with vitiligo and healthy controls

    Directory of Open Access Journals (Sweden)

    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.

  7. Interactions of [alpha,beta]-unsaturated carbonyl compounds with the glutathione-related biotransformation system

    NARCIS (Netherlands)

    Iersel, van M.L.P.S.

    1998-01-01

    Introduction
    Modulation of glutathione-related biotransformation steps may play a role in important phenomena as anticarcinogenicity and multidrug resistance. Glutathione-related biotransformation comprises three main aspects i.e. glutathione, the

  8. Cascade redox flow battery systems

    Science.gov (United States)

    Horne, Craig R.; Kinoshita, Kim; Hickey, Darren B.; Sha, Jay E.; Bose, Deepak

    2014-07-22

    A reduction/oxidation ("redox") flow battery system includes a series of electrochemical cells arranged in a cascade, whereby liquid electrolyte reacts in a first electrochemical cell (or group of cells) before being directed into a second cell (or group of cells) where it reacts before being directed to subsequent cells. The cascade includes 2 to n stages, each stage having one or more electrochemical cells. During a charge reaction, electrolyte entering a first stage will have a lower state-of-charge than electrolyte entering the nth stage. In some embodiments, cell components and/or characteristics may be configured based on a state-of-charge of electrolytes expected at each cascade stage. Such engineered cascades provide redox flow battery systems with higher energy efficiency over a broader range of current density than prior art arrangements.

  9. The NASA Redox Storage System Development project, 1980

    Science.gov (United States)

    1982-12-01

    The technical accomplishments pertaining to the development of Redox systems and related technology are outlined in terms of the task elements: prototype systems development, application analyses, and supporting technology. Prototype systems development provides for a major procurement to develop an industrial capability to take the current NASA Lewis technology and go on to the design, development, and commercialization of iron-chromium Redox storage systems. Application analyses provides for the definition of application concepts and technology requirements, specific definition studies, and the identification of market sectors and their penetration potential. Supporting technology includes both in house and contractual efforts that encompass implementation of technology improvements in membranes, electrodes, reactant processing, and system design. The status of all elements is discussed.

  10. Glutathione level after long-term occupational elemental mercury exposure

    International Nuclear Information System (INIS)

    Kobal, Alfred Bogomir; Prezelj, Marija; Horvat, Milena; Krsnik, Mladen; Gibicar, Darija; Osredkar, Josko

    2008-01-01

    Many in vitro and in vivo studies have elucidated the interaction of inorganic mercury (Hg) and glutathione. However, human studies are limited. In this study, we investigated the potential effects of remote long-term intermittent occupational elemental Hg vapour (Hg o ) exposure on erythrocyte glutathione levels and some antioxidative enzyme activities in ex-mercury miners in the period after exposure. The study included 49 ex-mercury miners divided into subgroups of 28 still active, Hg o -not-exposed miners and 21 elderly retired miners, and 41 controls, age-matched to the miners subgroup. The control workers were taken from 'mercury-free works'. Reduced glutathione (GSH) and oxidized disulphide glutathione (GSSG) concentrations in haemolysed erythrocytes were determined by capillary electrophoresis, while total glutathione (total GSH) and the GSH/GSSG ratio were calculated from the determined values. Catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in erythrocytes were measured using commercially available reagent kits, while urine Hg (U-Hg) concentrations were determined by cold vapour atomic absorption (CVAAS). No correlation of present U-Hg levels, GSH, GSSG, and antioxidative enzymes with remote occupational biological exposure indices were found. The mean CAT activity in miners and retired miners was significantly higher (p o could be an inductive and additive response to maintain the balance between GSH and antioxidative enzymes in interaction with the Hg body burden accumulated during remote occupational exposure, which does not represent a severely increased oxidative stress

  11. Redox reaction studies by nanosecond pulse radiolysis

    International Nuclear Information System (INIS)

    Moorthy, P.N.

    1979-01-01

    Free radicals are formed as intermediates in many chemical and biochemical reactions. An important type of reaction which they can undergo is a one electron or redox process. The direction and rate of such electron transfer reactions is governed by the relative redox potentials of the participating species. Because of the generally short lived nature of free radicals, evaluation of their redox potentials poses a number of problems. Two techniques are described for the experimental determination of the redox potentials of short lived species generated by either a nanosecond electron pulse or laser flash. In the first method, redox titration of the short lived species with stable molecules of known redox potential is carried out, employing the technique of fast kinetic spectrophotometry. Conversely, by the same method it is also possible to evaluate the one electron redox potentials of stable molecules by redox titration with free radicals of known redox potential produced as above. In the second method, electrochemical reduction or oxidation of the short lived species at an appropriate electrode (generally a mercury drop) is carried out at different fixed potentials, and the redox potential evaluated from the current-potential curves (polarograms). Full description of the experimental set up and theoretical considerations for interpretation of the raw data are given. The relative merits of the two methods and their practical applicability are discussed. (auth.)

  12. Dissecting Redox Biology Using Fluorescent Protein Sensors.

    Science.gov (United States)

    Schwarzländer, Markus; Dick, Tobias P; Meyer, Andreas J; Morgan, Bruce

    2016-05-01

    Fluorescent protein sensors have revitalized the field of redox biology by revolutionizing the study of redox processes in living cells and organisms. Within one decade, a set of fundamental new insights has been gained, driven by the rapid technical development of in vivo redox sensing. Redox-sensitive yellow and green fluorescent protein variants (rxYFP and roGFPs) have been the central players. Although widely used as an established standard tool, important questions remain surrounding their meaningful use in vivo. We review the growing range of thiol redox sensor variants and their application in different cells, tissues, and organisms. We highlight five key findings where in vivo sensing has been instrumental in changing our understanding of redox biology, critically assess the interpretation of in vivo redox data, and discuss technical and biological limitations of current redox sensors and sensing approaches. We explore how novel sensor variants may further add to the current momentum toward a novel mechanistic and integrated understanding of redox biology in vivo. Antioxid. Redox Signal. 24, 680-712.

  13. 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.

  14. Nucleation behavior of glutathione polymorphs in water

    International Nuclear Information System (INIS)

    Chen, Zhi; Dang, Leping; Li, Shuai; Wei, Hongyuan

    2013-01-01

    Nucleation behavior of glutathione (GSH) polymorphs in water was investigated by experimental method combined with classical nucleation theory. The solubility of α and β forms GSH in water at different temperatures, and the nucleation induction period at various supersaturations and temperatures were determined experimentally. The results show that, in a certain range of supersaturation, the nucleation of β form predominates at relatively higher temperature, while α form will be obtained at lower temperature. The nucleation kinetics parameters of α and β form were then calculated. To understand the crucial role of temperature on crystal forms, “hypothetic” nucleation parameters of β form at 283.15 K were deduced based on extrapolation method. The results show that the interfacial tension, critical free energy, critical nucleus radius and nucleus number of α form are smaller than that of β form in the same condition at 283.15 K, which implies that α form nucleates easier than β form at low temperature. This work may be useful for the control and optimization of GSH crystallization process in industry

  15. Labor Augmentation with Oxytocin Decreases Glutathione Level

    Directory of Open Access Journals (Sweden)

    Naomi Schneid-Kofman

    2009-01-01

    Full Text Available Objective. To compare oxidative stress following spontaneous vaginal delivery with that induced by Oxytocin augmented delivery. Methods. 98 women recruited prior to labor. 57 delivered spontaneously, while 41 received Oxytocin for augmentation of labor. Complicated deliveries and high-risk pregnancies were excluded. Informed consent was documented. Arterial cord blood gases, levels of Hematocrit, Hemoglobin, and Bilirubin were studied. Glutathione (GSH concentration was measured by a spectroscopic method. Plasma and red blood cell (RBC levels of Malondialdehyde indicated lipid peroxidation. RBC uptake of phenol red denoted cell penetrability. SPSS data analysis was used. Results. Cord blood GSH was significantly lower in the Oxytocin group (2.3±0.55 mM versus 2.55±0.55 mM, =.01. No differences were found in plasma or RBC levels of MDA or in uptake of Phenol red between the groups. Conclusion. Lower GSH levels following Oxytocin augmentation indicate an oxidative stress, though selected measures of oxidative stress demonstrate no cell damage.

  16. The Genetic Architecture of Murine Glutathione Transferases.

    Directory of Open Access Journals (Sweden)

    Lu Lu

    Full Text Available Glutathione S-transferase (GST genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6 and DBA2/J (D2--the BXD family--was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01 with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes.

  17. 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...

  18. Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

    Science.gov (United States)

    Miao, Lu; Holley, Aaron K.; Zhao, Yanming; St. Clair, William H.

    2014-01-01

    Abstract Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)–generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481–1500. PMID:24093432

  19. 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.

  20. Radiation-induced disruption of hippocampal redox homeostasis, neurogenesis and cognitive function: protective role of melatonin and its metabolites

    International Nuclear Information System (INIS)

    Manda, Kailash

    2012-01-01

    The sensitivity of neuronal tissues to ionizing radiation depends on the rate of differentiation and accompanying factors of the tissues as well as on the efficiency of the intrinsic antioxidative defense systems. Neurogenic area in the adult brain are reported be highly sensitive to ionizing radiation. While the pathogenesis of radiation induced cognitive impairment is not well understood, recent studies indicated that neuronal precursor cells in the hippocampus may be involved. The dentate gyrus of the hippocampus is unique in that it is one of two regions in the mammalian brain that continues to produce new neurons in adulthood. Moreover, brain is considered abnormally sensitive to oxidative damage and in fact early studies demonstrating the ease of peroxidation of brain membranes supported this notion. Brain is enriched in the more easily peroxidizable fatty acids, consumes an inordinate fraction (20%) of the total oxygen consumption for its relatively small weight (2%), and is not particularly enriched in antioxidant defenses. Our recent findings showed an inverse relationship between mice cognitive performance and cellular indicators of oxidative stress or redox status which was reported in the term glutathione homeostasis (GSH/GSSG), DNA damage, protein oxidation and lipid peroxidation. Radiation exposure severely impaired the hipocampal neurogenesis as measure in the terms of immunoreactivity of immature and proliferating neurons in dentate gyrus, the doublecortin (Dcx) and Ki-67 positive cells respectively. Our results showed a significant implication of hippocampus neurogenesis in cognitive functions and pre-treatment of melatonin and its metabolites significantly protected the neurogenic potential of brain and thereby the cognitive functions. (author)

  1. Engineering redox balance through cofactor systems.

    Science.gov (United States)

    Chen, Xiulai; Li, Shubo; Liu, Liming

    2014-06-01

    Redox balance plays an important role in the production of enzymes, pharmaceuticals, and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximal carbon flux towards target metabolites with no fluctuations in redox. This requires functional cofactor systems that support dynamic homeostasis between different redox states or functional stability in a given redox state. Redox balance can be achieved by improving the self-balance of a cofactor system, regulating the substrate balance of a cofactor system, and engineering the synthetic balance of a cofactor system. This review summarizes how cofactor systems can be manipulated to improve redox balance in microbes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Radii of Redox Components from Absolute Redox Potentials Compared with Covalent and Aqueous Ionic Radii

    Czech Academy of Sciences Publication Activity Database

    Heyrovská, Raji

    2010-01-01

    Roč. 22, č. 9 (2010), s. 903-907 ISSN 1040-0397 Institutional support: RVO:68081707 Keywords : Electrochemistry * Absolute redox potentials * Radii of redox components Subject RIV: BO - Biophysics Impact factor: 2.721, year: 2010

  3. Redox Pioneer: Professor Vadim N. Gladyshev.

    Science.gov (United States)

    Hatfield, Dolph L

    2016-07-01

    Professor Vadim N. Gladyshev is recognized here as a Redox Pioneer, because he has published an article on antioxidant/redox biology that has been cited more than 1000 times and 29 articles that have been cited more than 100 times. Gladyshev is world renowned for his characterization of the human selenoproteome encoded by 25 genes, identification of the majority of known selenoprotein genes in the three domains of life, and discoveries related to thiol oxidoreductases and mechanisms of redox control. Gladyshev's first faculty position was in the Department of Biochemistry, the University of Nebraska. There, he was a Charles Bessey Professor and Director of the Redox Biology Center. He then moved to the Department of Medicine at Brigham and Women's Hospital, Harvard Medical School, where he is Professor of Medicine and Director of the Center for Redox Medicine. His discoveries in redox biology relate to selenoenzymes, such as methionine sulfoxide reductases and thioredoxin reductases, and various thiol oxidoreductases. He is responsible for the genome-wide identification of catalytic redox-active cysteines and for advancing our understanding of the general use of cysteines by proteins. In addition, Gladyshev has characterized hydrogen peroxide metabolism and signaling and regulation of protein function by methionine-R-sulfoxidation. He has also made important contributions in the areas of aging and lifespan control and pioneered applications of comparative genomics in redox biology, selenium biology, and aging. Gladyshev's discoveries have had a profound impact on redox biology and the role of redox control in health and disease. He is a true Redox Pioneer. Antioxid. Redox Signal. 25, 1-9.

  4. Characterization of redox proteins using electrochemical methods

    OpenAIRE

    Verhagen, M.

    1995-01-01

    The use of electrochemical techniques in combination with proteins started approximately a decade ago and has since then developed into a powerfull technique for the study of small redox proteins. In addition to the determination of redox potentials, electrochemistry can be used to obtain information about the kinetics of electron transfer between proteins and about the dynamic behaviour of redox cofactors in proteins. This thesis describes the results of a study, initiated to get a ...

  5. Redox flow batteries having multiple electroactive elements

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; Li, Liyu; Yang, Zhenguo; Nie, Zimin

    2018-05-01

    Introducing multiple redox reactions with a suitable voltage range can improve the energy density of redox flow battery (RFB) systems. One example includes RFB systems utilizing multiple redox pairs in the positive half cell, the negative half cell, or in both. Such RFB systems can have a negative electrolyte, a positive electrolyte, and a membrane between the negative electrolyte and the positive electrolyte, in which at least two electrochemically active elements exist in the negative electrolyte, the positive electrolyte, or both.

  6. Membranes for Redox Flow Battery Applications

    OpenAIRE

    Prifti, Helen; Parasuraman, Aishwarya; Winardi, Suminto; Lim, Tuti Mariana; Skyllas-Kazacos, Maria

    2012-01-01

    The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. Th...

  7. Hemoglobin-catalyzed fluorometric method for the determination of glutathione

    Science.gov (United States)

    Wang, Ruiqiang; Tang, Lin; Li, Hua; Wang, Yi; Gou, Rong; Guo, Yuanyuan; Fang, Yudong; Chen, Fengmei

    2016-01-01

    A new spectrofluorometric method for the determination of glutathione based on the reaction catalyzed by hemoglobin was reported. The reaction product gave a highly fluorescent intensity with the excitation and emission wavelengths of 320.0 nm and 413.0 nm, respectively. The optimum experimental conditions were investigated. Results showed that low concentration glutathione enhanced the fluorescence intensity significantly. The line ranges were 1.0 × 10-6-1.0 × 10-5 mol L-1 of glutathione and 6.0 × 10-10 mol L-1-1.0 × 10-8 mol L-1, respectively. The detection limit was calculated to be 1.1 × 10-11 mol L-1. The recovery test by the standard addition method gave values in the range of 90.78%-102.20%. This method was used for the determination of glutathione in synthetic and real samples with satisfactory results.

  8. Oxidative Stress Markers and Genetic Polymorphisms of Glutathione ...

    African Journals Online (AJOL)

    2017-10-26

    Oct 26, 2017 ... stress such as asthma, lung cancer, and type 2 diabetes mellitus.[11-13]. Although ... epigenetic, and environmental factors. Little is known ..... glutathione Stransferase genes increase risk of prostate cancer biochemical ...

  9. Glutathione transferase mimics : Micellar catalysis of an enzymic reaction

    NARCIS (Netherlands)

    Lindkvist, Björn; Weinander, Rolf; Engman, Lars; Koetse, Marc; Engberts, Jan B.F.N.; Morgenstern, Ralf

    1997-01-01

    Substances that mimic the enzyme action of glutathione transferases (which serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nitroarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic

  10. Electrolyte ions and glutathione enzymes as stress markers in ...

    African Journals Online (AJOL)

    Electrolyte ions and glutathione enzymes as stress markers in Argania spinosa subjected to drought stress and recovery. ... By Country · List All Titles · Free To Read Titles This Journal is Open Access. Featuring journals from 32 Countries:.

  11. Inhibition of glutathione S-transferases (GSTs) activity from cowpea ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... Inhibition effect of the plant extracts on the GST was studied by spectrophotometric method. The ... of assuring food security in developing countries like ..... studies on African cat fish (Clarias gariepinus) liver glutathione s-.

  12. 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

  13. Fluorescence detection of glutathione and oxidized glutathione in blood with a NIR-excitable cyanine probe

    Science.gov (United States)

    Liu, Chang-hui; Qi, Feng-pei; Wen, Fu-bin; Long, Li-ping; Liu, Ai-juan; Yang, Rong-hua

    2018-04-01

    Cyanine has been widely utilized as a near infrared (NIR) fluorophore for detection of glutathione (GSH). However, the excitation of most of the reported cyanine-based probes was less than 800 nm, which inevitably induce biological background absorption and lower the sensitivity, limiting their use for detection of GSH in blood samples. To address this issue, here, a heptamethine cyanine probe (DNIR), with a NIR excitation wavelength at 804 nm and a NIR emission wavelength at 832 nm, is employed for the detection of GSH and its oxidized form (GSSG) in blood. The probe displays excellent selectivity for GSH over GSSG and other amino acids, and rapid response to GSH, in particular a good property for indirect detection of GSSG in the presence of enzyme glutathione reductase and the reducing agent nicotinamideadenine dinucleotide phosphate, without further separation prior to fluorescent measurement. To the best of our knowledge, this is the first attempt to explore NIR fluorescent approach for the simultaneous assay of GSH and GSSG in blood. As such, we expect that our fluorescence sensors with both NIR excitation and NIR emission make this strategy suitable for the application in complex physiological systems.

  14. Intracellular thiol levels and radioresistance: Studies with glutathione and glutathione mono ethyl ester

    International Nuclear Information System (INIS)

    Astor, M.B.; Meister, A.; Anderson, M.E.

    1987-01-01

    Intracellular thiols such as glutathione (GSH) protect cells against free radicals formed during oxidative metabolism or from exposure to drugs or ionizing radiation. The role of intracellular GSH in the repair of radiation induced free radical damage was studied using GSH or its analog glutathione mono ethyl ester (GEE), which readily penetrates into the cell. Chinese hamster V79 cells with normal GSH levels were afforded equal protection under aerated and hypoxic conditions (DMF = 1.2 OER = 3.7) by both 10 mM GSH and GEE although GEE had raised interacellular GSH levels three-fold. Growth of V79 cells in cysteine free media resulted in undetectable levels of GSH and OER of 2.2 with no change in aerated survival. Restoration of intracellular GSH by 10 mM GEE resulted in an increase of the OER from 2.2. to 3.8 (DMF = 1.7). Only 14% of the intracellular GSH needs to be repleted to give an OER of 3.0. These experiments provide evidence that thiols do play a role in the oxygen effect and are present at levels in excess of what is necessary for maximal radioprotection

  15. Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

    Science.gov (United States)

    Gong, Zhen-Hua; Tian, Guo-Li; Huang, Qi-Wei; Wang, Yan-Min; Xu, Hong-Ping

    2017-07-20

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 μmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 μmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

  16. Subcellular distribution of glutathione and cysteine in cyanobacteria

    OpenAIRE

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

    2010-01-01

    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,...

  17. Redox reactions in food fermentations

    DEFF Research Database (Denmark)

    Hansen, Egon Bech

    2018-01-01

    involves oxidative steps in the early part of the pathways whereas a multitude of different reactions are used as compensating reductions. Much of the diversity seen between food fermentations arise from the different routes and the different electron acceptors used by microorganisms to counterbalance...... and this contributes to the diversity in flavor, color, texture, and shelf life. The review concludes that these reactions are still only incompletely understood and that they represent an interesting area for fundamental research and also represent a fertile field for product development through a more conscious use...... of the redox properties of strains used to compose food cultures....

  18. Method for producing redox shuttles

    Science.gov (United States)

    Pupek, Krzysztof Z.; Dzwiniel, Trevor L.; Krumdick, Gregory K.

    2015-03-03

    A single step method for producing a redox shuttle having the formula 2,5-di-tert-butyl-1,4-phenylene tetraethyl bis(phosphate) is provided, the method comprising phosphorylating tert butyl hydroquinone with a phosphate-containing reagent. Also provided is method for producing 2,5-di-tert-butyl-1,4-phenylene tetraethyl bis(phosphate), the method comprising solubilizing tert-butyl hydroquinone and tetrabutylammonium bromide with methyltetrahydrofuran to create a mixture; heating the mixture while adding base to the mixture in an amount to turn the mixture orange; and adding diethyl chlorophosphate to the orange mixture in an amount to phosphorylate the hydroquinone.

  19. Free Radicals and Antioxidant Status in Protein Energy Malnutrition

    Directory of Open Access Journals (Sweden)

    M. Khare

    2014-01-01

    Full Text Available Background/Objectives. The aim of this study was to evaluate oxidant and antioxidant status in children with different grades of Protein Energy Malnutrition (PEM. Subjects/Methods. A total of two hundred fifty (250 children (age range: 6 months to 5 years living in eastern UP, India, were recruited. One hundred and ninety-three (193 of these children had different grades of PEM (sixty-five (65 children belong to mild, sixty (60 to moderate, and sixty-eight (68 to severe group. Grading in group was done after standardization in weight and height measurements. Fifty-seven (57 children who are age and and sex matched, healthy, and well-nourished were recruited from the local community and used as controls after checking their protein status (clinical nutritional status with height and weight standardization. Redox homeostasis was assessed using spectrophotometric/colorimetric methods. Results. In our study, erythrocyte glutathione (GSH, plasma Cu, Zn-superoxide dismutase (Cu,Zn-SOD,EC 1.15.1.1, ceruloplasmin (Cp, and ascorbic acid were significantly (P<0.001 more decreased in children with malnutrition than controls. Plasma malondialdehyde (MDA, and protein carbonyl (PC were significantly (P<0.001 raised in cases as compared to controls. Conclusion. Stress is created as a result of PEM which is responsible for the overproduction of reactive oxygen species (ROSs. These ROSs will lead to membrane oxidation and thus an increase in lipid peroxidation byproducts such as MDA and protein oxidation byproducts such as PC mainly. Decrease in level of antioxidants suggests an increased defense against oxidant damage. Changes in oxidant and antioxidant levels may be responsible for grading in PEM.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Thiol-based redox signaling in the nitrogen-fixing symbiosis

    Directory of Open Access Journals (Sweden)

    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

  3. 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.

  4. Information processing through a bio-based redox capacitor: signatures for redox-cycling.

    Science.gov (United States)

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

    2014-08-01

    Redox-cycling compounds can significantly impact biological systems and can be responsible for activities that range from pathogen virulence and contaminant toxicities, to therapeutic drug mechanisms. Current methods to identify redox-cycling activities rely on the generation of reactive oxygen species (ROS), and employ enzymatic or chemical methods to detect ROS. Here, we couple the speed and sensitivity of electrochemistry with the molecular-electronic properties of a bio-based redox-capacitor to generate signatures of redox-cycling. The redox capacitor film is electrochemically-fabricated at the electrode surface and is composed of a polysaccharide hydrogel with grafted catechol moieties. This capacitor film is redox-active but non-conducting and can engage diffusible compounds in either oxidative or reductive redox-cycling. Using standard electrochemical mediators ferrocene dimethanol (Fc) and Ru(NH3)6Cl3 (Ru(3+)) as model redox-cyclers, we observed signal amplifications and rectifications that serve as signatures of redox-cycling. Three bio-relevant compounds were then probed for these signatures: (i) ascorbate, a redox-active compound that does not redox-cycle; (ii) pyocyanin, a virulence factor well-known for its reductive redox-cycling; and (iii) acetaminophen, an analgesic that oxidatively redox-cycles but also undergoes conjugation reactions. These studies demonstrate that the redox-capacitor can enlist the capabilities of electrochemistry to generate rapid and sensitive signatures of biologically-relevant chemical activities (i.e., redox-cycling). Published by Elsevier B.V.

  5. Reduced glutathione as a persistence indicator of alien plants of the Amelancheir family

    Directory of Open Access Journals (Sweden)

    L. G. Dolgova

    2009-04-01

    Full Text Available It was proved that glutathione is an important indicator of the vegetation condition and persistence. According to the amount of glutathione the studied mespilus species are adapted to the environmental conditions. Increase of the glutathione amount is caused by some abiotic factors, e.g. temperature. Some differences of the glutathione content may be explained by the plants species patterns.

  6. 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.

  7. 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.

  8. The Deep Thioredoxome in Chlamydomonas reinhardtii: New Insights into Redox Regulation.

    Science.gov (United States)

    Pérez-Pérez, María Esther; Mauriès, Adeline; Maes, Alexandre; Tourasse, Nicolas J; Hamon, Marion; Lemaire, Stéphane D; Marchand, Christophe H

    2017-08-07

    Thiol-based redox post-translational modifications have emerged as important mechanisms of signaling and regulation in all organisms, and thioredoxin plays a key role by controlling the thiol-disulfide status of target proteins. Recent redox proteomic studies revealed hundreds of proteins regulated by glutathionylation and nitrosylation in the unicellular green alga Chlamydomonas reinhardtii, while much less is known about the thioredoxin interactome in this organism. By combining qualitative and quantitative proteomic analyses, we have comprehensively investigated the Chlamydomonas thioredoxome and 1188 targets have been identified. They participate in a wide range of metabolic pathways and cellular processes. This study broadens not only the redox regulation to new enzymes involved in well-known thioredoxin-regulated metabolic pathways but also sheds light on cellular processes for which data supporting redox regulation are scarce (aromatic amino acid biosynthesis, nuclear transport, etc). Moreover, we characterized 1052 thioredoxin-dependent regulatory sites and showed that these data constitute a valuable resource for future functional studies in Chlamydomonas. By comparing this thioredoxome with proteomic data for glutathionylation and nitrosylation at the protein and cysteine levels, this work confirms the existence of a complex redox regulation network in Chlamydomonas and provides evidence of a tremendous selectivity of redox post-translational modifications for specific cysteine residues. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Characterization of redox conditions in pollution plumes

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Bjerg, Poul Løgstrup; Banwart, Steven A.

    2000-01-01

    Evalution of redox conditions in groundwater pollution plumes is often a prerequisite for understanding the behviour of the pollutants in the plume and for selecting remediation approaches. Measuring of redox conditions in pollution plumes is, however, a fairly recent issue and yet relative few...

  11. Redox properties of small semiconductor particles

    International Nuclear Information System (INIS)

    Liver, N.; Nitzan, A.

    1992-01-01

    The size dependence of electrical and thermodynamic quantities of intermediate-sized semiconductor particles in an electrolyte solution with a given redox pair are studied. The equilibrium constant for this system is then derived based on the relationship of the electrolytic redox components to the size, charges, and concentration of the semiconductor particles. 25 refs., 9 figs., 1 tab

  12. Characterization of redox proteins using electrochemical methods

    NARCIS (Netherlands)

    Verhagen, M.

    1995-01-01

    The use of electrochemical techniques in combination with proteins started approximately a decade ago and has since then developed into a powerfull technique for the study of small redox proteins. In addition to the determination of redox potentials, electrochemistry can be used to obtain

  13. 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.

  14. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis.

    Science.gov (United States)

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

    1991-07-27

    Idiopathic pulmonary fibrosis (IPF) is characterised by alveolar inflammation, exaggerated release of oxidants, and subnormal concentrations of the antioxidant glutathione in respiratory epithelial lining fluid (ELF). Glutathione (600 mg twice daily for 3 days) was given by aerosol to 10 patients with IPF. Total ELF glutathione rose transiently, ELF oxidised glutathione concentrations increased, and there was a decrease in spontaneous superoxide anion release by alveolar macrophages. Thus, glutathione by aerosol could be a means of reversing the oxidant-antioxidant imbalance in IPF.

  15. 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.

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

    Science.gov (United States)

    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.

  17. Engineered Proteins: Redox Properties and Their Applications

    Science.gov (United States)

    Prabhulkar, Shradha; Tian, Hui; Wang, Xiaotang; Zhu, Jun-Jie

    2012-01-01

    Abstract Oxidoreductases and metalloproteins, representing more than one third of all known proteins, serve as significant catalysts for numerous biological processes that involve electron transfers such as photosynthesis, respiration, metabolism, and molecular signaling. The functional properties of the oxidoreductases/metalloproteins are determined by the nature of their redox centers. Protein engineering is a powerful approach that is used to incorporate biological and abiological redox cofactors as well as novel enzymes and redox proteins with predictable structures and desirable functions for important biological and chemical applications. The methods of protein engineering, mainly rational design, directed evolution, protein surface modifications, and domain shuffling, have allowed the creation and study of a number of redox proteins. This review presents a selection of engineered redox proteins achieved through these methods, resulting in a manipulation in redox potentials, an increase in electron-transfer efficiency, and an expansion of native proteins by de novo design. Such engineered/modified redox proteins with desired properties have led to a broad spectrum of practical applications, ranging from biosensors, biofuel cells, to pharmaceuticals and hybrid catalysis. Glucose biosensors are one of the most successful products in enzyme electrochemistry, with reconstituted glucose oxidase achieving effective electrical communication with the sensor electrode; direct electron-transfer-type biofuel cells are developed to avoid thermodynamic loss and mediator leakage; and fusion proteins of P450s and redox partners make the biocatalytic generation of drug metabolites possible. In summary, this review includes the properties and applications of the engineered redox proteins as well as their significance and great potential in the exploration of bioelectrochemical sensing devices. Antioxid. Redox Signal. 17, 1796–1822. PMID:22435347

  18. 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®.

  19. 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.

  20. A Protocol for Electrochemical Evaluations and State of Charge Diagnostics of a Symmetric Organic Redox Flow Battery

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Wentao; Vemuri, Rama S.; Hu, Dehong; Yang, Zheng; Wei, Xiaoliang

    2017-01-01

    Redox flow batteries have been considered as one of the most promising stationary energy storage solutions for improving the reliability of the power grid and deployment of renewable energy technologies. Among the many flow battery chemistries, nonaqueous flow batteries have the potential to achieve high energy density because of the broad voltage windows of nonaqueous electrolytes. However, significant technical hurdles exist currently limiting nonaqueous flow batteries to demonstrate their full potential, such as low redox concentrations, low operating currents, under-explored battery status monitoring, etc. In an attempt to address these limitations, we report a nonaqueous flow battery based on a highly soluble, redox-active organic nitronyl nitroxide radical compound, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). This redox materials exhibits an ambipolar electrochemical property with two reversible redox pairs that are moderately separated by a voltage gap of ~1.7 V. Therefore, PTIO can serve as both anolyte and catholyte redox materials to form a symmetric flow battery chemistry, which affords the advantages such as high effective redox concentrations and low irreversible redox material crossover. The PTIO flow battery shows decent electrochemical cyclability under cyclic voltammetry and flow cell conditions; an improved redox concentration of 0.5 M PTIO and operational current density of 20 mA cm-2 were achieved in flow cell tests. Moreover, we show that Fourier transform infrared (FTIR) spectroscopy could measure the PTIO concentrations during the PTIO flow battery cycling and offer reasonably accurate detection of the battery state of charge (SOC) as cross-validated by electron spin resonance measurements. This study suggests FTIR can be used as a reliable online SOC sensor to monitor flow battery status and ensure battery operations stringently in a safe SOC range.

  1. Ruthenium nanocatalysis on redox reactions.

    Science.gov (United States)

    Veerakumar, Pitchaimani; Ramdass, Arumugam; Rajagopal, Seenivasan

    2013-07-01

    Nanoparticles have generated intense interest over the past 20 years due to their high potential applications in different areas such as catalysis, sensors, nanoscale electronics, fuel and solar cells and optoelectronics. As the large fractions of metal atoms are exposed to the surface, the use of metal nanoparticles as nanocatalysts allows mild reaction conditions and high catalytic efficiency in a large number of chemical transformations. They have emerged as sustainable heterogeneous catalysts and catalyst supports alternative to conventional materials. This review focuses on the synthesis, characterization and catalytic role of ruthenium nanoparticles (RuNPs) on the redox reactions of heteroatom containing organic compounds with the green reagent H2O2, a field that has attracted immense interest among the chemical, materials and industrial communities. We intend to present a broad overview of Ru nanocatalysts for redox reactions with an emphasis on their performance, stability and reusability. The growth in the chemistry of organic sulfoxides and N-oxides during last decade was due to their importance as synthetic intermediates for the production of a wide range of chemically and biologically active molecules. Thus design of efficient methods for the synthesis of sulfoxides and N-oxides becomes important. This review concentrates on the catalysis of RuNPs on the H2O2 oxidation of organic sulfides to sulfoxides and amines to N-oxides. The deoxygenation reactions of sulfoxides to sulfides and reduction of nitro compounds to amines are fundamental reactions in both chemistry and biology. Here, we also highlight the catalysis of metal nanoparticles on the deoxygenation of sulfoxides and sulfones and reduction of nitro compounds with particular emphasis on the mechanistic aspects.

  2. 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.

  3. The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

    Directory of Open Access Journals (Sweden)

    Megan M. Cartwright

    2016-10-01

    Full Text Available Inhalation of multiwalled carbon nanotubes (MWCNTs during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH. Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25 µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate (Gclm heterozygous and severe (Gclm null GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.

  4. 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).

  5. Targeting of the Glutathione, Thioredoxin, and Nrf2 Antioxidant Systems in Head and Neck Cancer.

    Science.gov (United States)

    Roh, Jong-Lyel; Jang, Hyejin; Kim, Eun Hye; Shin, Daiha

    2017-07-10

    The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells. Dual silencing of the genes for GCLM and TrxR1 induced GSH depletion, Trx activity inhibition, and ROS accumulation, synergistically killing HNC cells. Inhibition of the GSH and Trx systems resulted in activation of the Nrf2-antioxidant response element (ARE) pathway, which may result in suboptimal GSH and Trx inhibition where HNC is resistant. Genetic inhibition of Nrf2 and/or HO-1 or trigonelline enhanced growth suppression, ROS accumulation, and cell death from GSH and Trx inhibition. The in vivo effects of GSH, Trx, and Nrf2 system inhibition were confirmed in a mouse HNC xenograft model by achieving growth inhibition >60% compared with those of control. Innovations: This study is the first to show that triple inhibition of GSH, Trx, and Nrf2 pathways could be an effective method to overcome the resistance of HNC. Inhibition of the Nrf2-ARE pathway in addition to dual inhibition of the GSH and Trx antioxidant systems can effectively eliminate resistant HNC. Antioxid. Redox Signal. 27, 106-114.

  6. 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

  7. 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)

  8. 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.

  9. 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.

  10. Albumin-gold-glutathione is a probable auranofin metabolite

    International Nuclear Information System (INIS)

    Shaw, C.F. III; Coffer, M.; Isab, A.A.

    1989-01-01

    The newly licensed gold drug, auranofin ((2,3,4,6-tetra-O-acetyl-β-1-D-gluco-pyranosato-S-)triethylphoshine-gold(I)) crosses cell membranes and enters cells which are inaccessible to parenteral gold drugs. In vivo, the triethylphosphine ligand and gold of auranofin, but not the thio-sugar moiety, accumulate in and subsequently efflux from red blood cells (RBCs). Extracellular albumin increases in the extent of gold efflux and acts as a gold binding site. The rate of efflux is first-order in RBC gold concentration. Studies using RBCs in which labelled [ 14 C]-glutathione is generated in situ incorporation of [ 14 C]- glycine demonstrate that glutathione also effluxes from the RBCs and forms a gold-glutathione-albumin complex. This may be the immunopharmacologically active complex

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

    NARCIS (Netherlands)

    Tillmann, Anna T.; Strijbis, Karin; Cameron, Gary; Radmaneshfar, Elahe; Thiel, Marco; Munro, Carol A.; Maccallum, Donna M.; Distel, Ben; Gow, Neil A. R.; Brown, Alistair J. P.

    2015-01-01

    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

  12. Redox kinetics and mechanism in silicate melts

    International Nuclear Information System (INIS)

    Cochain, B.

    2009-12-01

    This work contributes to better understand iron redox reactions and mechanisms in silicate melts. It was conducted on compositions in both Na 2 O-B 2 O 3 -SiO 2 -FeO and Na 2 O-Al 2 O 3 -SiO 2 -FeO systems. The influence of boron-sodium and aluminum-sodium substitutions and iron content on properties and structure of glasses and on the iron redox kinetics has been studied by Raman, Moessbauer and XANES spectroscopies at the B and Fe K-edges. In borosilicate glasses, an increase in iron content or in the Fe 3+ /ΣFe redox state implies a structural rearrangement of the BO 4 species in the glass network whereas the BO 3 and BO 4 relative proportions remain nearly constant. In all studied glasses and melts, Fe 3+ is a network former in tetrahedral coordination, unless for aluminosilicates of ratio Al/Na≥1 where Fe 3+ is a network modifier in five-fold coordination. Near Tg, diffusion of network modifying cations controls the iron redox kinetics along with a flux of electron holes. At liquidus temperatures, oxygen diffusion is considered to be the mechanism that governs redox reactions. This study shows the role played by the silicate network polymerization on the redox kinetics. In borosilicate melts, iron redox kinetics depends on the boron speciation between BO 3 and BO 4 that depends itself on the sodium content. Furthermore, an increase in the network-former/network-modifier ratio implies a decrease in oxygen diffusion that results in a slowing down of the redox kinetics. The obtained results allow a description of the iron redox kinetics for more complex compositions as natural lavas or nuclear waste model glasses. (author)

  13. 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.

  14. 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.

  15. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 know