Nitric oxide and carbon monoxide diffusing capacity after a 1-h oxygen dive to 9 m of sea water

NARCIS (Netherlands)

van Ooij, P. J. A. M.; van Hulst, R. A.; Houtkooper, A.; Sterk, P. J.

2014-01-01

To prevent extensive pulmonary lesions in submerged oxygen divers lung function like the forced vital capacity (FVC) or the diffusing capacity for carbon monoxide (DL,co) are used to monitor pulmonary oxygen toxicity (POT). As the diffusing capacity for nitric oxide (DL,no) measures more accurately

Production of nitric oxide using a microwave plasma torch and its application to fungal cell differentiation

International Nuclear Information System (INIS)

Na, Young Ho; Kang, Min-Ho; Cho, Guang Sup; Choi, Eun Ha; Park, Gyungsoon; Uhm, Han Sup; Kumar, Naresh

2015-01-01

The generation of nitric oxide by a microwave plasma torch is proposed for its application to cell differentiation. A microwave plasma torch was developed based on basic kinetic theory. The analytical theory indicates that nitric oxide density is nearly proportional to oxygen molecular density and that the high-temperature flame is an effective means of generating nitric oxide. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimeters per minute. The apparent length of the torch flame increases as the oxygen input increases. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the mole fraction of oxygen gas, and the microwave power. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to a model microbial cell (Neurospora crassa: non-pathogenic fungus). Germination and hyphal differentiation of fungal cells were not dramatically changed but there was a significant increase in spore formation after treatment with nitric oxide. In addition, the expression level of a sporulation related gene acon-3 was significantly elevated after 24 h upon nitric oxide treatment. Increase in the level of nitric oxide, nitrite and nitrate in water after nitric oxide treatment seems to be responsible for activation of fungal sporulation. Our results suggest that nitric oxide generated by plasma can be used as a possible activator of cell differentiation and development. (paper)

Electrochemical Reduction of Oxygen and Nitric Oxide at Low Temperature on La1−xSrxCoO3−delta Cathodes

DEFF Research Database (Denmark)

Kammer Hansen, Kent

2010-01-01

Six La1-xSrxCoO3- (x= 0, 0.05, 0.15, 0.25, 0.35, 0.50) perovskites were synthesised and characterised by powder XRD and cyclic voltammetry on cone-shaped electrodes in either air or nitric oxide in argon at 200, 300 and 400oC. At 200oC the current densities in air was highest for the strontium.......50Sr0.50CoO3-, in both air and the nitric oxide containing atmosphere. This was attributed to a rate limiting chemical step (i.e. dissociation of oxygen or nitric oxide) in the reaction sequence....

Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a PET study with nitric oxide and cyclooxygenase inhibition

DEFF Research Database (Denmark)

Heinonen, Ilkka; Saltin, Bengt; Kemppainen, Jukka

2011-01-01

The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed 3 five min bouts of light knee-extensor exercise. Skeletal...... muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H(2)O(15) and (15)O(2) during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of L-NMMA and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of L...

Effect of systemic nitric oxide synthase inhibition on optic disc oxygen partial pressure in normoxia and in hypercapnia.

Science.gov (United States)

Petropoulos, Ioannis K; Pournaras, Jean-Antoine C; Stangos, Alexandros N; Pournaras, Constantin J

2009-01-01

To investigate the effect of systemic nitric oxide synthase (NOS) inhibition on optic disc oxygen partial pressure (PO(2)) in normoxia and hypercapnia. Intervascular optic disc PO(2) was measured in 12 anesthetized minipigs by using oxygen-sensitive microelectrodes placed 0.1), despite a 21% increase of mean arterial pressure. Optic disc PO(2) increase under hypercapnia was blunted after L-NAME injection (DeltaPO(2) = 0.6 +/- 1.1 mm Hg; 3%; P > 0.1), and this effect was reversible by L-arginine. Moreover, L-NAME reduced the response to carbogen by 29% (DeltaPO(2) = 9.1 +/- 4.4 mm Hg; 49%; P = 0.01 versus before L-NAME). The response to hyperoxia was not affected. Whereas systemic NOS inhibition did not affect optic disc PO(2) in normoxia, a blunting effect was noted on the CO(2)-induced optic disc PO(2) increase. Nitric oxide appears to mediate the hypercapnic optic disc PO(2) increase.

[Ultrasound induced the formation of nitric oxide and nitrosonium ions in water and aqueous solutions].

Science.gov (United States)

Stepuro, I I; Adamchuk, R I; Stepuro, V I

2004-01-01

Nitric oxide, nitrosonium ions, nitrites, and nitrates are formed in water saturated with air under the action of ultrasound. Nitrosonium ions react with water and hydrogen peroxide to form nitrites and nitrates in sonicated solution, correspondingly. Nitric oxide is practically completely released from sonicated water into the atmosphere and reacts with air oxygen, forming NOx compounds. The oxidation of nitric oxide in aqueous medium by hydroxyl radicals and dissolved oxygen is a minor route of the formation of nitrites and nitrates in ultrasonic field.

Flavonoids as scavengers of nitric oxide radical.

NARCIS (Netherlands)

van Acker, S.A.B.E.; Tromp, M.N.J.L.; Haenen, G.R.M.M.; van der Vijgh, W.J.F.; Bast, A.

1995-01-01

Flavonoids are a group of naturally occurring compounds used, e.g., in the treatment of vascular endothelial damage. They are known to be excellent scavengers of oxygen free radicals. Since the nitric oxide radical (

Nitric oxide: a physiologic messenger.

Science.gov (United States)

Lowenstein, C J; Dinerman, J L; Snyder, S H

1994-02-01

To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

The effect of inhaled nitric oxide in acute respiratory distress syndrome in children and adults

DEFF Research Database (Denmark)

Karam, O; Gebistorf, F; Wetterslev, J

2017-01-01

on mortality in adults and children with acute respiratory distress syndrome. We included all randomised, controlled trials, irrespective of date of publication, blinding status, outcomes reported or language. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity......Acute respiratory distress syndrome is associated with high mortality and morbidity. Inhaled nitric oxide has been used to improve oxygenation but its role remains controversial. Our primary objective in this systematic review was to examine the effects of inhaled nitric oxide administration......% CI) 1.59 (1.17-2.16)) with inhaled nitric oxide. In conclusion, there is insufficient evidence to support inhaled nitric oxide in any category of critically ill patients with acute respiratory distress syndrome despite a transient improvement in oxygenation, since mortality is not reduced and it may...

Normalization of hemoglobin-based oxygen carrier-201 induced vasoconstriction: targeting nitric oxide and endothelin.

Science.gov (United States)

Taverne, Yannick J; de Wijs-Meijler, Daphne; Te Lintel Hekkert, Maaike; Moon-Massat, Paula F; Dubé, Gregory P; Duncker, Dirk J; Merkus, Daphne

2017-05-01

Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore, we aimed to 1 ) determine the possibility of counteracting HBOC-201-induced pressor effects with either adenosine (ADO) or nitroglycerin (NTG); 2 ) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS), and endothelin (ET) in mediating the observed vasoconstriction; and 3 ) compare these effects in resting and exercising swine. Chronically instrumented swine were studied at rest and during exercise after administration of HBOC-201 alone or in combination with ADO. The role of NO was assessed by supplementation with NTG or administration of the eNOS inhibitor N ω -nitro-l-arginine. Alternative vasoactive pathways were investigated via intravenous administration of the ET A /ET B receptor blocker tezosentan or a mixture of ROS scavengers. The systemic and to a lesser extent the pulmonary pressor effects of HBOC-201 could be counteracted by ADO; however, dosage titration was very important to avoid systemic hypotension. Similarly, supplementation of NO with NTG negated the pressor effects but also required titration of the dose. The pressor response to HBOC-201 was reduced after eNOS inhibition and abolished by simultaneous ET A /ET B receptor blockade, while ROS scavenging had no effect. In conclusion, the pressor response to HBOC-201 is mediated by vasoconstriction due to NO scavenging and production of ET. Further research should explore the effect of longer-acting ET receptor blockers to counteract the side effect of hemoglobin-based oxygen carriers. NEW & NOTEWORTHY Hemoglobin-based oxygen carrier (HBOC)-201 can disrupt hemodynamic homeostasis, mimicking some aspects of endothelial dysfunction, resulting in elevated systemic and pulmonary blood

A plasma needle generates nitric oxide

International Nuclear Information System (INIS)

Stoffels, E; Gonzalvo, Y Aranda; Whitmore, T D; Seymour, D L; Rees, J A

2006-01-01

Generation of nitric oxide (NO) by a plasma needle is studied by means of mass spectrometry. The plasma needle is an atmospheric glow generated by a radio-frequency excitation in a mixture of helium and air. This source is used for the treatment of living tissues, and nitric oxide may be one of the most important active agents in plasma therapy. Efficient NO generation is of particular importance in the treatment of cardiovascular diseases. Mass spectrometric measurements have been performed under various plasma conditions; gas composition in the plasma and conversion of feed gases (nitrogen and oxygen) into other species has been studied. Up to 30% of the N 2 and O 2 input is consumed in the discharge, and NO has been identified as the main conversion product

Nitric oxide formation from the reaction of nitrite with carp and rabbit hemoglobin at intermediate oxygen saturations

DEFF Research Database (Denmark)

Jensen, Frank Bo

2008-01-01

The nitrite reductase activity of deoxyhemoglobin has received much recent interest because the nitric oxide produced in this reaction may participate in blood flow regulation during hypoxia. The present study used spectral deconvolution to characterize the reaction of nitrite with carp and rabbit...... hemoglobin at different constant oxygen tensions that generate the full range of physiological relevant oxygen saturations. Carp is a hypoxia-tolerant species with very high hemoglobin oxygen affinity, and the high R-state character and low redox potential of the hemoglobin is hypothesized to promote...... NO generation from nitrite. The reaction of nitrite with deoxyhemoglobin leads to a 1 : 1 formation of nitrosylhemoglobin and methemoglobin in both species. At intermediate oxygen saturations, the reaction with deoxyhemoglobin is clearly favored over that with oxyhemoglobin, and the oxyhemoglobin reaction...

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

Science.gov (United States)

Edwards, Aurélie; Layton, Anita T.

2015-01-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. PMID:25651567

Processes regulating nitric oxide emissions from soils

DEFF Research Database (Denmark)

Pilegaard, Kim

2013-01-01

, the net result is complex and dependent on several factors such as nitrogen availability, organic matter content, oxygen status, soil moisture, pH and temperature. This paper reviews recent knowledge on processes forming NO in soils and the factors controlling its emission to the atmosphere. Schemes......Nitric oxide (NO) is a reactive gas that plays an important role in atmospheric chemistry by influencing the production and destruction of ozone and thereby the oxidizing capacity of the atmosphere. NO also contributes by its oxidation products to the formation of acid rain. The major sources...

Experience with inhaled nitric oxide therapy in hypoxic respiratory failure of the newborn.

Science.gov (United States)

Sehgal, Arvind; Callander, Ian; Stack, Jacqueline; Momsen, Tracey; Sterling-Levis, Katy

2005-01-01

Respiratory diseases are the commonest cause of morbidity and mortality in newborns. Inhaled nitric oxide (iNO) has been shown to be effective in the management of persistent pulmonory hypertension of newborn (PPHN). To retrospectively analyse data to determine the effectiveness of inhaled nitric oxide (iNO) in the management of newborns with PPHN in terms of survival and changes in oxygenation status. Neo-natal data since inception of iNO therapy at the unit (past six years) was reviewed. Pertinent demographic and clinical information was collected from medical records of newborns that received inhaled nitric oxide therapy during their stay. Details of underlying illnesses, other therapeutic modalities, arterial blood gas, ventilatory and nitric oxide parameters were assessed and analysed to ascertain efficacy of iNO. A total of 36 babies (gestational age ranging from 24-41 weeks) received iNO during this period; two were excluded from final analysis. Overall survival rate was 80 percent. There was a statistically significant increase in systemic oxygenation (PaO2) from 41.1 +/- 2.1 mmHg to 128.5 +/- 13.2 mmHg and a decline in oxygenation index (OI) from 49.4 +/- 5.9 to 17.3 +/- 2.5, when assessed after four hours (P < 0.001). Mean duration of iNO therapy was 63 +/- 7.3 hours and the maximum methaemoglobin levels were noted to be 2.1 percent. Inhaled nitric oxide appears to be an effective rescue therapy for the management of PPHN associated with hypoxic respiratory failure. It is safe and well tolerated with no evidence of clinical or biochemical side effects.

Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance.

Science.gov (United States)

Chakraborty, Jayashree B; Mahato, Sanjit K; Joshi, Kalpana; Shinde, Vaibhav; Rakshit, Srabanti; Biswas, Nabendu; Choudhury Mukherjee, Indrani; Mandal, Labanya; Ganguly, Dipyaman; Chowdhury, Avik A; Chaudhuri, Jaydeep; Paul, Kausik; Pal, Bikas C; Vinayagam, Jayaraman; Pal, Churala; Manna, Anirban; Jaisankar, Parasuraman; Chaudhuri, Utpal; Konar, Aditya; Roy, Siddhartha; Bandyopadhyay, Santu

2012-01-01

Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr-Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria-derived reactive oxygen species. Reactive oxygen species-dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase-mediated nitric oxide generation. This causes loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3 and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH analogue was also effective in vivo in SCID mice against grafts expressing the T315I mutation, although to a lesser extent than grafts expressing wild type Bcr-Abl, without showing significant bodyweight loss. Our data describe the role of JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti-CML activity of HCH and this molecule merits further testing in pre-clinical and clinical settings. © 2011 Japanese Cancer Association.

Physiological Levels of Nitric Oxide Diminish Mitochondrial Superoxide. Potential Role of Mitochondrial Dinitrosyl Iron Complexes and Nitrosothiols

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Sergey I. Dikalov

2017-11-01

Full Text Available Mitochondria are the major source of superoxide radicals and superoxide overproduction contributes to cardiovascular diseases and metabolic disorders. Endothelial dysfunction and diminished nitric oxide levels are early steps in the development of these pathological conditions. It is known that physiological production of nitric oxide reduces oxidative stress and inflammation, however, the precise mechanism of “antioxidant” effect of nitric oxide is not clear. In this work we tested the hypothesis that physiological levels of nitric oxide diminish mitochondrial superoxide production without inhibition of mitochondrial respiration. In order to test this hypothesis we analyzed effect of low physiological fluxes of nitric oxide (20 nM/min on superoxide and hydrogen peroxide production by ESR spin probes and Amplex Red in isolated rat brain mitochondria. Indeed, low levels of nitric oxide substantially attenuated both basal and antimycin A-stimulated production of reactive oxygen species in the presence of succinate or glutamate/malate as mitochondrial substrates. Furthermore, slow releasing NO donor DPTA-NONOate (100 μM did not change oxygen consumption in State 4 and State 3. However, the NO-donor strongly inhibited oxygen consumption in the presence of uncoupling agent CCCP, which is likely associated with inhibition of the over-reduced complex IV in uncoupled mitochondria. We have examined accumulation of dinitrosyl iron complexes and nitrosothiols in mitochondria treated with fast-releasing NO donor MAHMA NONOate (10 μM for 30 min until complete release of NO. Following treatment with NO donor, mitochondria were frozen for direct detection of dinitrosyl iron complexes using Electron Spin Resonance (ESR while accumulation of nitrosothiols was measured by ferrous-N-Methyl-D-glucamine dithiocarbamate complex, Fe(MGD2, in lysed mitochondria. Treatment of mitochondria with NO-donor gave rise to ESR signal of dinitrosyl iron complexes while ESR

[Techniques and complementary techniques. Complementary treatments: nitric oxide, prone positioning and surfactant].

Science.gov (United States)

Martos Sánchez, I; Vázquez Martínez, J L; Otheo de Tejada, E; Ros, P

2003-11-01

The management of hypoxic respiratory failure is based on oxygen delivery and ventilatory support with lung-protective ventilation strategies. Better understanding of acute lung injury have led to new therapeutic approaches that can modify the outcome of these patients. These adjunctive oxygenation strategies include inhaled nitric oxide and surfactant delivery, and the use of prone positioning. Nitric oxide is a selective pulmonary vasodilator that when inhaled, improves oxygenation in clinical situations such as persistent pulmonary hypertension of the newborn, pulmonary hypertension associated with congenital heart disease, and acute respiratory distress syndrome (ARDS). When applied early in ARDS, prone positioning improves distribution of ventilation and reduces the intrapulmonary shunt. The surfactant has dramatically decreased mortality caused by hyaline membrane disease in premature newborns, although the results have been less successful in ARDS. Greater experience is required to determine whether the combination of these treatments will improve the prognosis of these patients.

Radiation, nitric oxide and cellular death

International Nuclear Information System (INIS)

Dubner, D.; Perez, M.R. Del; Michelin, S.C.; Gisone, P.A.

1997-01-01

The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

Isoxazole derivatives as new nitric oxide elicitors in plants

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Anca Oancea

2017-04-01

Full Text Available Several 3,5-disubstituted isoxazoles were obtained in good yields by regiospecific 1,3-dipolar cycloaddition reactions between aromatic nitrile oxides, generated in situ from the corresponding hydroxyimidoyl chlorides, with non-symmetrical activated alkynes in the presence of catalytic amounts of copper(I iodide. Effects of 3,5-disubstituted isoxazoles on nitric oxide and reactive oxygen species generation in Arabidopsis tissues was studied using specific diaminofluoresceine dyes as fluorescence indicators.

The effect of lipid peroxidation products on reactive oxygen species formation and nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages

Czech Academy of Sciences Publication Activity Database

Ambrožová, Gabriela; Pekarová, Michaela; Lojek, Antonín

2011-01-01

Roč. 25, č. 1 (2011), s. 145-152 ISSN 0887-2333 R&D Projects: GA MŠk(CZ) OC08058; GA ČR(CZ) GA524/08/1753 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : lipid peroxidation products * reactive oxygen species * nitric oxide Subject RIV: BO - Biophysics Impact factor: 2.775, year: 2011

Reduction of nitric oxide by arc vaporized carbons (AVC)

Energy Technology Data Exchange (ETDEWEB)

Tsang, S C; Chen, Y K; Green, M L.H. [The Catalysis Centre, Inorganic Chemistry Laboratory, University of Oxford, Oxford (United Kingdom)

1996-07-04

The reduction of nitric oxide by arc vaporized carbons (AVC) including the compound C{sub 6}0, fullerene soot and carbon nanotubes, giving dinitrogen and carbon oxides has been studied. It is found that the AVC carbons are more active towards oxidation by NO than by oxygen gas at low temperatures (300-400C). In contrast, conventional carbons such as graphite and microporous carbons are more readily oxidised by oxygen than by NO. The addition of copper salts and to a lesser extent, cobalt salts, to fullerene soot substantially promote NO reduction. The high intrinsic activity for NO reduction by AVC carbons compared to graphitic carbons is attributed to the presence of five membered carbon rings in the AVC carbons

Lithium-Vanadium bronzes as model catalysts for the selective reduction of nitric oxide

NARCIS (Netherlands)

Bosch, H.; Bongers, Annemie; Enoch, Gert; Snel, Ruud; Ross, Julian R.H.

1989-01-01

The effect of alkali metals on the selective reduction of nitric oxide with ammonia has been studied on bulk iron oxide and bulk vanadium oxide. The influence of additions of LiOH, NaOH and KOH on the activity was screened by pulse experiments carried out in the absence of gaseous oxygen; FTIR

Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide-Dependent Tolerance Pathway

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Kim Vriens

2017-01-01

Full Text Available Amphotericin B (AmB induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB-induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB’s fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L-NAME was used to interfere with nitric oxide radical production. L-NAME increased and accelerated AmB-induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S-nitrosoglutathione inhibited AmB’s action. Hence, superoxide radicals were important for AmB’s fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L-NAME, pointing to the potential of AmB-L-NAME combination therapy to treat fungal infections.

The effect of lipid peroxidation products on reactive oxygen species formation and nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages.

Science.gov (United States)

Ambrozova, Gabriela; Pekarova, Michaela; Lojek, Antonin

2011-02-01

Lipid peroxidation induced by oxidants leads to the formation of highly reactive metabolites. These can affect various immune functions, including reactive oxygen species (ROS) and nitric oxide (NO) production. The aim of the present study was to investigate the effects of lipid peroxidation products (LPPs) - acrolein, 4-hydroxynonenal, and malondialdehyde - on ROS and NO production in RAW 264.7 macrophages and to compare these effects with the cytotoxic properties of LPPs. Macrophages were stimulated with lipopolysaccharide (0.1 μg/ml) and treated with selected LPPs (concentration range: 0.1-100 μM). ATP test, luminol-enhanced chemiluminescence, Griess reaction, Western blotting analysis, amperometric and total peroxyl radical-trapping antioxidant parameter assay were used for determining the LPPs cytotoxicity, ROS and NO production, inducible nitric oxide synthase expression, NO scavenging, and antioxidant properties of LPPs, respectively. Our study shows that the cytotoxic action of acrolein and 4-hydroxynonenal works in a dose- and time-dependent manner. Further, our results imply that acrolein, 4-hydroxynonenal, and malondialdehyde can inhibit, to a different degree, ROS and NO production in stimulated macrophages, partially independently of their toxic effect. Also, changes in enzymatic pathways (especially NADPH-oxidase and nitric oxide synthase inhibition) and NO scavenging properties are included in the downregulation of reactive species formation. Copyright © 2010 Elsevier Ltd. All rights reserved.

The role of nitrite in nitric oxide homeostasis

DEFF Research Database (Denmark)

Jensen, Frank Bo

2009-01-01

Nitrite is endogenously produced as an oxidative metabolite of nitric oxide, but it also functions as a NO donor that can be activated by a number of cellular proteins under hypoxic conditions. This article discusses the physiological role of nitrite and nitrite-derived NO in blood flow regulation...... mechanisms. Nitrite reduction to NO provides cytoprotection in tissues during ischemia-reperfusion events by inhibiting mitochondrial respiration and limiting reactive oxygen species. It is argued that the study of hypoxia-tolerant lower vertebrates and diving mammals may help evaluate mechanisms and a full...

Therapeutic strategies to address neuronal nitric oxide synthase deficiency and the loss of nitric oxide bioavailability in Duchenne Muscular Dystrophy.

Science.gov (United States)

Timpani, Cara A; Hayes, Alan; Rybalka, Emma

2017-05-25

Duchenne Muscular Dystrophy is a rare and fatal neuromuscular disease in which the absence of dystrophin from the muscle membrane induces a secondary loss of neuronal nitric oxide synthase and the muscles capacity for endogenous nitric oxide synthesis. Since nitric oxide is a potent regulator of skeletal muscle metabolism, mass, function and regeneration, the loss of nitric oxide bioavailability is likely a key contributor to the chronic pathological wasting evident in Duchenne Muscular Dystrophy. As such, various therapeutic interventions to re-establish either the neuronal nitric oxide synthase protein deficit or the consequential loss of nitric oxide synthesis and bioavailability have been investigated in both animal models of Duchenne Muscular Dystrophy and in human clinical trials. Notably, the efficacy of these interventions are varied and not always translatable from animal model to human patients, highlighting a complex interplay of factors which determine the downstream modulatory effects of nitric oxide. We review these studies herein.

A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

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Nevzat Selim Gokay

2016-01-01

Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

Nitric oxide in the rat cerebellum after hypoxia/ischemia.

Science.gov (United States)

Rodrigo, José; Fernández, Ana Patricia; Alonso, David; Serrano, Julia; Fernández-Vizarra, Paula; Martínez-Murillo, Ricardo; Bentura, María Luisa; Martinez, Alfredo

2004-01-01

Nitric oxide is a regulatory biological substance and an important intracellular messenger that acts as a specific mediator of various neuropathological disorders. In mammals and invertebrates, nitric oxide is synthesized from L-arginine in the central and peripheral neural structures by the endothelial, neuronal and inducible enzymatic isoforms of nitric oxide synthase. Nitric oxide may affect the function of various neurotransmitter-specific systems, and is involved in neuromodulation, reproductive function, immune response, and regulation of the cerebral blood circulation. This makes nitric oxide the main candidate in brain responses to brain ischemia/hypoxia. The cerebellum has been reported to be the area of the brain that has the highest nitric oxide synthase activity and the highest concentration of glutamate and aspartate. By glutamate receptors and physiological action of nitric oxide, cyclic guanisine-5'-monophosphate may be rapidly increased. The cerebellum significantly differs with respect to ischemia and hypoxia, this response being directly related to the duration and intensity of the injury. The cerebellum could cover the eventual need for nitric oxide during the hypoxia, boosting the nitric oxide synthase activity, but overall ischemia would require de novo protein synthesis, activating the inducible nitric oxide synthase to cope with the new situation. The specific inhibitors of nitric oxide synthesis show neuroprotective effects.

Nitric oxide turnover in permeable river sediment

DEFF Research Database (Denmark)

Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M

2014-01-01

We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed......-nitroso-N-acetylpenicillamine (SNAP) (1) confirmed denitrification as the main NO consumption pathway, with N2O as its major product, (2) showed that denitrification combines one free NO molecule with one NO molecule formed from nitrite to produce N2O, and (3) suggested that NO inhibits N2O reduction....

Inhaled nitric oxide and high concentrations of oxygen in pediatrics patients with congenital cardiopathy and pulmonary hypertension: report of five cases

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Werther Brunow de Carvalho

Full Text Available Five patients with ages ranging from 6 months to 3 years were analyzed. All received inhaled nitric oxide (NO - 20 parts per million (ppm and oxygen (0(2 - at a concentration of 90-95% by means of an oxygen hood. Mean Pulmonary Artery Pressure (MPAP, Mean Aortic Pressure (MAoP, Pulmonary Vascular Resistance (PVR and Systemic Vascular Resistance (SVR were measured and the calculation of their relationship to pulmonary/systemic flow (Qp/Qs was performed by the catheterization' of the femoral artery vein. Three patients presented reduction in PVR and increase in Qp/Qs. There were no systemic alterations or any side effect from using NO.

Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging

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Gordish, Kevin L.

2014-01-01

Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min−1·gram of kidney weight−1 (gkw); n = 8; P resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min−1·gkw−1; n = 10; P resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min−1·gkw−1; n = 7; P resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min−1·gkw−1; n = 7; P Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products. PMID:24431202

Interaction between Mitochondrial Reactive Oxygen Species, Heme Oxygenase, and Nitric Oxide Synthase Stimulates Phagocytosis in Macrophages

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Andrea Müllebner

2018-01-01

Full Text Available BackgroundMacrophages are cells of the innate immune system that populate every organ. They are required not only for defense against invading pathogens and tissue repair but also for maintenance of tissue homeostasis and iron homeostasis.AimThe aim of this study is to understand whether heme oxygenase (HO and nitric oxide synthase (NOS contribute to the regulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX activity and phagocytosis, two key components of macrophage function.MethodsThis study was carried out using resting J774A.1 macrophages treated with hemin or vehicle. Activity of NOS, HO, or NOX was inhibited using specific inhibitors. Reactive oxygen species (ROS formation was determined by Amplex® red assay, and phagocytosis was measured using fluorescein isothiocyanate-labeled bacteria. In addition, we analyzed the fate of the intracellular heme by using electron spin resonance.ResultsWe show that both enzymes NOS and HO are essential for phagocytic activity of macrophages. NOS does not directly affect phagocytosis, but stimulates NOX activity via nitric oxide-triggered ROS production of mitochondria. Treatment of macrophages with hemin results in intracellular accumulation of ferrous heme and an inhibition of phagocytosis. In contrast to NOS, HO products, including carbon monoxide, neither clearly affect NOX activity nor clearly affect phagocytosis, but phagocytosis is accelerated by HO-mediated degradation of heme.ConclusionBoth enzymes contribute to the bactericidal activity of macrophages independently, by controlling different pathways.

Activated Macrophages as a Novel Determinant of Tumor Cell Radioresponse: The Role of Nitric Oxide-Mediated Inhibition of Cellular Respiration and Oxygen Sparing

International Nuclear Information System (INIS)

Jiang Heng; De Ridder, Mark; Verovski, Valeri N.; Sonveaux, Pierre; Jordan, Benedicte F.; Law, Kalun; Monsaert, Christinne; Van den Berge, Dirk L.; Verellen, Dirk; Feron, Olivier; Gallez, Bernard; Storme, Guy A.

2010-01-01

Purpose: Nitric oxide (NO), synthesized by the inducible nitric oxide synthase (iNOS), is known to inhibit metabolic oxygen consumption because of interference with mitochondrial respiratory activity. This study examined whether activation of iNOS (a) directly in tumor cells or (b) in bystander macrophages may improve radioresponse through sparing of oxygen. Methods and Materials: EMT-6 tumor cells and RAW 264.7 macrophages were exposed to bacterial lipopolysaccharide plus interferon-γ, and examined for iNOS expression by reverse transcription polymerase chain reaction, Western blotting and enzymatic activity. Tumor cells alone, or combined with macrophages were subjected to metabolic hypoxia and analyzed for radiosensitivity by clonogenic assay, and for oxygen consumption by electron paramagnetic resonance and a Clark-type electrode. Results: Both tumor cells and macrophages displayed a coherent picture of iNOS induction at transcriptional/translational levels and NO/nitrite production, whereas macrophages showed also co-induction of the inducible heme oxygenase-1, which is associated with carbon monoxide (CO) and bilirubin production. Activation of iNOS in tumor cells resulted in a profound oxygen sparing and a 2.3-fold radiosensitization. Bystander NO-producing, but not CO-producing, macrophages were able to block oxygen consumption by 1.9-fold and to radiosensitize tumor cells by 2.2-fold. Both effects could be neutralized by aminoguanidine, a metabolic iNOS inhibitor. An improved radioresponse was clearly observed at macrophages to tumor cells ratios ranging between 1:16 to 1:1. Conclusions: Our study is the first, as far as we are aware, to provide evidence that iNOS may induce radiosensitization through oxygen sparing, and illuminates NO-producing macrophages as a novel determinant of tumor cell radioresponse within the hypoxic tumor microenvironment.

21 CFR 862.3080 - Breath nitric oxide test system.

Science.gov (United States)

2010-04-01

... Systems § 862.3080 Breath nitric oxide test system. (a) Identification. A breath nitric oxide test system... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath nitric oxide test system. 862.3080 Section... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to...

21 CFR 868.5165 - Nitric oxide administration apparatus.

Science.gov (United States)

2010-04-01

... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to be used in conjunction with a ventilator or other breathing gas administration system. (b) Classification...

Nitric-phosphoric acid oxidation of solid and liquid organic materials

International Nuclear Information System (INIS)

Pierce, R.A.; Smith, J.R.; Poprik, D.C.

1995-01-01

Nitric-phosphoric acid oxidation has been developed specifically to address issues that face the Savannah River Site, other defense-related facilities, private industry, and small-volume generators such as university and medical laboratories. Initially tested to destroy and decontaminate SRS solid, Pu-contaminated job-control waste, the technology has also exhibited potential for remediating hazardous and mixed-hazardous waste forms. The process is unique to Savannah River and offers a valuable alternative to other oxidation processes that require extreme temperatures and/or elevated pressures. To address the broad categories of waste, many different organic compounds which represent a cross-section of the waste that must be treated have been successfully oxidized. Materials that have been quantitatively oxidized at atmospheric pressure below 180 degrees C include neoprene, cellulose, EDTA, tributylphosphate, and nitromethane. More stable compounds such as benzoic acid, polyethylene, oils, and resins have been completely decomposed below 200 degrees C and 10 psig. The process uses dilute nitric acid in a concentrated phosphoric acid media as the main oxidant for the organic compounds. Phosphoric acid allow nitric acid to be retained in solution well above its normal boiling point. The reaction forms NOx vapors which can be reoxidized and recycled using air and water. The addition of 0.001M Pd(II) reduces CO generation to near 1% of the released carbon gases. The advantages of this process are that it is straightforward, uses relatively inexpensive reagents, operates at relatively low temperature and pressure, and produces final solutions which are compatible with stainless steel equipment. For organic wastes, all carbon, hydrogen, and nitrogen are converted to gaseous products. If interfaced with an acid recovery system which converts NOx back to nitric acid, the net oxidizer would be oxygen from air

(1)H, (13)C, (15)N backbone and side-chain resonance assignment of Nostoc sp. C139A variant of the heme-nitric oxide/oxygen binding (H-NOX) domain.

Science.gov (United States)

Alexandropoulos, Ioannis I; Argyriou, Aikaterini I; Marousis, Kostas D; Topouzis, Stavros; Papapetropoulos, Andreas; Spyroulias, Georgios A

2016-10-01

The H-NOX (Heme-nitric oxide/oxygen binding) domain is conserved across eukaryotes and bacteria. In human soluble guanylyl cyclase (sGC) the H-NOX domain functions as a sensor for the gaseous signaling agent nitric oxide (NO). sGC contains the heme-binding H-NOX domain at its N-terminus, which regulates the catalytic site contained within the C-terminal end of the enzyme catalyzing the conversion of GTP (guanosine 5'-triphosphate) to GMP (guanylyl monophosphate). Here, we present the backbone and side-chain assignments of the (1)H, (13)C and (15)N resonances of the 183-residue H-NOX domain from Nostoc sp. through solution NMR.

Study of Nitric Oxide production by murine peritoneal macrophages induced by Brucella Lipopolysaccharide

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Kavoosi G

2001-07-01

Full Text Available Brueclla is a gram negative bacteria that causes Brucellosis. Lipopolysaccharide (LPS ", the pathogenic agent of Brucella is composed of O-chain, core oligosaccharide and lipid A. in addition, the structural and biological properties of different LPS extracted from different strains are not identical. The first defense system against LPS is nonspecific immunity that causes macrophage activation. Activated macrophages produce oxygen and nitrogen radicals that enhance the protection against intracellular pathogens.In this experiment LPS was extracted by hot phenol- water procedure and the effect of various LPSs on nitric oxide prodution by peritoneal mouse macrophages was examined.Our results demonstrated that the effect of LPS on nitric oxide production is concentration-dependent we observed the maximum response in concentration of 10-20 microgram per milliliter. Also our results demonstrate that LPS extracted from vaccine Brucella abortus (S 19 had a highe effect on nitric oxide production than the LPS from other strains

Fe-Chlorophyllin Promotes the Growth of Wheat Roots Associated with Nitric Oxide Generation

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Hui Jiang

2010-12-01

Full Text Available : Effects of Fe-chlorophyllin on the growth of wheat root were investigated in this study. We found that Fe-chlorophyllin can promote root growth. The production of nitric oxide in wheat root was detected using DAF-2DA fluorescent emission. The intensity of fluorescent in the presence of 0.1 mg/L Fe-chlorophyllin was near to that observed with the positive control of sodium nitroprusside (SNP, the nitric oxide donor. IAA oxidase activity decreased with all treatments of Fe-chlorophyllin from 0.01 to 10 mg/L. At the relatively lower Fe-chlorophyllin concentration of 0.1 mg/L, the activity of IAA oxidase displayed a remarkable decrease, being 40.1% lower than the control. Meanwhile, Fe-chlorophyllin treatment could increase the activities of reactive oxygen scavenging enzymes, such as superoxide dismutase (SOD and peroxidase (POD, as determined using non-denaturing polyacrylamide gel electrophoresis. These results indicate that Fe-chlorophyllin contributes to the growth of wheat root associated with nitric oxide generation.

Optical measurements of atomic oxygen concentration, temperature and nitric oxide production rate in flames

Science.gov (United States)

Myhr, Franklin Henry

An optical method for measuring nitric oxide (NO) production rates in flames was developed and characterized in a series of steady, one-dimensional, atmospheric-pressure laminar flames of 0.700 Hsb2/0.199 Nsb2/0.101 COsb2 or 0.700 CHsb4/0.300 Nsb2 (by moles) with dry air, with equivalence ratios from 0.79 to 1.27. Oxygen atom concentration, (O), was measured by two-photon laser-induced fluorescence (LIF), temperature was measured by ultraviolet Rayleigh scattering, and nitrogen concentration was calculated from supplied reactant flows; together this information was used to calculate the NO production rate through the thermal (Zel'dovich) mechanism. Measurements by two other techniques were compared with results from the above method. In the first comparison, gas sampling was used to measure axial NO concentration profiles, the slopes of which were multiplied by velocity to obtain total NO production rates. In the second comparison, LIF measurements of hydroxyl radical (OH) were used with equilibrium water concentrations and a partial equilibrium assumption to find (O). Nitric oxide production rates from all three methods agreed reasonably well. Photolytic interference was observed during (O) LIF measurements in all of the flames; this is the major difficulty in applying the optical technique. Photolysis of molecular oxygen in lean flames has been well documented before, but the degree of interference observed in the rich flames suggests that some other molecule is also dissociating; the candidates are OH, CO, COsb2 and Hsb2O. An extrapolative technique for removing the effects of photolysis from (O) LIF measurements worked well in all flames where NO production was significant. Using the optical method to measure NO production rates in turbulent flames will involve a tradeoff among spatial resolution, systematic photolysis error, and random shot noise. With the conventional laser system used in this work, a single pulse with a resolution of 700 mum measured NO

Nitric oxide in the psychobiology of mental disorders

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Altan Eşsizoğlu

2009-03-01

Full Text Available Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system. Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory functions, and on various neuronal mechanisms. Many studies have been conducted to investigate the location of nitric oxide in the central nervous system, its effect on anxiety and depression, its relationship with other neurotransmitters, and also about its role on neurotoxicity. There are clinical studies concerning the level of nitrate, a product of nitric oxide metabolism, and also experimental studies concerning its rewarding effect of alcohol and substance use, in patients with depression and schizophrenia. However, limited studies have been conducted to investigate its relationship with stress, which is an important factor in the etiology of psychiatric disorders. These studies demonstrate that nitric oxide is closely related with stress physiology.Nitric oxide is a neuromodulator, which is frequently being mentioned about nowadays in psychiatry. Clinical and experimental studies play an important role in the psychobiology of psychiatric disorders.

Cellular signaling with nitric oxide and cyclic GMP

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F. Murad

1999-11-01

Full Text Available During the past two decades, nitric oxide signaling has been one of the most rapidly growing areas in biology. This simple free radical gas can regulate an ever growing list of biological processes. In most instances nitric oxide mediates its biological effects by activating guanylyl cyclase and increasing cyclic GMP synthesis. However, the identification of effects of nitric oxide that are independent of cyclic GMP is also growing at a rapid rate. The effects of nitric oxide can mediate important physiological regulatory events in cell regulation, cell-cell communication and signaling. Nitric oxide can function as an intracellular messenger, neurotransmitter and hormone. However, as with any messenger molecule, there can be too much or too little of the substance and pathological events ensue. Methods to regulate either nitric oxide formation, metabolism or function have been used therapeutically for more than a century as with nitroglycerin therapy. Current and future research should permit the development of an expanded therapeutic armamentarium for the physician to manage effectively a number of important disorders. These expectations have undoubtedly fueled the vast research interests in this simple molecule.

Chronic deficit in nitric oxide elicits oxidative stress and augments T-type calcium-channel contribution to vascular tone of rodent arteries and arterioles

DEFF Research Database (Denmark)

Howitt, Lauren; Kuo, Ivana Y; Ellis, Anthie

2013-01-01

arteries in vitro and skeletal muscle arterioles in vivo to study the contribution of L-type (1 µmol/L nifedipine) and T-type (1 µmol/L mibefradil, 3 µmol/L NNC 55-0396) calcium channels to vascular tone, following acute or chronic inhibition of nitric oxide. Acute inhibition with l-NAME (10 µmol...... was reversed by acute scavenging of superoxide with tempol (1 mmol/L), or inhibition of NADPH oxidase with apocynin (500 µmol/L) or DPI (5 µmol/L). CONCLUSION: We conclude that nitric oxide deficit produces a significant increase in the contribution of Cav3.1 and Cav3.2 T-type calcium channels to vascular tone......, by regulating the bioavailability of reactive oxygen species produced by NADPH oxidase. Our data provide evidence for a novel causal link between nitric oxide deficit, oxidative stress, and T-type calcium channel function....

Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells.

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Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Cabilla, Jimena P; Duvilanski, Beatriz H

2007-03-01

We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.

Nitric Oxide is Required for Homeostasis of Oxygen and Reactive Oxygen Species in Barley Roots under Aerobic Conditions

DEFF Research Database (Denmark)

Gupta, Kapuganti J; Hebelstrup, Kim; Kruger, Nicholas J

2014-01-01

Oxygen, the terminal electron acceptor for mitochondrial electron transport, is vital for plants because of its role in the production of ATP by oxidative phosphorylation. While photosynthetic oxygen production contributes to the oxygen supply in leaves, reducing the risk of oxygen limitation of ...... electron transport chain (Gupta et al., 2011). Thus, NO could influence oxygen consumption under normal aerobic conditions in roots, and it is this specific function that is assessed here.......Oxygen, the terminal electron acceptor for mitochondrial electron transport, is vital for plants because of its role in the production of ATP by oxidative phosphorylation. While photosynthetic oxygen production contributes to the oxygen supply in leaves, reducing the risk of oxygen limitation...

Lower thermospheric nitric oxide concentrations derived from WINDII observations of the green nightglow continuum at 553.1 nm

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C. H. A. von Savigny

1999-11-01

Full Text Available Vertical profiles of nitric oxide in the altitude range 90 to 105 km are derived from 553 nm nightglow continuum measurements made with the Wind Imaging Interferometer (WINDII on the Upper Atmosphere Research Satellite (UARS. The profiles are derived under the assumption that the continuum emission is due entirely to the NO+O air afterglow reaction. Vertical profiles of the atomic oxygen density, which are required to determine the nitric oxide concentrations, are derived from coordinated WINDII measurements of the atomic oxygen OI 557.7 nm nightglow emission. Data coverage for local solar times ranging from 20 h to 04 h, and latitudes ranging from 42°S to 42°N, is achieved by zonally averaging and binning data obtained on 18 nights during a two-month period extending from mid-November 1992 until mid-January 1993. The derived nitric oxide concentrations are significantly smaller than those obtained from rocket measurements of the airglow continuum but they do compare well with model expectations and nitric oxide densities measured using the resonance fluorescence technique on the Solar Mesosphere Explorer satellite. The near-global coverage of the WINDII observations and the similarities to the nitric oxide global morphology established from other satellite measurements strongly suggests that the NO+O reaction is the major source of the continuum near 553 nm and that there is no compelling reason to invoke additional sources of continuum emission in this immediate spectral region.Key words. Atmospheric composition and structure (airglow and aurora; thermosphere – composition and chemistry; instruments and techniques

Nitric Oxide Metabolites and Asymmetric Dimethylarginine Concentrations in Breast Milk

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Hakan Öztürk

2017-04-01

Full Text Available Objective: Nitric oxide plays a preventive role in the development of necrotizing enterocolitis. Oral nitrite and nitrate intake has gained importance with the discovery of the conversion of nitrite to nitric oxide in acidic medium out of the synthesis of nitric oxide from L-arginine. Objective of this study was to examine the breast milk concentrations of nitric oxide and asymmetric dimethylarginine which is a competitive inhibitor of nitric oxide and to compare these concentrations in terms of gestational age and maturity of breast milk. Study Design: Forty-one women were included in the study. Milk samples were collected from 3 groups of mothers as term, late preterm and preterm on the postpartum days 3, 7 and 28. Results: When breast milk concentrations of nitric oxide were compared according to the postnatal day of the milk independently from gestational age; nitric oxide concentration was higher in the colostrum than in the transition milk and mature milk (p=0,035; p=0,001; respectively. For the comparison of asymmetric dimethylarginine concentrations among these groups and days; no statistically significant difference was observed in terms of gestational age and maturity of the milk (p=0.865, p=0.115; respectively. Conclusion: The highest nitric oxide concentration was found in the colostrum, suggesting that colostrum is a valuable food for newborns. Plasma concentrations of asymmetric dimethylarginine were negatively correlated with nitric oxide and did not show a correlation with breast milk, suggesting that asymmetric dimethylargininedoesn’t make nitric oxide inhibition in breast milk.

Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

Science.gov (United States)

Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

2016-01-01

Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.

Nitric oxide in the stress axis

OpenAIRE

Lopez-Figueroa, M.O.; Day, H.E.W.; Akil, H.; Watson, S.J.

1998-01-01

In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbichypothalamic- ...

Plant survival in a changing environment: the role of nitric oxide in plant responses to abiotic stress

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Marcela eSimontacchi

2015-11-01

Full Text Available Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant´s ontogeny and environmental fluctuations.Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant´s priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signalling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation.

Plant Survival in a Changing Environment: The Role of Nitric Oxide in Plant Responses to Abiotic Stress

Science.gov (United States)

Simontacchi, Marcela; Galatro, Andrea; Ramos-Artuso, Facundo; Santa-María, Guillermo E.

2015-01-01

Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant’s ontogeny and environmental fluctuations. Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV) radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant’s priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signaling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation. PMID:26617619

Non-thermal atmospheric pressure HF plasma source: generation of nitric oxide and ozone for bio-medical applications

Science.gov (United States)

Kühn, S.; Bibinov, N.; Gesche, R.; Awakowicz, P.

2010-01-01

A new miniature high-frequency (HF) plasma source intended for bio-medical applications is studied using nitrogen/oxygen mixture at atmospheric pressure. This plasma source can be used as an element of a plasma source array for applications in dermatology and surgery. Nitric oxide and ozone which are produced in this plasma source are well-known agents for proliferation of the cells, inhalation therapy for newborn infants, disinfection of wounds and blood ozonation. Using optical emission spectroscopy, microphotography and numerical simulation, the gas temperature in the active plasma region and plasma parameters (electron density and electron distribution function) are determined for varied nitrogen/oxygen flows. The influence of the gas flows on the plasma conditions is studied. Ozone and nitric oxide concentrations in the effluent of the plasma source are measured using absorption spectroscopy and electro-chemical NO-detector at variable gas flows. Correlations between plasma parameters and concentrations of the particles in the effluent of the plasma source are discussed. By varying the gas flows, the HF plasma source can be optimized for nitric oxide or ozone production. Maximum concentrations of 2750 ppm and 400 ppm of NO and O3, correspondingly, are generated.

Selective catalytic reduction of nitric oxide with acetaldehyde over NaY zeolite catalyst in lean exhaust feed

International Nuclear Information System (INIS)

Schmieg, Steven J.; Cho, Byong K.; Oh, Se H.

2004-01-01

Steady-state selective catalytic reduction (SCR) of nitric oxide (NO) was investigated under simulated lean-burn conditions using acetaldehyde (CH 3 CHO) as the reductant. This work describes the influence of catalyst space velocity and the impact of nitric oxide, acetaldehyde, oxygen, sulfur dioxide, and water on NO x reduction activity over NaY zeolite catalyst. Results indicate that with sufficient catalyst volume 90% NO x conversion can be achieved at temperatures relevant to light-duty diesel exhaust (150-350C). Nitric oxide and acetaldehyde react to form N 2 , HCN, and CO 2 . Oxygen is necessary in the exhaust feed stream to oxidize NO to NO 2 over the catalyst prior to reduction, and water is required to prevent catalyst deactivation. Under conditions of excess acetaldehyde (C 1 :N>6:1) and low temperature ( x conversion is apparently very high; however, the NO x conversion steadily declines with time due to catalytic oxidation of some of the stored (adsorbed) NO to NO 2 , which can have a significant impact on steady-state NO x conversion. With 250ppm NO in the exhaust feed stream, maximum NO x conversion at 200C can be achieved with =400ppm of acetaldehyde, with higher acetaldehyde concentrations resulting in production of acetic acid and breakthrough of NO 2 causing lower NO x conversion levels. Less acetaldehyde is necessary at lower NO concentrations, while more acetaldehyde is required at higher temperatures. Sulfur in the exhaust feed stream as SO 2 can cause slow deactivation of the catalyst by poisoning the adsorption and subsequent reaction of nitric oxide and acetaldehyde, particularly at low temperature

Improved in vivo performance of amperometric oxygen (PO2) sensing catheters via electrochemical nitric oxide generation/release.

Science.gov (United States)

Ren, Hang; Coughlin, Megan A; Major, Terry C; Aiello, Salvatore; Rojas Pena, Alvaro; Bartlett, Robert H; Meyerhoff, Mark E

2015-08-18

A novel electrochemically controlled release method for nitric oxide (NO) (based on electrochemical reduction of nitrite ions) is combined with an amperometric oxygen sensor within a dual lumen catheter configuration for the continuous in vivo sensing of the partial pressure of oxygen (PO2) in blood. The on-demand electrochemical NO generation/release method is shown to be fully compatible with amperometric PO2 sensing. The performance of the sensors is evaluated in rabbit veins and pig arteries for 7 and 21 h, respectively. Overall, the NO releasing sensors measure both venous and arterial PO2 values more accurately with an average deviation of -2 ± 11% and good correlation (R(2) = 0.97) with in vitro blood measurements, whereas the corresponding control sensors without NO release show an average deviation of -31 ± 28% and poor correlation (R(2) = 0.43) at time points >4 h after implantation in veins and >6 h in arteries. The NO releasing sensors induce less thrombus formation on the catheter surface in both veins and arteries (p < 0.05). This electrochemical NO generation/release method could offer a new and attractive means to improve the biocompatibility and performance of implantable chemical sensors.

Efficacy and residue analysis of nitric oxide fumigation of strawberries for control of Drosophila suzukii

Science.gov (United States)

Nitric oxide (NO) has been demonstrated as an effective fumigant against various insect pests on postharvest products under ultralow oxygen (ULO) conditions. NO showed efficacy against all life stages of insect pests with varied fumigation time and temperature, and had feasible cost-effectiveness to...

Reactive oxygen species and nitric oxide in plant mitochondria: origin and redundant regulatory systems.

Science.gov (United States)

Blokhina, Olga; Fagerstedt, Kurt V

2010-04-01

Plant mitochondria differ from their mammalian counterparts in many respects, which are due to the unique and variable surroundings of plant mitochondria. In green leaves, plant mitochondria are surrounded by ample respiratory substrates and abundant molecular oxygen, both resulting from active photosynthesis, while in roots and bulky rhizomes and fruit carbohydrates may be plenty, whereas oxygen levels are falling. Several enzymatic complexes in mitochondrial electron transport chain (ETC) are capable of reactive oxygen species (ROS) formation under physiological and pathological conditions. Inherently connected parameters such as the redox state of electron carriers in the ETC, ATP synthase activity and inner mitochondrial membrane potential, when affected by external stimuli, can give rise to ROS formation via complexes I and III, and by reverse electron transport (RET) from complex II. Superoxide radicals produced are quickly scavenged by superoxide dismutase (MnSOD), and the resulting H(2)O(2) is detoxified by peroxiredoxin-thioredoxin system or by the enzymes of ascorbate-glutathione cycle, found in the mitochondrial matrix. Arginine-dependent nitric oxide (NO)-releasing activity of enzymatic origin has been detected in plant mitochondria. The molecular identity of the enzyme is not clear but the involvement of mitochondria-localized enzymes responsible for arginine catabolism, arginase and ornithine aminotransferase has been shown in the regulation of NO efflux. Besides direct control by antioxidants, mitochondrial ROS production is tightly controlled by multiple redundant systems affecting inner membrane potential: NAD(P)H-dependent dehydrogenases, alternative oxidase (AOX), uncoupling proteins, ATP-sensitive K(+) channel and a number of matrix and intermembrane enzymes capable of direct electron donation to ETC. NO removal, on the other hand, takes place either by reactions with molecular oxygen or superoxide resulting in peroxynitrite, nitrite or nitrate

Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection by Trypanosoma cruzi.

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Triquell, María Fernanda; Díaz-Luján, Cintia; Romanini, María Cristina; Ramirez, Juan Carlos; Paglini-Oliva, Patricia; Schijman, Alejandro Gabriel; Fretes, Ricardo Emilio

2018-03-25

The innate immune response of the placenta may participate in the congenital transmission of Chagas disease through releasing reactive oxygen and nitrogen intermediates. Placental explants were cultured with 1 × 10 6 and 1 × 10 5 trypomastigotes of Tulahuen and Lucky strains and controls without parasites, and with the addition of nitric oxide synthase inhibitor Nω-Nitro-l-arginine methyl ester (l-NAME) and N-acetyl cysteine (NAC) as the reactive oxygen species (ROS) scavenger. Detachment of the syncytiotrophoblast (STB) was examined by histological analysis, and the nitric oxide synthase, endothelial (eNOS), and nitrotyrosine expressions were analyzed by immunohistochemistry, as well as the human chorionic gonadotrophin (hCG) levels in the culture supernatant through ELISA assays. Parasite load with qPCR using Taqman primers was quantified. The higher number of T. cruzi (10 6 ) increased placental infection, eNOS expression, nitrosative stress, and STB detachment, with the placental barrier being injured by oxidative stress. The higher number of parasites caused deleterious consequences to the placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage caused by trypomastigotes in placental villi but not that of the infection. Moreover, trophoblast eNOS played a key role in placental infection with the highest inoculum of Lucky, demonstrating the importance of the enzyme and nitrosative-oxidative stress in Chagas congenital transmission. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hypoxia tolerance, nitric oxide, and nitrite: Lessons from extreme animals

DEFF Research Database (Denmark)

Fago, Angela; B. Jensen, Frank

2015-01-01

survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and – in air breathing animals - redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite...... nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance...... of NO and nitrite signaling in the adaptive response to hypoxia in vertebrate animals....

On hydrazine oxidation in nitric acid media

International Nuclear Information System (INIS)

Zil'berman, B.Ya.; Lelyuk, G.A.; Mashkin, A.N.; Yasnovitskaya, A.L.

1988-01-01

Yield of products of radiolytic ( 60 Co gamma radiation) and chemical hydrazine (HZ) oxidation in nitric acid media is studied. Under radiolyte HZ oxidation by nitric acid hydrazoic acid, ammonia and nitrogen appear to be the reaction products. HN 3 yield maximum under HZN oxidation makes up ∼ 0.35 mol per a mol of oxiduzed HZN. Under chemical oxidation HZN is oxidized by HNO 3 according to reaction catalysed by technetium HN 3 yield makes up ∼ 0.35 mol per a mol of oxidized HZN. Radiation-chemical oxidation of HN 3 proceeds up to its complete decomposition, decomposition rate is comparable with HZ oxidation rate. Under the chemical oxidation HN 3 is more stable, it is slowly decomposed after complete HZ decomposition

Mitochondrial dysfunction associated with nitric oxide pathways in glutamate neurotoxicity.

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Manucha, Walter

Multiple mechanisms underlying glutamate-induced neurotoxicity have recently been discussed. Likewise, a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with neurodegeneration, oxidative stress, and inflammation. This article highlights nitric oxide, an atypical neurotransmitter synthesized and released on demand by the post-synaptic neurons, and has many important implications for nerve cell survival and differentiation. Consequently, synaptogenesis, synapse elimination, and neurotransmitter release, are nitric oxide-modulated. Interesting, an emergent role of nitric oxide pathways has been discussed as regards neurotoxicity from glutamate-induced apoptosis. These findings suggest that nitric oxide pathways modulation could prevent oxidative damage to neurons through apoptosis inhibition. This review aims to highlight the emergent aspects of nitric oxide-mediated signaling in the brain, and how they can be related to neurotoxicity, as well as the development of neurodegenerative diseases development. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

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Reid, Ian A.

1994-01-01

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

Reproducibility of exhaled nitric oxide measurements in overweight and obese adults

NARCIS (Netherlands)

Thijs, Willemien; de Mutsert, Renée; le Cessie, Saskia; Hiemstra, Pieter S.; Rosendaal, Frits R.; Middeldorp, Saskia; Rabe, Klaus F.

2014-01-01

Exhaled nitric oxide is a noninvasive measure of airway inflammation that can be detected by a handheld device. Obesity may influence the reproducibility of exhaled nitric oxide measurements, by - for instance - decreased expiratory reserve volume. We analyzed triple exhaled nitric oxide

Near infrared radiation protects against oxygen-glucose deprivation-induced neurotoxicity by down-regulating neuronal nitric oxide synthase (nNOS) activity in vitro.

Science.gov (United States)

Yu, Zhanyang; Li, Zhaoyu; Liu, Ning; Jizhang, Yunneng; McCarthy, Thomas J; Tedford, Clark E; Lo, Eng H; Wang, Xiaoying

2015-06-01

Near infrared radiation (NIR) has been shown to be neuroprotective against neurological diseases including stroke and brain trauma, but the underlying mechanisms remain poorly understood. In the current study we aimed to investigate the hypothesis that NIR may protect neurons by attenuating oxygen-glucose deprivation (OGD)-induced nitric oxide (NO) production and modulating cell survival/death signaling. Primary mouse cortical neurons were subjected to 4 h OGD and NIR was applied at 2 h reoxygenation. OGD significantly increased NO level in primary neurons compared to normal control, which was significantly ameliorated by NIR at 5 and 30 min post-NIR. Neither OGD nor NIR significantly changed neuronal nitric oxide synthase (nNOS) mRNA or total protein levels compared to control groups. However, OGD significantly increased nNOS activity compared to normal control, and this effect was significantly diminished by NIR. Moreover, NIR significantly ameliorated the neuronal death induced by S-Nitroso-N-acetyl-DL-penicillamine (SNAP), a NO donor. Finally, NIR significantly rescued OGD-induced suppression of p-Akt and Bcl-2 expression, and attenuated OGD-induced upregulation of Bax, BAD and caspase-3 activation. These results suggest NIR may protect against OGD at least partially through reducing NO production by down-regulating nNOS activity, and modulating cell survival/death signaling.

An epigrammatic (abridged) recounting of the myriad tales of astonishing deeds and dire consequences pertaining to nitric oxide and reactive oxygen species in mitochondria with an ancillary missive concerning the origins of apoptosis

International Nuclear Information System (INIS)

Heck, Diane E.; Kagan, Valerian E.; Shvedova, Anna A.; Laskin, Jeffrey D.

2005-01-01

Mitochondria play a central role in the life and death of cells. These organelles serve as the major energy-producing powerhouse, whereby the generation of ATP is associated with the utilization of molecular oxygen. A significant fraction (2-3%) of molecular oxygen consumed by mitochondria may be reduced in a one-electron fashion to yield a series of reactive oxygen species (ROS) such as superoxide anion radical, hydrogen peroxide, and hydroxyl radical. ROS are capable of damaging components of the electron transport apparatus and can, in turn, disrupt mitochondrial functioning, limiting cellular ATP levels and ultimately resulting in cell death. ROS-induced disruption of electron transport can perpetuate production of deleterious ROS and propagate mitochondrial damage. Consequently, mitochondria are highly enriched with water-soluble and lipid-soluble antioxidants (glutathione, ascorbate, Vitamin E, and coenzyme Q) and antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, catalase, thioredoxins, and peroxiredoxin. Another important antioxidant acting as a very effective scavenger of reactive lipid (peroxyl, alkoxyl) radicals is nitric oxide (NO) generated by mitochondrial nitric oxide synthase. However, NO can also be very disruptive to mitochondria function, a process facilitated by its high reactivity with superoxide. This interaction results in the formation of peroxynitrite, an oxidant capable of causing oxidative/nitrosative stress, further aggravating mitochondrial dysfunction, causing ATP depletion and damage to cells. Thus, in the most general sense, the effects of NO in mitochondria may be either protective or deleterious depending on specific conditions of local redox environment (redox potential, ratio of oxidized to reduced glutathione, transition metals, and the presence of other oxygen- and nitrogen-centered radicals)

Pancreatic nitric oxide and oxygen free radicals in the early stages of streptozotocin-induced diabetes mellitus in the rat

Directory of Open Access Journals (Sweden)

González E.

2000-01-01

Full Text Available The objective of the present study was to explore the regulatory mechanisms of free radicals during streptozotocin (STZ-induced pancreatic damage, which may involve nitric oxide (NO production as a modulator of cellular oxidative stress. Removal of oxygen species by incubating pancreatic tissues in the presence of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD (1 U/ml produced a decrease in nitrite levels (42% and NO synthase (NOS activity (50% in diabetic but not in control samples. When NO production was blocked by N G-monomethyl-L-arginine (L-NMMA (600 µM, SOD activity increased (15.21 ± 1.23 vs 24.40 ± 2.01 U/mg dry weight. The increase was abolished when the NO donor, spermine nonoate, was added to the incubating medium (13.2 ± 1.32. Lipid peroxidation was lower in diabetic tissues when PEG-SOD was added (0.40 ± 0.02 vs 0.20 ± 0.03 nmol/mg protein, and when L-NMMA blocked NOS activity in the incubating medium (0.28 ± 0.05; spermine nonoate (100 µM abolished the decrease in lipoperoxide level (0.70 ± 0.02. We conclude that removal of oxygen species produces a decrease in pancreatic NO and NOS levels in STZ-treated rats. Moreover, inhibition of NOS activity produces an increase in SOD activity and a decrease in lipoperoxidation in diabetic pancreatic tissues. Oxidative stress and NO pathway are related and seem to modulate each other in acute STZ-induced diabetic pancreas in the rat.

Protective Effect of Nitric Oxide (NO against Oxidative Damage in Larix gmelinii Seedlings under Ultraviolet-B Irradiation

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Haiqing Hu

2016-10-01

Full Text Available Ultraviolet-B (UV-B stress appears to be more striking than other research works because of the thin ozone layer. The protective influence of an exogenous nitric oxide donor and sodium nitroprusside (SNP on the growth properties of Larix gmelinii seedlings was investigated under ultraviolet-B radiation conditions. The results indicated that 0.1 mM SNP could effectively alleviate the damage caused by ultraviolet-B radiation, and improved the seedling growth properties, the relative water content, and photosynthetic pigment content in leaves. Additionally, the photosynthetic capacity and antioxidant enzyme activity were increased during the exposure. On the contrary, the damage caused by active oxygen was decreased in SNP-treated seedling leaves. The damage caused by ultraviolet-B radiation was slightly reduced after treating with 0.01 mM SNP. Nevertheless, treatment with 0.5 mM SNP had a negative effect under ultraviolet-B radiation. Furthermore, supplementing NO (nitric oxide improved the photosynthetic capacity and antioxidant enzyme activity and alleviated the damage of caused by active oxygen. The best effective concentration of SNP was 0.1 mM. Therefore, a suitable amount of exogenous NO can protect the Larix gmelinii seedlings and increase their tolerance to ultraviolet-B radiation.

Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli.

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Zengli Yu

2008-05-01

Full Text Available Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS and nitric oxide (NO determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx/atrogin-1 and muscle RING finger-1 (MuRF1, in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.

Role of the decreased nitric oxide bioavailability in the vascular complications of diabetes mellitus.

Science.gov (United States)

Masha, Andi; Dinatale, Stefano; Allasia, Stefano; Martina, Valentino

2011-09-01

This mini-review takes into consideration the physiology, synthesis and mechanisms of action of the nitric oxide (NO) and, subsequently, the causes and effects of the NO bioavailability impairment. In diabetes mellitus the reduced NO bioavailability is caused by the increased free radicals production, secondary to hyperglycemia. The reactive oxygen species oxidize the cofactors of the nitric oxide synthase, diminishing their active forms and consequently leading to a decreased NO production. Furthermore the decreased concentration of reduced glutathione results in a diminished production of nitrosoglutathione. These molecules are important intermediates of the NO pathway and physiologically activate the soluble guanylate cyclase. Their decrease in oxidative states of the cell, therefore, leads to a reduced cGMP production which represents the principal molecule that carries out NO's major effects. Finally we considered the eventual therapeutic strategies to improve NO bioavailability by acting on the causes of its decrease. Therefore the treatments proposed are based on the possibility to counteract the oxidation and, in this context, the physiopathological mechanisms strongly support the treatment with thiols.

Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: implications for the prevention of methamphetamine-induced neurotoxic damage.

Science.gov (United States)

Imam, S Z; Islam, F; Itzhak, Y; Slikker, W; Ali, S F

2000-09-01

Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. We have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts.

Nitric oxide-induced interstrand cross-links in DNA.

Science.gov (United States)

Caulfield, Jennifer L; Wishnok, John S; Tannenbaum, Steven R

2003-05-01

The DNA damaging effects of nitrous acid have been extensively studied, and the formation of interstrand cross-links have been observed. The potential for this cross-linking to occur through a common nitrosating intermediate derived from nitric oxide is investigated here. Using a HPLC laser-induced fluorescence (LIF) system, the amount of interstrand cross-link formed on nitric oxide treatment of the 5'-fluorescein-labeled oligomer ATATCGATCGATAT was determined. This self-complimentary sequence contains two 5'-CG sequences, which is the preferred site for nitrous acid-induced cross-linking. Nitric oxide was delivered to an 0.5 mM oligomer solution at 15 nmol/mL/min to give a final nitrite concentration of 652 microM. The resulting concentration of the deamination product, xanthine, in this sample was found to be 211 +/- 39 nM, using GC/MS, and the amount of interstrand cross-link was determined to be 13 +/- 2.5 nM. Therefore, upon nitric oxide treatment, the cross-link is found at approximately 6% of the amount of the deamination product. Using this system, detection of the cross-link is also possible for significantly lower doses of nitric oxide, as demonstrated by treatment of the same oligomer with NO at a rate of 18 nmol/mL/min resulting in a final nitrite concentration of 126 microM. The concentration of interstrand cross-link was determined to be 3.6 +/- 0.1 nM in this sample. Therefore, using the same dose rate, when the total nitric oxide concentration delivered drops by a factor of approximately 5, the concentration of cross-link drops by a factor of about 4-indicating a qausi-linear response. It may now be possible to predict the number of cross-links in a small genome based on the number of CpG sequences and the yield of xanthine derived from nitrosative deamination.

Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B.

Science.gov (United States)

Rao, Minxi; Smith, Brian C; Marletta, Michael A

2015-05-05

Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis. Bacterial nitric oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins regulates biofilm formation, playing an important role in protecting bacteria from oxidative stress and other environmental stresses. Biofilms are also an important part of symbiosis, allowing the organism to remain in a

Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

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Zeliha Selamoglu-Talas

2015-10-01

Full Text Available Background: The blocking of nitric oxide synthase (NOS activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nω-nitro-L-arginine methyl ester (L-NAME.Methods: Rats have been received L-NAME (40 mg/kg, intraperitoneally, NOS inhibitor for 15 days to produce hypertension and propolis (200mg/kg, by gavage the lastest 5 of 15 days.Results: There  were  the  increase  (P<0.001  in  the  malondialdehyde  levels  in  the  L-NAME treatment groups when compared to control rats, but the decrease (P<0.001 in the catalase activities in both brain and lung tissues. There were statistically changes (P<0.001 in these parameters of L-NAME+propolis treated rats as compared with L-NAME-treated group.Conclusion: The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress.

THE ESTROGENS / CHROMIUM INTERACTION IN THE NITRIC OXIDE GENERATION.

Science.gov (United States)

Sawicka, Ewa; Piwowar, Agnieszka; Musiala, Tomasz; Dlugosz, Anna

2017-05-01

The interaction of estrogens with environmental toxins in free radicals generation: reactive oxygen species (ROS) or reactive nitrogen species (RNS) which participates in cancerogenesis is not yet recognized. Chromium(VI) is widely present in environment. One of its toxicity pathway is free radicals generation. Estrogens have the ability to scavenge free radicals, but may also act as prooxidants. Both chromium(VI) and estrogens are classified by International Agency for Research on Cancer (IARC) as carcinogens, so synergistic effect seems very dangerous. The interaction of chromium and estrogens in ROS generation are partly described but there are no reports on estrogen/chromium interaction on nitric oxide (NO) generation. The aim of the study was to examine the interaction of chromium(VI) and 17-p-estradiol (E2) on NO level in human blood as well as the role of E2 metabolites: 4-hydroxyestradiol (4-OHE2) and 16a-hydroxyestrone (16α-OHE1) in these processes. The NO level was estimated with the diagnostic kit (Nitric Oxide Colorimetric Detection Kit from Arbor Assays) in human blood in vitm. The results showed that Cr(VI) in used concentration (0.5; 1.0 and 5.0 gg/mL) decreases significantly NO level in blood, acting antagonistically to E2 and 4-OHE2. Estrogens (E2, 4-OHE2 and 16α-OHEI) do not protect against inhibiting effect of Cr(VI) on nitric oxide generation in blood because after combined exposure the decreased production of NO in blood was noted. In conclusion, presented results provide the information about the character of estrogen/Cr(VI) interaction in NO level in human blood. It is important knowledge for cardio protected effect e.g., hormone replacement therapy in environmental or occupational exposure to Cr(VI), chromium supplementation, also important for cancer risk evaluation.

Catalytic abatement of nitrous oxide from nitric and production

NARCIS (Netherlands)

Oonk, J.

1998-01-01

Nitric acid production is identified as a main source of nitrous oxide. Options for emission reduction however are not available. TNO and Hydro Agri studied the technological and economic feasibility of catalytic decomposition of nitrous oxide in nitric acid tail-gases. Although in literature

Modeling the solar cycle change in nitric oxide in the thermosphere and upper mesosphere

International Nuclear Information System (INIS)

Fuller-Rowell, T.J.

1993-01-01

Measurements from the Solar Mesosphere Explorer (SME) satellite have shown that low-latitude nitric oxide densities at 110 km decrease by about a factor of 8 from January 1982 to April 1985. This time period corresponds to the descending phase of the last solar cycle where the monthly smoothed sunspot number decreased from more than 150 to less than 25. In addition, nitric oxide was observed to vary by a factor of 2 over a solar rotation, during high solar activity. A one-dimensional, globally averaged model of the thermosphere and upper mesosphere has been used to study the height distribution of nitric oxide (NO) and its response to changes in the solar extreme ultraviolet radiation (EUV) through the solar cycle and over a solar rotation. The primary source of nitric oxide is the reaction of excited atomic nitrogen, N( 2 D), with molecular oxygen. The atomic nitrogen is created by a number of ion-neutral reactions and by direct dissociation of molecular nitrogen by photons and photoelectrons. The occurrence of the peak nitric oxide density at or below 115 km is a direct consequence of ionization and dissociation of molecular nitrogen by photoelectrons, which are produced by the solar flux below 30.0 nm (XUV). Nitric oxide is shown to vary over the solar cycle by a factor of 7 at low latitudes in the lower thermosphere E region, due to the estimated change in the solar EUV flux, in good agreement with the SME satellite observations. The NO density is shown to be strongly dependent on the temperature profile in the lower thermosphere and accounts for the difference between the current model and previous work. Wavelengths less than 1.8 nm have little impact on the NO profile. A factor of 3 change in solar flux below 5.0 nm at high solar activity produced a factor of 2 change in the peak NO density, consistent with SME observations over a solar rotation; this change also lowered the peak to 100 km, consistent with rocket data. 52 refs., 10 figs., 5 tabs

Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor by endogenous nitric oxide.

Science.gov (United States)

Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu

2013-01-01

Ryanodine receptors (RyRs), located in the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane, are required for intracellular Ca2+ release that is involved in a wide range of cellular functions. In addition to Ca2+-induced Ca2+ release in cardiac cells and voltage-induced Ca2+ release in skeletal muscle cells, we recently identified another mode of intracellular Ca2+ mobilization mediated by RyR, i.e., nitric oxide-induced Ca2+ release (NICR), in cerebellar Purkinje cells. NICR is evoked by neuronal activity, is dependent on S-nitrosylation of type 1 RyR (RyR1) and is involved in the induction of long-term potentiation (LTP) of cerebellar synapses. In this addendum, we examined whether peroxynitrite, which is produced by the reaction of nitric oxide with superoxide, may also have an effect on the Ca2+ release via RyR1 and the cerebellar LTP. We found that scavengers of peroxynitrite have no significant effect either on the Ca2+ release via RyR1 or on the cerebellar LTP. We also found that an application of a high concentration of peroxynitrite does not reproduce neuronal activity-dependent Ca2+ release in Purkinje cells. These results support that NICR is induced by endogenous nitric oxide produced by neuronal activity through S-nitrosylation of RyR1.

Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

Science.gov (United States)

Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

2014-01-01

Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is

Estimation of the nitric oxide formed from hydroxylamine by Nitrosomonas

Science.gov (United States)

Anderson, J. H.

1965-01-01

1. Nitric oxide that was produced by reducing nitrite with an excess of acidified potassium iodide under nitrogen in Warburg respirometer flasks was rapidly absorbed by a solution of permanganate in sodium hydroxide held in the side arm. A small amount of nitrous oxide (or nitrogen) that was also produced was not absorbed. 2. By using a quantitative method for the recovery of nitrite from samples of the alkaline permanganate, it was found that the sum of the nitrite N formed and the residual nitrous oxide N was equivalent to the nitrite N used to generate the gases. These results showed that alkaline permanganate completely oxidized nitric oxide to nitrite. The method was suitable for determining 0·4–20 μmoles of nitric oxide. 3. The technique was used to determine the nitric oxide content of the nitrogenous gas that was produced anaerobically from hydroxylamine by an extract of the autotrophic nitrifying micro-organism Nitrosomonas in the presence of methylene blue as electron acceptor. PMID:14342235

The correlation between total antioxidant capacity and nitric oxide ...

African Journals Online (AJOL)

DNA damage was measured by comet assay and nitric oxide concentration was evaluated by Griess assay. TAC was measured in seminal plasma based on the generation of peroxyl radicals from 2,2-azinobis (2-amidino propane) dihydrochlorid (AAPH). Our results show that the means of DNA damage and nitric oxide ...

Surface modification of PLGA nanoparticles to deliver nitric oxide to inhibit Escherichia coli growth

Energy Technology Data Exchange (ETDEWEB)

Reger, Nina A. [Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282 (United States); Meng, Wilson S. [Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282 (United States); Gawalt, Ellen S., E-mail: gawalte@duq.edu [Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219 (United States)

2017-04-15

Highlights: • Thin film functionalized PLGA nanoparticles were modified to release nitric oxide from an s-nitrosothiol donor. • The nitric oxide modified nanoparticles were bacteriostatic against Escherichia coli. • The nitric oxide modified nanoparticles increased the effectiveness of tetracycline against Escherichia coli. • The modified nitric oxide nanoparticles did not exhibit cytotoxic effects against fibroblasts. - Abstract: Polymer nanoparticles consisting of poly (DL-lactic-co-glycolic acid) were surface functionalized to deliver nitric oxide. These biodegradable and biocompatible nanoparticles were modified with an S-nitrosothiol molecule, S-nitrosocysteamine, as the nitric oxide delivery molecule. S-nitrosocysteamine was covalently immobilized on the nanoparticle surface using small organic molecule linkers and carbodiimide coupling. Nanoparticle size, zeta potential, and morphology were determined using dynamic light scattering and scanning electron microscopy, respectively. Subsequent attachment of the S-nitrosothiol resulted in a nitric oxide release of 37.1 ± 1.1 nmol per milligram of nanoparticles under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli culture growth by 31.8%, indicating that the nitric oxide donor was effective at releasing nitric oxide even after attachment to the nanoparticle surface. Combining the nitric oxide modified nanoparticles with tetracycline, a commonly prescribed antibiotic for E. coli infections, increased the effectiveness of the antibiotic by 87.8%, which allows for lower doses of antibiotics to be used in order to achieve the same effect. The functionalized nanoparticles were not cytotoxic to mouse fibroblasts.

Surface modification of PLGA nanoparticles to deliver nitric oxide to inhibit Escherichia coli growth

International Nuclear Information System (INIS)

Reger, Nina A.; Meng, Wilson S.; Gawalt, Ellen S.

2017-01-01

Highlights: • Thin film functionalized PLGA nanoparticles were modified to release nitric oxide from an s-nitrosothiol donor. • The nitric oxide modified nanoparticles were bacteriostatic against Escherichia coli. • The nitric oxide modified nanoparticles increased the effectiveness of tetracycline against Escherichia coli. • The modified nitric oxide nanoparticles did not exhibit cytotoxic effects against fibroblasts. - Abstract: Polymer nanoparticles consisting of poly (DL-lactic-co-glycolic acid) were surface functionalized to deliver nitric oxide. These biodegradable and biocompatible nanoparticles were modified with an S-nitrosothiol molecule, S-nitrosocysteamine, as the nitric oxide delivery molecule. S-nitrosocysteamine was covalently immobilized on the nanoparticle surface using small organic molecule linkers and carbodiimide coupling. Nanoparticle size, zeta potential, and morphology were determined using dynamic light scattering and scanning electron microscopy, respectively. Subsequent attachment of the S-nitrosothiol resulted in a nitric oxide release of 37.1 ± 1.1 nmol per milligram of nanoparticles under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli culture growth by 31.8%, indicating that the nitric oxide donor was effective at releasing nitric oxide even after attachment to the nanoparticle surface. Combining the nitric oxide modified nanoparticles with tetracycline, a commonly prescribed antibiotic for E. coli infections, increased the effectiveness of the antibiotic by 87.8%, which allows for lower doses of antibiotics to be used in order to achieve the same effect. The functionalized nanoparticles were not cytotoxic to mouse fibroblasts.

Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway.

Science.gov (United States)

Achike, Francis I; Kwan, Chiu-Yin

2003-09-01

1. Nitric oxide (NO) is formed enzymatically from l-arginine in the presence of nitric oxide synthase (NOS). Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines. 2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO. 3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection. 4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or

Cannula sensor for nitric oxide detection

Energy Technology Data Exchange (ETDEWEB)

Glazier, S.A. [National Institute of Standard and Technology, Gaithersburg, MD (United States)

1995-12-31

Nitric oxide (NO) has received much attention because of its numerous roles in mammalian systems. It has been found in the brain and nervous system to act as a neurotransmitter, in blood vessels as a blood pressure regulator, in the immune system to act as a bactericide and tumorcide, and in other postulated roles as well. Nitric oxide is produced in mammalian cells by the enzyme nitric oxide synthetase. Once produced, NO is oxidized or reacts rapidly with components in living systems and hence has a short half-life. Only a few sensors have been constructed which can detect NO at nanomolar to micromolar levels found in these systems. We are currently examining the use of a cannula sensor employing oxyhemoglobin for NO detection. This sensor continuously draws in liquid sample at a low rate and immediately reacts it with oxyhemoglobin. The absorbance changes which accompany the reaction are monitored. The sensor has a linear response range from approximately 50 to 1000 nM of NO in aqueous solution. Its utility in monitoring NO produced by stimulated murine macrophage cells (RAW 264.7) in culture is currently being examined. The sensor design is generic in that it can also employ fluorescence and chemiluminescence detection chemistries which may allow lower detection limits to be achieved. Details of the sensor`s performance will be given.

Mechanisms of electrochemical reduction and oxidation of nitric oxide

NARCIS (Netherlands)

Vooys, de A.C.A.; Beltramo, G.L.; Riet, van B.; Veen, van J.A.R.; Koper, M.T.M.

2004-01-01

A summary is given of recent work on the reactivity of nitric oxide on various metal electrodes. The significant differences between the reactivity of adsorbed NO and NO in solution are pointed out, both for the reduction and the oxidation reaction(s). Whereas adsorbed NO can be reduced only to

Oxidation of urate by a therapeutic nitric oxide/air mixture

International Nuclear Information System (INIS)

Hicks, M.; Nguyen, L.; Day, R.; Rogers, P.

1996-01-01

Full text: Little is known about the potential toxicological consequences of therapeutic exposure of lung tissue to inhaled nitric oxide (NO). This route of administration is currently being successfully employed for the treatment of pulmonary hypertension and other lung pathologies including acute reperfusion injury in lung transplant patients. The toxicity of NO lies in its ability to act as an oxidant either in its own right or in concert with oxygen or with the superoxide free radical. One important interaction may be the reaction of these products with protective antioxidants in the lung epithelial lining fluid. One such antioxidant found in significant concentrations in both upper and lower airways is uric acid. In the present study, urate solutions (30μM) were exposed to a therapeutic concentration of NO gas, (35 ppm in air), for up to 90 minutes. Oxidative changes were followed spectrophotometrically and by HPLC. Significant loss of uric acid was observed with a concomitant formation of nitrite and allantoin, the stable oxidation product of NO and the major oxidation product of uric acid, respectively. No oxidation of urate was observed in the presence of air alone or when urate was incubated with nitrite. Uric acid oxidation could also be prevented by passing the NO / air stream through 10% KOH before the uric acid solution. This strategy removed trace amounts of higher oxides of nitrogen, (especially NO 2 ), from the NO / air stream. Thus, therapeutic inhalation of NO may deplete soluble antioxidants such as uric acid, especially during long-term chronic exposure unless care is taken to minimise formation of higher oxides of nitrogen

Relative rates of nitric oxide and nitrous oxide production by nitrifiers, denitrifiers, and nitrate respirers

Science.gov (United States)

Anderson, I. C.; Levine, J. S.

1986-01-01

An account is given of the atmospheric chemical and photochemical effects of biogenic nitric and nitrous oxide emissions. The magnitude of the biogenic emission of NO is noted to remain uncertain. Possible soil sources of NO and N2O encompass nitrification by autotropic and heterotropic nitrifiers, denitrification by nitrifiers and denitrifiers, nitrate respiration by fermenters, and chemodenitrification. Oxygen availability is the primary determinant of these organisms' relative rates of activity. The characteristics of this major influence are presently investigated in light of the effect of oxygen partial pressure on NO and N2O production by a wide variety of common soil-nitrifying, denitrifying, and nitrate-respiring bacteria under laboratory conditions. The results obtained indicate that aerobic soils are primary sources only when there is sufficient moisture to furnish anaerobic microsites for denitrification.

Zeolites as catalyzer to environmental control. Nitric oxide removal

International Nuclear Information System (INIS)

Montes, C.; Zapata N, M; Villa H, A.L.

1995-01-01

Zeolites and the microporous materials related to them are a class of environmental catalysts, it which are used to remove the produced gases in combustion process (as mobile sources). In this work the importance that has catalysis for environment improvement is emphasized. A review of recent progress in the use of certain zeolitic material as catalysts for nitric oxide elimination of combustion systems is presented. More used nitric oxide removal methods are presented, as well as its advantages and disadvantages. Furthermore, it is emphasized on the need of accomplishing more investigation projects on the development of an active catalyst for the decomposition of the nitric oxide in its elements (N and O)

Pu-erh Tea Reduces Nitric Oxide Levels in Rats by Inhibiting Inducible Nitric Oxide Synthase Expression through Toll-Like Receptor 4

Science.gov (United States)

Xu, Yang; Wang, Guan; Li, Chunjie; Zhang, Min; Zhao, Hang; Sheng, Jun; Shi, Wei

2012-01-01

Pu-erh tea undergoes a unique fermentation process and contains theabrownins, polysaccharides and caffeine; although it is unclear about which component is associated with the down regulation of nitric oxide levels or how this process is mediated. To address this question we examined the effects of pu-erh tea on nitric oxide synthase (NOS) genes. Cohorts of rats were separately given four-week treatments of water as control, pu-erh tea, or the tea components: theabrownins, caffeine or polysaccharides. Five experimental groups were injected with lipopolysaccharides (LPS) to induce nitric oxide (NO) production, while the corresponding five control groups were injected with saline as a negative control. The serum and liver NO concentrations were examined and the NOS expression of both mRNA and protein was measured in liver. The results showed that the rats which were fed pu-erh tea or polysaccharides had lower levels of NO which corresponded with the down-regulation of inducible nitric oxide synthase (iNOS) expression. We further demonstrate that this effect is mediated through reduction of Toll-like receptor 4 (TLR4) signaling. Thus we find that the polysaccharide components in pu-erh tea reduce NO levels in an animal model by inhibiting the iNOS expression via signaling through TLR4. PMID:22837686

Antimicrobial Activity of Nitric Oxide-Releasing Ti-6Al-4V Metal Oxide

Science.gov (United States)

Reger, Nina A.; Meng, Wilson S.; Gawalt, Ellen S.

2017-01-01

Titanium and titanium alloy materials are commonly used in joint replacements, due to the high strength of the materials. Pathogenic microorganisms can easily adhere to the surface of the metal implant, leading to an increased potential for implant failure. The surface of a titanium-aluminum-vanadium (Ti-6Al-4V) metal oxide implant material was functionalized to deliver an small antibacterial molecule, nitric oxide. S-nitroso-penicillamine, a S-nitrosothiol nitric oxide donor, was covalently immobilized on the metal oxide surface using self-assembled monolayers. Infrared spectroscopy was used to confirm the attachment of the S-nitrosothiol donor to the Ti-Al-4V surface. Attachment of S-nitroso-penicillamine resulted in a nitric oxide (NO) release of 89.6 ± 4.8 nmol/cm2 under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli and Staphylococcus epidermidis growth by 41.5 ± 1.2% and 25.3 ± 0.6%, respectively. Combining the S-nitrosothiol releasing Ti-6Al-4V with tetracycline, a commonly-prescribed antibiotic, increased the effectiveness of the antibiotic by 35.4 ± 1.3%, which allows for lower doses of antibiotics to be used. A synergistic effect of ampicillin with S-nitroso-penicillamine-modified Ti-6Al-4V against S. epidermidis was not observed. The functionalized Ti-6Al-4V surface was not cytotoxic to mouse fibroblasts. PMID:28635681

SOIL NITROUS OXIDE, NITRIC OXIDE, AND AMMONIA EMISSIONS FROM A RECOVERING RIPARIAN ECOSYSTEM IN SOUTHERN APPALACHIA

Science.gov (United States)

The paper presents two years of seasonal nitric oxide, ammonia, and nitrous oxide trace gas fluxes measured in a recovering riparian zone with cattle excluded and in an adjacent riparian zone grazed by cattle. In the recovering riparian zone, average nitric oxide, ammonia, and ni...

Arsenic triggers the nitric oxide (NO) and S-nitrosoglutathione (GSNO) metabolism in Arabidopsis

International Nuclear Information System (INIS)

Leterrier, Marina; Airaki, Morad; Palma, José M.; Chaki, Mounira; Barroso, Juan B.; Corpas, Francisco J.

2012-01-01

Environmental contamination by arsenic constitutes a problem in many countries, and its accumulation in food crops may pose health complications for humans. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved at various levels in the mechanism of responding to environmental stress in higher plants. Using Arabidopsis seedlings exposed to different arsenate concentrations, physiological and biochemical parameters were analyzed to determine the status of ROS and RNS metabolisms. Arsenate provoked a significant reduction in growth parameters and an increase in lipid oxidation. These changes were accompanied by an alteration in antioxidative enzymes and the nitric oxide (NO) metabolism, with a significant increase in NO content, S-nitrosoglutathione reductase (GSNOR) activity and protein tyrosine nitration as well as a concomitant reduction in glutathione and S-nitrosoglutathione (GSNO) content. Our results indicate that 500 μM arsenate (AsV) causes nitro-oxidative stress in Arabidopsis, being the glutathione reductase and the GSNOR activities clearly affected. - Highlights: ► In Arabidopsis, arsenate provokes damages in the membrane integrity of root cells. ► As induces an oxidative stress according to an increase in lipid oxidation. ► NO content and protein tyrosine nitration increases under arsenate stress. ► Arsenate provokes a reduction of GSH, GSSG and GSNO content. ► Arsenate induces a nitro-oxidative stress in Arabidopsis. - Arsenic stress affects nitric oxide (NO) and glutathione (GSH) metabolism which provokes a nitro-oxidative stress.

In Vivo Imaging of Nitric Oxide by Magnetic Resonance Imaging Techniques

Directory of Open Access Journals (Sweden)

Rakesh Sharma

2014-01-01

Full Text Available Nitric oxide (NO biosensors are novel tools for real-time bioimaging of tissue oxygen changes and physiological monitoring of tissue vasculature. Nitric oxide behavior further enhances its role in mapping signal transduction at the molecular level. Spectrometric electron paramagnetic resonance (EPR and fluorometric imaging are well known techniques with the potential for in vivo bioimaging of NO. In tissues, NO is a specific target of nitrosyl compounds for chemical reaction, which provides a unique opportunity for application of newly identified NO biosensors. However, the accuracy and sensitivity of NO biosensors still need to be improved. Another potential magnetic resonance technique based on short term NO effects on proton relaxation enhancement is magnetic resonance imaging (MRI, and some NO biosensors may be used as potent imaging contrast agents for measurement of tumor size by MRI combined with fluorescent imaging. The present review provides supporting information regarding the possible use of nitrosyl compounds as NO biosensors in MRI and fluorescent bioimaging showing their measurement limitations and quantitative accuracy. These new approaches open a perspective regarding bioimaging of NO and the in vivo elucidation of NO effects by magnetic resonance techniques.

Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China); Zhang, Qunye, E-mail: wz.zhangqy@sdu.edu.cn [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong (China); Li, Guorong, E-mail: grli@sdnu.edu.cn [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China)

2015-03-13

As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.

Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

International Nuclear Information System (INIS)

Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi; Zhang, Qunye; Li, Guorong

2015-01-01

As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation

Osteopontin protects against hyperoxia-induced lung injury by inhibiting nitric oxide synthases.

Science.gov (United States)

Zhang, Xiang-Feng; Liu, Shuang; Zhou, Yu-Jie; Zhu, Guang-Fa; Foda, Hussein D

2010-04-05

Exposure of adult mice to more than 95% O(2) produces a lethal injury by 72 hours. Nitric oxide synthase (NOS) is thought to contribute to the pathophysiology of murine hyperoxia-induced acute lung injury (ALI). Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of nitric oxide production. However, the relationship between nitric oxide and endogenous OPN in lung tissue during hyperoxia-induced ALI has not yet been elucidated, thus we examined the role that OPN plays in the hyperoxia-induced lung injury and its relationships with NOS. One hundred and forty-four osteopontin knock-out (KO) mice and their matched wild type background control (WT) were exposed in sealed cages > 95% oxygen or room air for 24- 72 hours, and the severity of lung injury was assessed; expression of OPN, endothelial nitric oxide synthase (eNOS) and iNOS mRNA in lung tissues at 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR); immunohistochemistry (IHC) was performed for the detection of iNOS, eNOS, and OPN protein in lung tissues. OPN KO mice developed more severe acute lung injury at 72 hours of hyperoxia. The wet/dry weight ratio increased to 6.85 +/- 0.66 in the KO mice at 72 hours of hyperoxia as compared to 5.31 +/- 0.92 in the WT group (P < 0.05). iNOS mRNA (48 hours: 1.04 +/- 0.08 vs. 0.63 +/- 0.09, P < 0.01; 72 hours: 0.89 +/- 0.08 vs. 0.72 +/- 0.09, P < 0.05) and eNOS mRNA (48 hours: 0.62 +/- 0.08 vs. 0.43 +/- 0.09, P < 0.05; 72 hours: 0.67 +/- 0.08 vs. 0.45 +/- 0.09, P < 0.05) expression was more significantly increased in OPN KO mice than their matched WT mice when exposed to hyperoxia. IHC study showed higher expression of iNOS (20.54 +/- 3.18 vs. 12.52 +/- 2.46, P < 0.05) and eNOS (19.83 +/- 5.64 vs. 9.45 +/- 3.82, P < 0.05) in lung tissues of OPN KO mice at 72 hours of hyperoxia. OPN can protect against

Storm time variation of radiative cooling of thermosphere by nitric oxide emission

Science.gov (United States)

Krishna, M. V. Sunil; Bag, Tikemani; Bharti, Gaurav

2016-07-01

The fundamental vibration-rotation band emission (Δν=1, Δ j=0,± 1) by nitric oxide (NO) at 5.3 µm is one of the most important cooling mechanisms in thermosphere. The collisional vibrational excitation of NO(ν=0) by impact with atomic oxygen is the main source of vibrationally excited nitric oxide. The variation of NO density depends on latitude, longitude and season. The present study aims to understand how the radiative flux gets influenced by the severe geomagnetic storm conditions. The variation of Nitric Oxide (NO) radiative flux exiting thermosphere is studied during the superstorm event of 7-12 November, 2004. The observations of TIMED/SABER suggest a strong anti-correlation with the O/N_2 ratio observed by GUVI during the same period. On a global scale the NO radiative flux showed an enhancement during the main phase on 8 November, 2004, whereas maximum depletion in O/N_2 is observed on 10 November, 2004. Both O/N_2 and NO radiative flux were found to propagate equatorward due to the effect of meridional wind resulting from joule and particle heating in polar region. Larger penetrations is observed in western longitude sectors. These observed variations are effectively connected to the variations in neutral densities. In the equatorial sectors, O/N_2 shows enhancement but almost no variation in radiative flux is observed. The possible reasons for the observed variations in NO radiative emission and O/N_2 ratios are discussed in the light of equator ward increase in the densities and prompt penetration.

Non-asthmatic patients show increased exhaled nitric oxide concentrations

Directory of Open Access Journals (Sweden)

Beatriz M. Saraiva-Romanholo

2009-01-01

Full Text Available OBJECTIVE: Evaluate whether exhaled nitric oxide may serve as a marker of intraoperative bronchospasm. INTRODUCTION: Intraoperative bronchospasm remains a challenging event during anesthesia. Previous studies in asthmatic patients suggest that exhaled nitric oxide may represent a noninvasive measure of airway inflammation. METHODS: A total of 146,358 anesthesia information forms, which were received during the period from 1999 to 2004, were reviewed. Bronchospasm was registered on 863 forms. From those, three groups were identified: 9 non-asthmatic patients (Bronchospasm group, 12 asthmatics (Asthma group and 10 subjects with no previous airway disease or symptoms (Control group. All subjects were submitted to exhaled nitric oxide measurements (parts/billion, spirometry and the induced sputum test. The data was compared by ANOVA followed by the Tukey test and Kruskal-Wallis followed by Dunn's test. RESULTS: The normal lung function test results for the Bronchospasm group were different from those of the asthma group (p <0.05. The median percentage of eosinophils in induced sputum was higher for the Asthma [2.46 (0.45-6.83] compared with either the Bronchospasm [0.55 (0-1.26] or the Control group [0.0 (0] (p <0.05; exhaled nitric oxide followed a similar pattern for the Asthma [81.55 (57.6-86.85], Bronchospasm [46.2 (42.0 -62.6] and Control group [18.7 (16.0-24.7] (p< 0.05. CONCLUSIONS: Non-asthmatic patients with intraoperative bronchospasm detected during anesthesia and endotracheal intubation showed increased expired nitric oxide.

On the Effects of Reactive Oxygen Species and Nitric Oxide on Red Blood Cell Deformability

Directory of Open Access Journals (Sweden)

Lukas Diederich

2018-05-01

Full Text Available The main function of red blood cells (RBCs is the transport of respiratory gases along the vascular tree. To fulfill their task, RBCs are able to elastically deform in response to mechanical forces and, pass through the narrow vessels of the microcirculation. Decreased RBC deformability was observed in pathological conditions linked to increased oxidative stress or decreased nitric oxide (NO bioavailability, like hypertension. Treatments with oxidants and with NO were shown to affect RBC deformability ex vivo, but the mechanisms underpinning these effects are unknown. In this study we investigate whether changes in intracellular redox status/oxidative stress or nitrosation reactions induced by reactive oxygen species (ROS or NO may affect RBC deformability. In a case-control study comparing RBCs from healthy and hypertensive participants, we found that RBC deformability was decreased, and levels of ROS were increased in RBCs from hypertensive patients as compared to RBCs from aged-matched healthy controls, while NO levels in RBCs were not significantly different. To study the effects of oxidants on RBC redox state and deformability, RBCs from healthy volunteers were treated with increasing concentrations of tert-butylhydroperoxide (t-BuOOH. We found that high concentrations of t-BuOOH (≥ 1 mM significantly decreased the GSH/GSSG ratio in RBCs, decreased RBC deformability and increased blood bulk viscosity. Moreover, RBCs from Nrf2 knockout (KO mice, a strain genetically deficient in a number of antioxidant/reducing enzymes, were more susceptible to t-BuOOH-induced impairment in RBC deformability as compared to wild type (WT mice. To study the role of NO in RBC deformability we treated RBC suspensions from human volunteers with NO donors and nitrosothiols and analyzed deformability of RBCs from mice lacking the endothelial NO synthase (eNOS. We found that NO donors induced S-nitrosation of the cytoskeletal protein spectrin, but did not affect

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

Science.gov (United States)

Ugusman, Azizah; Zakaria, Zaiton; Hui, Chua Kien; Nordin, Nor Anita Megat Mohd

2010-07-01

Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

Role of nitric oxide in glucose-, fructose and galactose-induced ...

African Journals Online (AJOL)

Previous studies have shown that the infusion of glucose, fructose and galactose resulted in significant increases in intestinal glucose uptake (IGU) and the role of nitric oxide in these responses was not known. The present study was designed to investigate the role of nitric oxide in the observed increases in IGU.

Hepatocytes Determine the Hypoxic Microenvironment and Radiosensitivity of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration

International Nuclear Information System (INIS)

Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra; De Ridder, Mark

2013-01-01

Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription–polymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assess hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The radiosensitizing effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxide–producing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes

Hepatocytes Determine the Hypoxic Microenvironment and Radiosensitivity of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration

Energy Technology Data Exchange (ETDEWEB)

Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

2013-03-01

Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription–polymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assess hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The radiosensitizing effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxide–producing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes.

Pain modulation by nitric oxide in the spinal cord.

Directory of Open Access Journals (Sweden)

Marco Aurelio M Freire

2009-09-01

Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

Nitric oxide-related drug targets in headache

DEFF Research Database (Denmark)

Olesen, Jes

2010-01-01

SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called del......SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so......-called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache....... Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Similar evidence suggests an important role of NO in the tension-type headache and cluster headache. These very strong data from human...

Influence of nitric oxide on histamine and carbachol – induced ...

African Journals Online (AJOL)

The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad – Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase ...

Reduction of nitric oxide level enhances the radiosensitivity of hypoxic non-small cell lung cancer

International Nuclear Information System (INIS)

Saleem, Wael; Suzuki, Yoshiyuki; Mobaraki, Abdulelah; Yoshida, Yukari; Noda, Shinei; Saitoh, Jun-ichi; Nakano, Takashi

2011-01-01

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (E-TKI) resistance has emerged as an important clinical issue. To overcome this resistance, researchers have examined different modalities, either for use as a monotherapy or in combination with E-TKI therapy. In the present study, we investigated whether a decrease in nitric oxide (NO) levels affects the radiosensitization of non-small cell lung cancer (NSCLC) cell lines. A549 and H3255 NSCLC cells were examined. They were subjected to hypoxic conditions and monotherapy, or combined therapy using radiation and N G -monomethyl- L -arginine, monoacetate (LNMMA). Reductions in nitric oxide levels enhanced the radiosensitivity of both cell lines and significantly reduced the expression of both hypoxia-inducible factor-1α (HIF-1α) and EGFR in H3255 cells compared to A549 cells. Since NO is significantly associated with cell metabolism, we measured the levels of pyruvate dehydrogenase kinase-1 (PDK-1), reactive oxygen species, and oxygen and observed that the expression of PDK-1 was significantly reduced. This reduction was seen simultaneously after the silencing of HIF-1α; however, not following LNMMA treatment. The oxygen concentration was significantly increased in the treated cells, and their viability decreased in parallel. Reactive oxygen species were decreased after LNMMA and radiation treatment. Adding EGFR-TKI to cells with reduced NO levels further suppressed cell viability when combined with radiation. This study suggests that a reduction in the NO level might substantially overcome the radioresistance of mutant NSCLC cells. (author)

Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

DEFF Research Database (Denmark)

Afzelius, Pia; Bazeghi, Nassim; Bie, Peter

2011-01-01

Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this ...

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells

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Azizah Ugusman

2010-01-01

Full Text Available OBJECTIVE: Nitric oxide produced by endothelial nitric oxide synthase (eNOS possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs. METHODS: HUVECs were divided into four groups: control, treatment with 180 μM hydrogen peroxide (H2O2, treatment with 150 μg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H2O2 for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. RESULTS: Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. CONCLUSION: Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

Efficacy of Nitric Oxide Fumigation for Controlling Codling Moth in Apples

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Yong-Biao Liu

2016-12-01

Full Text Available Nitric oxide (NO fumigation under ultralow oxygen (ULO conditions was studied for its efficacy in controlling codling moth and effects on postharvest quality of apples. NO fumigation was effective against eggs and larvae of different sizes on artificial diet in 48 h treatments. Small larvae were more susceptible to nitric oxide than other stages at 0.5% NO concentration. There were no significant differences among life stages at 1.0% to 2.0% NO concentrations. In 24 h treatments of eggs, 3.0% NO fumigation at 2 °C achieved 100% egg mortality. Two 24 h fumigation treatments of infested apples containing medium and large larvae with 3.0% and 5.0% NO resulted in 98% and 100% mortalities respectively. Sound apples were also fumigated with 5.0% NO for 24 h at 2 °C to determine effects on apple quality. The fumigation treatment was terminated by flushing with nitrogen and had no negative impact on postharvest quality of apples as measured by firmness and color at 2 and 4 weeks after fumigation. This study demonstrated that NO fumigation was effective against codling moth and safe to apple quality, and therefore has potential to become a practical alternative to methyl bromide fumigation for control of codling moth in apples.

Efficacy of Nitric Oxide Fumigation for Controlling Codling Moth in Apples.

Science.gov (United States)

Liu, Yong-Biao; Yang, Xiangbing; Simmons, Gregory

2016-12-02

Nitric oxide (NO) fumigation under ultralow oxygen (ULO) conditions was studied for its efficacy in controlling codling moth and effects on postharvest quality of apples. NO fumigation was effective against eggs and larvae of different sizes on artificial diet in 48 h treatments. Small larvae were more susceptible to nitric oxide than other stages at 0.5% NO concentration. There were no significant differences among life stages at 1.0% to 2.0% NO concentrations. In 24 h treatments of eggs, 3.0% NO fumigation at 2 °C achieved 100% egg mortality. Two 24 h fumigation treatments of infested apples containing medium and large larvae with 3.0% and 5.0% NO resulted in 98% and 100% mortalities respectively. Sound apples were also fumigated with 5.0% NO for 24 h at 2 °C to determine effects on apple quality. The fumigation treatment was terminated by flushing with nitrogen and had no negative impact on postharvest quality of apples as measured by firmness and color at 2 and 4 weeks after fumigation. This study demonstrated that NO fumigation was effective against codling moth and safe to apple quality, and therefore has potential to become a practical alternative to methyl bromide fumigation for control of codling moth in apples.

Evaluation of salivary oxidate stress biomarkers, nitric oxide and C-reactive protein in patients with oral lichen planus and burning mouth syndrome.

Science.gov (United States)

Tvarijonaviciute, Asta; Aznar-Cayuela, Cristina; Rubio, Camila P; Ceron, José J; López-Jornet, Pia

2017-05-01

The aim of this study was to evaluate oxidative stress factors and C-reactive protein in the saliva of patients with oral lichen planus (OLP) and burning mouth syndrome (BMS). This consecutive, cross-sectional study included 20 patients with OLP, 19 with burning mouth syndrome (BMS), and 31 control subjects. The oral cavity of each patient was examined and patients responded to a quality of life questionnaire (OHIP-14) and the xerostomia inventory. The following parameters were measured in whole non-stimulated saliva: trolox equivalent antioxidant capacity (TEAC); total antioxidant capacity (TAC); cupric reducing antioxidant capacity (CUPRAC); ferric reducing ability of plasma (FRAP); C-reactive protein (CRP); nitric oxide; nitrates; and nitrites. The OLP group presented statistically significant differences in reactive oxygen species (ROS) (29 600 cps) in comparison with the control group (39 679 cps) (P < 0.05). In the BMS group, ROS was 29 707 cps with significant difference in comparison with the control group (P < 0.05). Significantly higher salivary nitric oxide (145.7 μmol) and nitrite (141.0 μmol) levels were found in OLP patients in comparison with control group (P < 0.05). Increases in nitric oxide and C-reactive protein were found in the saliva of OLP patients in comparison with BMS and control patients. Further studies are required to confirm these findings. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ethylene, nitric oxide and haemoglobins in plant tolerance to flooding

DEFF Research Database (Denmark)

Mur, Luis A J; Gupta, Kapuganti J; Chakraborty, U

2015-01-01

-tolerant species Rumex palustris and the model plant Arabidopsis thaliana have been extensively exploited to reveal some key molecular events. Our groups have recently demonstrated that nitric oxide (NO) triggers the biosynthesis of ethylene during stress and that NO plays key roles in PCD and the hyponastic......As much as 12% of the world's soils may suffer excess water so that flooding is a major limiting factor on crop production in many areas. Plants attempt to deal with submergence by forming root aerenchyma to facilitate oxygen diffusion from the shoot to the root, initiating a hyponastic response....... This chapter will detail our understanding of the roles of ethylene, NO and haemoglobin in flooding stress....

Novel approaches to improving endothelium-dependent nitric oxide-mediated vasodilatation

DEFF Research Database (Denmark)

Simonsen, Ulf; Rodriguez-Rodriguez, Rosalia; Dalsgaard, Thomas

2009-01-01

Endothelial dysfunction, which is defined by decreased endothelium-dependent vasodilatation, is associated with an increased number of cardiovascular events. Nitric oxide (NO) bioavailability is reduced by altered endothelial signal transduction or increased formation of radical oxygen species...... reacting with NO. Endothelial dysfunction is therapeutically reversible and physical exercise, calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists improve flow-evoked endothelium-dependent vasodilation in patients with hypertension and diabetes. We have...... the endothelial signal transduction pathways involved in vasorelaxation and NO release induced by an olive oil component, oleanolic acid, and (3) investigated the role of calcium-activated K channels in the release of NO induced by receptor activation. Tempol increases endothelium-dependent vasodilatation...

Resveratrol and Endothelial Nitric Oxide

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Ning Xia

2014-10-01

Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

International Nuclear Information System (INIS)

Liu Jing; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

2007-01-01

Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation

Absorption and oxidation of no in ionic liquids

DEFF Research Database (Denmark)

2013-01-01

The present invention concerns the absorption and in situ oxidation of nitric oxide (NO) in the presence of water and oxygen in ionic liquid compositions at ambient temperature.......The present invention concerns the absorption and in situ oxidation of nitric oxide (NO) in the presence of water and oxygen in ionic liquid compositions at ambient temperature....

Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-Nitro-L-arginine induces cortical spreading ischemia when K+0+ is increased in the subarachnoid space

DEFF Research Database (Denmark)

Dreier, J.P.; Körner, K.; Ebert, Nathalie

1998-01-01

Cerebral blood flow, nitric oxide, potassium, spreading depression, vasospasm, migraine, migrainous stroke, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)......Cerebral blood flow, nitric oxide, potassium, spreading depression, vasospasm, migraine, migrainous stroke, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)...

Inorganic Nitrate Promotes the Browning of White Adipose Tissue through the Nitrate-Nitrite-Nitric Oxide Pathway

Science.gov (United States)

Roberts, Lee D; Ashmore, Tom; Kotwica, Aleksandra O; Murfitt, Steven A; Fernandez, Bernadette O; Feelisch, Martin; Griffin, Julian L

2015-01-01

Inorganic nitrate was once considered an oxidation end-product of nitric oxide metabolism with little biological activity. However, recent studies have demonstrated that dietary nitrate can modulate mitochondrial function in man and is effective in reversing features of the metabolic syndrome in mice. Using a combined histological, metabolomics, and transcriptional and protein analysis approach we mechanistically define that nitrate not only increases the expression of thermogenic genes in brown-adipose tissue but also induces the expression of brown adipocyte-specific genes and proteins in white adipose tissue, substantially increasing oxygen consumption and fatty acid β-oxidation in adipocytes. Nitrate induces these phenotypic changes through a mechanism distinct from known physiological small molecule activators of browning, the recently identified nitrate-nitrite-nitric oxide pathway. The nitrate-induced browning effect was enhanced in hypoxia, a serious co-morbidity affecting white adipose tissue in obese individuals, and corrected impaired brown adipocyte-specific gene expression in white adipose tissue in a murine model of obesity. Since resulting beige/brite cells exhibit anti-obesity and anti-diabetic effects, nitrate may be an effective means of inducing the browning response in adipose tissue to treat the metabolic syndrome. PMID:25249574

Continuous determination of nitric oxide and nitrogen dioxide in the atmosphere

Energy Technology Data Exchange (ETDEWEB)

Yanagisawa, S; Yamate, N; Mitsuzawa, S; Mori, M

1966-10-01

Continuous determinations of nitric oxide and nitrogen dioxide in that atmospheric air by the use of a modified Saltzman reagent is described. Measurement was made intermittently, once every 30 min., by an automatic continuous analyzer equipped with a single-path colorimeter. The response of the analyzer was obtained as an average of the concentration of nitrogen oxides over a period of 25 min. Two bubblers were used for absorbing nitrogen oxides into the modified Saltzman reagent, whose transmittance was measured for the determination. One bubbler was designed to absorb nitrogen dioxide, and the other, nitric oxide plus nitrogen dioxide after the oxidation of the nitric oxide by permanganate. The oxidizing efficiency of the permanganate was 96-100%. The acetic acid in the Saltzman reagent was replaced with n-propyl alcohol in the modified Saltzman reagent; the spontaneous coloration and corrosive quality of the reagent was decreased by this substitution. The concentration of nitric oxide was obtained from the difference between the two responses of the analyzer, while the concentration of nitrogen dioxide could be read directly from the indication of the recorder. The transmittance ratio method was applied to the measurements, accurate determinations were possible, even at high blank values. Therefore, the reagent was used repeatedly by cycling it on the basis of measuring the difference in the coloration of the reagent before and after the absorption of nitrogen oxides. The analyzer could be used for a long period without changing the reagent.

High-Resolution Electron Energy Loss Studies of Oxygen, Hydrogen, Nitrogen, Nitric Oxide, and Nitrous Oxide Adsorption on Germanium Surfaces.

Science.gov (United States)

Entringer, Anthony G.

The first high resolution electron energy loss spectroscopy (HREELS) studies of the oxidation and nitridation of germanium surfaces are reported. Both single crystal Ge(111) and disordered surfaces were studied. Surfaces were exposed to H, O_2, NO, N _2O, and N, after cleaning in ultra-high vacuum. The Ge surfaces were found to be non-reactive to molecular hydrogen (H_2) at room temperature. Exposure to atomic hydrogen (H) resulted hydrogen adsorption as demonstrated by the presence of Ge-H vibrational modes. The HREEL spectrum of the native oxide of Ge characteristic of nu -GeO_2 was obtained by heating the oxide to 200^circC. Three peaks were observed at 33, 62, and 106 meV for molecular oxygen (O_2) adsorbed on clean Ge(111) at room temperature. These peaks are indicative of dissociative bonding and a dominant Ge-O-Ge bridge structure. Subsequent hydrogen exposure resulted in a shift of the Ge-H stretch from its isolated value of 247 meV to 267 meV, indicative of a dominant +3 oxidation state. A high density of dangling bonds and defects and deeper oxygen penetration at the amorphous Ge surface result in a dilute bridge structure with a predominant +1 oxidation state for similar exposures. Molecules of N_2O decompose at the surfaces to desorbed N_2 molecules and chemisorbed oxygen atoms. In contrast, both oxygen and nitrogen are detected at the surfaces following exposure to NO molecules. Both NO and N_2O appear to dissociate and bond at the top surface layer. Molecular nitrogen (N_2) does not react with the Ge surfaces, however, a precursor Ge nitride is observed at room temperature following exposure to nitrogen atoms and ions. Removal of oxygen by heating of the NO-exposed surface to 550^circC enabled the identification of the Ge-N vibrational modes. These modes show a structure similar to that of germanium nitride. This spectrum is also identical to that of the N-exposed surface heated to 550^circC. Surface phonon modes of the narrow-gap semiconducting

Endothelial nitric oxide synthase gene polymorphisms associated ...

African Journals Online (AJOL)

STORAGESEVER

2010-05-24

May 24, 2010 ... chronic periodontitis (CP), 31 with gingivitis (G) and 50 healthy controls. Probing depth ..... Periodontal disease in pregnancy I. Prevalence and severity. ... endothelial nitric oxide synthase gene in premenopausal women with.

Studies on nitric oxide removal in simulated gas compositions under plasma-dielectric/catalytic discharges

International Nuclear Information System (INIS)

Rajanikanth, B.S.; Rout, Satyabrata

2001-01-01

Application of pulsed electrical discharges for gas cleaning is gaining prominence, mainly from the energy consideration point of view. This present paper presents recent work on applying the electrical discharge plasma technology for treating gaseous pollutants, in general, and nitric oxide, in particular, as this is one of the major contributors to air pollution. The present work focuses attention on pulsed electrical discharge technique for nitric oxide removal from simulated gas compositions and study of effect of packed dielectric pellets, with and without a coating of catalyst, on the removal process. Experiments were conducted in a cylindrical corona reactor energized by repetitive high voltage pulses. The effects of various parameters, viz. pulse voltage magnitude, pulse frequency, initial nitric oxide concentration and gas mixture composition on nitric oxide removal efficiency, are discussed. When the reactors were filled with different dielectric pellets like, barium titanate, alumina, and alumina coated with palladium catalyst, the improvement in nitric oxide removal efficiency is studied and discussed. The power dissipated in the reactor and the energy consumed per nitric oxide molecule removed was calculated. Further results and comparative study of various cases are presented in the paper

The endogenous nitric oxide mediates selenium-induced phytotoxicity by promoting ROS generation in Brassica rapa.

Directory of Open Access Journals (Sweden)

Yi Chen

Full Text Available Selenium (Se is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO in the root of Brassica rapa under Se(IV stress. Se(IV-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR- and nitric oxide synthase (NOS-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.

Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

Science.gov (United States)

Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

Real-time monitoring of nitric oxide (NO) and pO2 levels under ischemic conditions associated with small bowel ischemia/reperfusion injury using selective electrodes for NO and oxygen molecules.

Science.gov (United States)

Watanabe, T; Owada, S; Kobayashi, H; Ishiuchi, A; Nakano, H; Asakuta, T; Shimamura, T; Asano, T; Koizumi, S; Jinnouchi, Y; Katayama, M; Kamibayasi, M; Murakami, E; Otsubo, T

2007-12-01

The present study demonstrated the feasibility of monitoring nitric oxide (NO) and pO2 levels under ischemic conditions associated with small bowel ischemia/reperfusion (I/R) injury through the use of selective electrodes for NO and oxygen molecules. NO levels gradually increased during ischemia. When reperfusion was started, the NO level decreased suddenly and returned to pre-ischemia values within 10 minutes. After clamping, pO2 decreased rapidly. When reperfusion was started, pO2 increased suddenly, returning to pre-ischemia values within 10 minutes. We concluded that it is feasible to monitor NO and pO2 levels under ischemic conditions of small bowel I/R injury through the use of electrodes selective for NO and oxygen molecules.

Preparation and use of nitrogen (2) oxide of special purity for production of oxygen and nitrogen isotopes

International Nuclear Information System (INIS)

Polevoj, A.S.

1989-01-01

Problems related with production of oxygen and nitrogen isotopes by means of low-temperature rectification of nitrogen (2) oxide are analyzed. Special attention, in particular, is payed to the techniques of synthesis and high purification of initial NO, utilization of waste flows formed during isotope separation. Ways to affect the initial isotope composition of nitrogen oxide and the rate of its homogeneous-isotope exchange, which provide for possibility of simultaneous production of oxygen and nitrogen isotopes by means of NO rectification, are considered. Description of a new technique for high purification of nitrogen oxide, prepared at decomposition of nitric acid by sulfurous anhydride, suggested by the author is presented

Interactions between cytokines and nitric oxide.

Science.gov (United States)

Liew, F Y

1995-01-01

There is now an impressive range of evidence supporting the important role of cytokines in sleep regulation (see Krueger et al., 1995; De Simoni et al., 1995). It has also been reported that inhibition of nitric oxide (NO) synthesis suppresses sleep in rabbits (Kapás et al., 1994). This is not surprising, since NO is closely involved in neurotransmission (Garthwaite, 1991; Schuman and Madison, 1994) and cytokines are the major inducers of NO synthesis (Hibbs et al., 1990). Further, it is now clear that NO plays an important role in modulating immune responses, possibly through the differential regulation of cytokine synthesis (Taylor-Robinson et al., 1994). In this article, I will provide evidence for the interactions between cytokines and nitric oxide, and discuss their implications in the regulation of immune responses. I shall illustrate these mainly with results from my coworkers and I, from our laboratory rather than attempting an exhaustive review of the subject.

Vascular nitric oxide: Beyond eNOS

Directory of Open Access Journals (Sweden)

Yingzi Zhao

2015-10-01

Full Text Available As the first discovered gaseous signaling molecule, nitric oxide (NO affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC to produce cyclic guanosine monophosphate (cGMP, although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA or production of cyclic inosine monophosphate (cIMP] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis.

Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

DEFF Research Database (Denmark)

Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina

2000-01-01

We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caused...... a strong increase in NO synthesis that was not seen after parasympathetic stimulation with acetylcholine. In rat parotid acinar cells, we furthermore investigated to which extent the NOS activity was dependent on the intracellular free Ca2+ concentration ([Ca2+]i) by simultaneously measuring NO synthesis...

A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks

DEFF Research Database (Denmark)

Thomsen, L L; Kruuse, C; Iversen, Helle Klingenberg

1994-01-01

Supersensitivity to induction of headache and arterial dilatation by a donor of nitric oxide (nitroglycerin) has recently been demonstrated in migraine sufferers. The aims of the present study were to examine whether the nitric oxide donor nitroglycerin may induce a typical migraine attack......, to exclude placebo-related effects and to describe the relation between middle cerebral artery dilatation and provoked migraine. Nitroglycerin (0.5 μg/kg/min for 20 min) or placebo was infused into 12 migraine patients in a double-blind cross-over trial. Blood velocity in the middle cerebral artery...

Chemical kinetic models for combustion of hydrocarbons and formation of nitric oxide

Science.gov (United States)

Jachimowski, C. J.; Wilson, C. H.

1980-01-01

The formation of nitrogen oxides NOx during combustion of methane, propane, and a jet fuel, JP-4, was investigated in a jet stirred combustor. The results of the experiments were interpreted using reaction models in which the nitric oxide (NO) forming reactions were coupled to the appropriate hydrocarbon combustion reaction mechanisms. Comparison between the experimental data and the model predictions reveals that the CH + N2 reaction process has a significant effect on NO formation especially in stoichiometric and fuel rich mixtures. Reaction models were assembled that predicted nitric oxide levels that were in reasonable agreement with the jet stirred combustor data and with data obtained from a high pressure (5.9 atm (0.6 MPa)), prevaporized, premixed, flame tube type combustor. The results also suggested that the behavior of hydrocarbon mixtures, like JP-4, may not be significantly different from that of pure hydrocarbons. Application of the propane combustion and nitric oxide formation model to the analysis of NOx emission data reported for various aircraft gas turbines showed the contribution of the various nitric oxide forming processes to the total NOx formed.

Nitric Oxide PLIF Measurements in the Hypersonic Materials Environmental Test System (HYMETS)

Science.gov (United States)

Inman, Jennifer A.; Bathel, Brett F.; Johansen, Craig T.; Danehy, Paul M.; Jones, Stephen B.; Gragg, Jeffrey G.; Splinter, Scott C.; McRae, Colin D.

2013-01-01

Planar laser-induced fluorescence (PLIF) of naturally occurring nitric oxide (NO) has been used to obtain instantaneous flow visualization images, and to make both radial and axial velocity measurements in the HYMETS (Hypersonic Materials Environmental Test System) 400 kW arc-heated wind tunnel at NASA Langley Research Center. This represents the first application of NO PLIF flow visualization in HYMETS. Results are presented at selected facility run conditions, including some in a simulated Earth atmosphere (75% nitrogen, 20% oxygen, 5% argon) and others in a simulated Martian atmosphere (71% carbon dioxide, 24% nitrogen, 5% argon), for specific bulk enthalpies ranging from 6.5 MJ/kg to 18.4 MJ/kg. Flow visualization images reveal the presence of large scale unsteady flow structures, and indicate nitric oxide fluorescence signal over more than 70% of the core flow for specific bulk enthalpies below about 11 MJ/kg, but over less than 10% of the core flow for specific bulk enthalpies above about 16 MJ/kg. Axial velocimetry was performed using molecular tagging velocimetry (MTV). Axial velocities of about 3 km/s were measured along the centerline. Radial velocimetry was performed by scanning the wavelength of the narrowband laser and analyzing the resulting Doppler shift. Radial velocities of +/- 0.5 km/s were measured.

Nitric oxide as a mediator of gastrointestinal mucosal injury?—Say it ain't so

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Paul Kubes

1995-01-01

Full Text Available Nitric oxide has been suggested as a contributor to tissue injury in various experimental models of gastrointestinal inflammation. However, there is overwhelming evidence that nitric oxide is one of the most important mediators of mucosal defence, influencing such factors as mucus secretion, mucosal blood flow, ulcer repair and the activity of a variety of mucosal immunocytes. Nitric oxide has the capacity to down-regulate inflammatory responses in the gastrointestinal tract, to scavenge various free radical species and to protect the mucosa from injury induced by topical irritants. Moreover, questions can be raised regarding the evidence purported to support a role for nitric oxide in producing tissue injury. In this review, we provide an overview of the evidence supporting a role for nitric oxide in protecting the gastrointestinal tract from injury.

Pentose Phosphate Shunt Modulates Reactive Oxygen Species and Nitric Oxide Production Controlling Trypanosoma cruzi in Macrophages

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Sue-jie Koo

2018-02-01

Full Text Available Metabolism provides substrates for reactive oxygen species (ROS and nitric oxide (NO generation, which are a part of the macrophage (Mφ anti-microbial response. Mφs infected with Trypanosoma cruzi (Tc produce insufficient levels of oxidative species and lower levels of glycolysis compared to classical Mφs. How Mφs fail to elicit a potent ROS/NO response during infection and its link to glycolysis is unknown. Herein, we evaluated for ROS, NO, and cytokine production in the presence of metabolic modulators of glycolysis and the Krebs cycle. Metabolic status was analyzed by Seahorse Flux Analyzer and mass spectrometry and validated by RNAi. Tc infection of RAW264.7 or bone marrow-derived Mφs elicited a substantial increase in peroxisome proliferator-activated receptor (PPAR-α expression and pro-inflammatory cytokine release, and moderate levels of ROS/NO by 18 h. Interferon (IFN-γ addition enhanced the Tc-induced ROS/NO release and shut down mitochondrial respiration to the levels noted in classical Mφs. Inhibition of PPAR-α attenuated the ROS/NO response and was insufficient for complete metabolic shift. Deprivation of glucose and inhibition of pyruvate transport showed that Krebs cycle and glycolysis support ROS/NO generation in Tc + IFN-γ stimulated Mφs. Metabolic profiling and RNAi studies showed that glycolysis-pentose phosphate pathway (PPP at 6-phosphogluconate dehydrogenase was essential for ROS/NO response and control of parasite replication in Mφ. We conclude that IFN-γ, but not inhibition of PPAR-α, supports metabolic upregulation of glycolytic-PPP for eliciting potent ROS/NO response in Tc-infected Mφs. Chemical analogs enhancing the glucose-PPP will be beneficial in controlling Tc replication and dissemination by Mφs.

The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii

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Talman W.T.

1997-01-01

Full Text Available Considerable evidence suggests that nitroxidergic mechanisms in the nucleus tractus solitarii (NTS participate in cardiovascular reflex control. Much of that evidence, being based on responses to nitric oxide precursors or inhibitors of nitric oxide synthesis, has been indirect and circumstantial. We sought to directly determine cardiovascular responses to nitric oxide donors microinjected into the NTS and to determine if traditional receptor mechanisms might account for responses to certain of these donors in the central nervous system. Anesthetized adult Sprague Dawley rats that were instrumented for recording arterial pressure and heart rate were used in the physiological studies. Microinjection of nitric oxide itself into the NTS did not produce any cardiovascular responses and injection of sodium nitroprusside elicited minimal depressor responses. The S-nitrosothiols, S-nitrosoglutathione (GSNO, S-nitrosoacetylpenicillamine (SNAP, and S-nitroso-D-cysteine (D-SNC produced no significant cardiovascular responses while injection of S-nitroso-L-cysteine (L-SNC elicited brisk, dose-dependent depressor and bradycardic responses. In contrast, injection of glyceryl trinitrate elicited minimal pressor responses without associated changes in heart rate. It is unlikely that the responses to L-SNC were dependent on release of nitric oxide in that 1 the responses were not affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis prior to injection of L-SNC and 2 L- and D-SNC released identical amounts of nitric oxide when exposed to brain tissue homogenates. Although GSNO did not independently affect blood pressure, its injection attenuated responses to subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested that in rat brain synaptosomes there is a saturable binding site for GSNO that is displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine, not nitric oxide, may be an

Glufosinate ammonium stimulates nitric oxide production through N-methyl D-aspartate receptors in rat cerebellum.

Science.gov (United States)

Nakaki, T; Mishima, A; Suzuki, E; Shintani, F; Fujii, T

2000-09-01

Glufosinate ammonium, a structural analogue of glutamate, is an active herbicidal ingredient. The neuronal activities of this compound were investigated by use of a microdialysis system that allowed us to measure nitric oxide production in the rat cerebellum in vivo. Kainate (0.3-30 nmol/10 microliter), N-methyl-D-aspartate (NMDA) (3-300 nmol/10 microliter) and glufosinate ammonium (30-3000 nmol/10 microliter), which were administered through the microdialysis probe at a rate of 1 microliter/min for 10 min, stimulated nitric oxide production. The glufosinate ammonium-elicited increase in nitric oxide production was suppressed by an inhibitor of nitric oxide synthase and was antagonized by NMDA receptor antagonists, but not by a kainate/(+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist. These results suggest that glufosinate ammonium stimulates nitric oxide production through NMDA receptors.

Weaning of inhaled nitric oxide: is there a best strategy?

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Anita M. Ware

2015-04-01

Full Text Available Background: Inhaled nitric oxide (iNO has been used in the treatment of pulmonary hypertension in neonates for many years. iNO was approved by the FDA in 1999 for hypoxic respiratory failure (HRF in term and near term infants, defined as > 34 weeks gestational age (GA. iNO is used for persistent pulmonary hypertension of the newborn (PPHN, secondary pulmonary hypertension caused by congenital heart disease (CHD, congenital diaphragmatic hernia (CDH, meconium aspiration syndrome (MAS, pneumonia, respiratory distress syndrome (RDS, and other pathologies. iNO has its effect locally on the pulmonary vasculature and has been studied extensively regarding its effect on morbidities such as: need for extracorporeal membrane oxygenation (ECMO, oxygen requirements, and mechanical ventilatory support. However, protocols for weaning iNO and for the duration of iNO weaning have not been studied extensively. It has been shown that an abrupt discontinuation leads to rebound pulmonary hypertension.Methods: Electronic literature search and review of published articles on the use of iNO in the neonate.Results: Electronic databases including Medline and PubMed were searched from the years 1995-2015, using the keywords "iNO", "nitric oxide", "neonate", and "weaning nitric oxide." This search revealed 2,124 articles. Articles were determined to be eligible for review if they included a specific protocol for weaning iNO, and were published in English. 16 articles with specific protocols for iNO weaning have been identified and reviewed. The studies had enrolled a total of 1,735 neonates either at term either preterm and with a mean birth weight of 3.3 kg (± 2 kg. Main diagnoses included MAS, CHD (total anomalous pulmonary venous return [TAPVR], d-transposition of the great vessels [DTGV], atrial septal defect [ASD], pulmonary atresia [PA], hypoplastic left heart syndrome [HLH], pneumonia, RDS, hyaline membrane disease (HMD, PPHN, CDH, sepsis, pulmonary hypoplasia

Arylboronate ester based diazeniumdiolates (BORO/NO), a class of hydrogen peroxide inducible nitric oxide (NO) donors.

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Dharmaraja, Allimuthu T; Ravikumar, Govindan; Chakrapani, Harinath

2014-05-16

Here, we report the design, synthesis, and evaluation of arylboronate ester based diazeniumdiolates (BORO/NO), a class of nitric oxide (NO) donors activated by hydrogen peroxide (H2O2), a reactive oxygen species (ROS), to generate NO. We provide evidence for the NO donors' ability to permeate bacteria to produce NO when exposed to H2O2 supporting possible applications for BORO/NO to study molecular mechanisms of NO generation in response to elevated ROS.

Increase of hepatic nitric oxide levels in a nutritional model of fatty ...

African Journals Online (AJOL)

GREGORY

2010-08-30

Aug 30, 2010 ... (MDA) and protein carbonyl (PC), and also nitric oxide (NO) in over fed broiler breeder hens, 198 hens. (30 weeks old) .... The total protein in the liver tissue was determined by a method ... Table 1. Egg production and LHS in broiler breeder hens .... trations of nitric oxide metabolites (nitrates-nitrites) in rat.

Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

International Nuclear Information System (INIS)

Kumagai, Yoshito; Pi Jingbo

2004-01-01

Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

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Giovanna Romano

Full Text Available Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms.

Hepatic Flavin-Containing Monooxygenase 3 Enzyme Suppressed by Type 1 Allergy-Produced Nitric Oxide.

Science.gov (United States)

Tanino, Tadatoshi; Bando, Toru; Komada, Akira; Nojiri, Yukie; Okada, Yuna; Ueda, Yukari; Sakurai, Eiichi

2017-11-01

Flavin-containing monooxygenases (FMOs) are major mammalian non-cytochrome P450 oxidative enzymes. T helper 2 cell-activated allergic diseases produce excess levels of nitric oxide (NO) that modify the functions of proteins. However, it remains unclear whether allergy-induced NO affects the pharmacokinetics of drugs metabolized by FMOs. This study investigated alterations of hepatic microsomal FMO1 and FMO3 activities in type 1 allergic mice and further examined the interaction of FMO1 and FMO3 with allergy-induced NO. Imipramine (IMP; FMO1 substrate) N- oxidation activity was not altered in allergic mice with high serum NO and immunoglobulin E levels. At 7 days after primary sensitization (PS7) or secondary sensitization (SS7), benzydamine (BDZ; FMO1 and FMO3 substrate) N- oxygenation was significantly decreased to 70% of individual controls. The expression levels of FMO1 and FMO3 proteins were not significantly changed in the sensitized mice. Hepatic inducible NO synthase (iNOS) mRNA level increased 5-fold and 15-fold in PS7 and SS7 mice, respectively, and hepatic tumor necrosis factor- α levels were greatly enhanced. When a selective iNOS inhibitor was injected into allergic mice, serum NO levels and BDZ N- oxygenation activity returned to control levels. NO directly suppressed BDZ N- oxygenation, which was probably related to FMO3-dependent metabolism in comparison with IMP N- oxidation. In hepatic microsomes from PS7 and SS7 mice, the suppression of BDZ N- oxygenation was restored by ascorbate. Therefore, type 1 allergic mice had differentially suppressed FMO3-dependent BDZ N- oxygenation. The suppression of FMO3 metabolism related to reversible S- nitrosyl modifications of iNOS-derived NO. NO is expected to alter FMO3-metabolic capacity-limited drug pharmacokinetics in humans. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Acute Respiratory Distress Syndrome (ARDS After Nitric Acid Inhalation

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Gülay Kır

2014-12-01

Full Text Available Lung injury resulting from inhalation of chemical products continues to be associated with high morbidity and mortality. Concentrated nitric acids are also extremely corrosive fuming chemical liquids. Fumes of nitric acid (HNO3 and various oxides of nitrogen such as nitric oxide (NO and nitrogen dioxide (NO2 may cause fatal illnesses such as severe pulmonary edema and acute respiratory distress syndrome (ARDS when inhaled. Intensive respiratory management including mechanical ventilation with positive end expiratory pressure (PEEP, inverse ratio ventilation, replacement of surfactant and extracorporeal membrane oxygenation (ECMO, steroids and n-acetylcysteine (NAC may improve survival. In this case report we present the diagnosis and successful treatment of a 57 years old male patient who developed ARDS following pulmonary edema due to nitric acid fumes inhalation.

Modulation of cholinergic airway reactivity and nitric oxide production by endogenous arginase activity

NARCIS (Netherlands)

Meurs, Herman; Hamer, M.A M; Pethe, S; Vadon-Le Goff, S; Boucher, J.-L; Zaagsma, Hans

1 Cholinergic airway constriction is functionally antagonized by agonist-induced constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO). Since cNOS and arginase, which hydrolyzes L-arginine to L-ornithine and urea, use L-arginine as a common substrate, competition between both enzymes

Nitric-phosphoric acid oxidation of organic waste materials

International Nuclear Information System (INIS)

Pierce, R.A.; Smith, J.R.

1995-01-01

A wet chemical oxidation technology has been developed to address issues facing defense-related facilities, private industry, and small-volume generators such as university and medical laboratories. Initially tested to destroy and decontaminate a heterogenous mixture of radioactive-contaminated solid waste, the technology can also remediate other hazardous waste forms. The process, unique to Savannah River, offers a valuable alternative to incineration and other high-temperature or high-pressure oxidation processes. The process uses nitric acid in phosphoric acid; phosphoric acid allows nitric acid to be retained in solution well above its normal boiling point. The reaction converts organics to carbon dioxide and water, and generates NO x vapors which can be recycled using air and water. Oxidation is complete in one to three hours. In previous studies, many organic compounds were completely oxidized, within experimental error, at atmospheric pressure below 180 degrees C; more stable compounds were decomposed at 200 degrees C and 170 kPa. Recent studies have evaluated processing parameters and potential throughputs for three primary compounds: EDTA, polyethylene, and cellulose. The study of polyvinylchloride oxidation is incomplete at this time

A possible mechanism for transpupillary thermotherapy: nitric-oxide-related cellular damage.

Science.gov (United States)

Ozdek, Sengul; Urgancioglu, Berrak; Turkcu, Ummuhani Ozel; Bilgihan, Ayse

2007-08-01

To determine the oxidative stress markers on rabbit vitreous following transpupillary thermotherapy (TTT) application. The pigmented rabbit eyes were divided into 3 groups, each containing 6 eyes. Group 1 was used as a control group. Twelve eyes underwent TTT with a power of 250 mW (group 2) and 800 mW (group 3), with a diameter of 3000 microm and duration of 60 s; 24 h after laser application, vitreous samples were collected. Nitric oxide (NO) and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were determined in all groups. NO levels were statistically significantly higher in all groups when compared with the control group (p 0.05). Our results support the hypothesis that TTT application induces NO synthesis, which may lead to occlusion at choroidal neovessels. Because of the nonsignificantly increased levels of MDA and decrease of SOD activities there maybe only a weak relation between lipid peroxidation induced by free oxygen radicals and TTT-induced vascular damage.

Nitric oxide levels in the anterior chamber of vitrectomized eyes with silicon oil

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Paulo Escarião

2013-10-01

Full Text Available PURPOSE: To investigate the nitric oxide levels in the anterior chamber of eyes who underwent pars plana vitrectomy (PPV with silicone oil. METHODS: Patients who underwent PPV with silicon oil injection, from february 2005 to august 2007, were selected. Nine patients (nine eyes participated in the study (five women and four men. Nitric oxide concentration was quantified after the aspiration of aqueous humor samples during the procedure of silicon oil removal. Data such as: oil emulsification; presence of oil in the anterior chamber; intraocular pressure and time with silicone oil were evaluated. Values of p <0.05 were considered to be statistically significant. RESULTS: A positive correlation between nitric oxide concentration and time with silicon oil in the vitreous cavity (r=0.799 was observed. The nitric oxide concentration was significantly higher (p=0.02 in patients with silicon oil more than 24 months (0.90µmol/ml ± 0.59, n=3 in the vitreous cavity comparing to patients with less than 24 months (0.19µmol/ml ± 0.10, n=6. CONCLUSION: A positive correlation linking silicone oil time in the vitreous cavity with the nitric oxide concentration in the anterior chamber was observed.

Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of interstitial lung disease and pulmonary hypertension.

Science.gov (United States)

Ruisi, Phillip; Ruisi, Michael

2011-01-01

Carbon monoxide (CO) has been widely recognized as an exogenous poison, although endogenous mechanisms for its formation involve heme-oxygenase (HO) isoforms, more specifically HO-1, in the setting of oxidative stress such as acute respiratory distress syndrome, sepsis, trauma, and nitric oxide use have been studied. In patients with refractory hypoxemia, inhaled nitric oxide (iNO) therapy is used to selectively vasodilate the pulmonary vasculature and improve ventilation-perfusion match. Inhaled nitric oxide is rapidly inactivated on binding to hemoglobin in the formation of nitrosyl- and methemoglobin in the pulmonary vasculature. Hence, inhaled nitric oxide has minimal systemic dissemination. Several experimental design studies involving lab rats have demonstrated increased levels of carboxyhemoglobin and exhaled CO as a result of nitric oxide HO-1 induction.

Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-γ-induced pulmonary inflammation

International Nuclear Information System (INIS)

Zeidler, Patti C.; Millecchia, Lyndell M.; Castranova, Vincent

2004-01-01

Exposure of mice to lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) increases nitric oxide (NO) production, which is proposed to play a role in the resulting pulmonary damage and inflammation. To determine the role of inducible nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT) mice to aspirated LPS + IFN-γ were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-γ (5000 U/mouse) or saline. At 24 or 72 h postexposure, lungs were lavaged with saline and the acellular fluid from the first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN-γ were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-α, and MIP-2, and enhanced AM-CL to the same extent in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however, significant differences were found between WT and iNOS KO mice. iNOS KO mice demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs, LDH, albumin, TNF-α, and MIP-2, and an enhanced AM-CL compared to the WT. These data suggest that the role of iNOS-derived NO in the pulmonary response to LPS + IFN-γ is anti-inflammatory, and this becomes evident over time

Enhancement of vascular targeting by inhibitors of nitric oxide synthase

International Nuclear Information System (INIS)

Davis, Peter D.; Tozer, Gillian M.; Naylor, Matthew A.; Thomson, Peter; Lewis, Gemma; Hill, Sally A.

2002-01-01

Purpose: This study investigates the enhancement of the vascular targeting activity of the tubulin-binding agent combretastatin A4 phosphate (CA4P) by various inhibitors of nitric oxide synthases. Methods and Materials: The syngeneic tumors CaNT and SaS growing in CBA mice were used for this study. Reduction in perfused vascular volume was measured by injection of Hoechst 33342 24 h after drug administration. Necrosis (hematoxylin and eosin stain) was assessed also at 24 h after treatment. Combretastatin A4 phosphate was synthesized by a modification of the published procedure and the nitric oxide synthase inhibitors L-NNA, L-NMMA, L-NIO, L-NIL, S-MTC, S-EIT, AMP, AMT, and L-TC, obtained from commercial sources. Results: A statistically significant augmentation of the reduction in perfused vascular volume by CA4P in the CaNT tumor was observed with L-NNA, AMP, and AMT. An increase in CA4P-induced necrosis in the same tumor achieved significance with L-NNA, L-NMMA, L-NIL, and AMT. CA4P induced little necrosis in the SaS tumor, but combination with the inhibitors L-NNA, L-NMMA, L-NIO, S-EIT, and L-TC was effective. Conclusions: Augmentation of CA4P activity by nitric oxide synthase inhibitors of different structural classes supports a nitric oxide-related mechanism for this effect. L-NNA was the most effective inhibitor studied

Kinetics of Several Oxygen-Containing Carbon-Centered Free Radical Reactions with Nitric Oxide.

Science.gov (United States)

Rissanen, Matti P; Ihlenborg, Marvin; Pekkanen, Timo T; Timonen, Raimo S

2015-07-16

Kinetics of four carbon-centered, oxygen-containing free radical reactions with nitric oxide (NO) were investigated as a function of temperature at a few Torr pressure of helium, employing flow tube reactors coupled to a laser-photolysis/resonance-gas-discharge-lamp photoionization mass spectrometer (LP-RPIMS). Rate coefficients were directly determined from radical (R) decay signals under pseudo-first-order conditions ([R]0 ≪ [NO]). The obtained rate coefficients showed negative temperature dependences, typical for a radical-radical association process, and can be represented by the following parametrizations (all in units of cm(3) molecule(-1) s(-1)): k(CH2OH + NO) = (4.76 × 10(-21)) × (T/300 K)(15.92) × exp[50700/(RT)] (T = 266-363 K, p = 0.79-3.44 Torr); k(CH3CHOH + NO) = (1.27 × 10(-16)) × (T/300 K)(6.81) × exp[28700/(RT)] (T = 241-363 K, p = 0.52-3.43 Torr); k(CH3OCH2 + NO) = (3.58 ± 0.12) × 10(-12) × (T/300 K)(-3.17±0.14) (T = 221-363 K, p = 0.50-0.80 Torr); k(T)3 = 9.62 × 10(-11) × (T/300 K)(-5.99) × exp[-7100/(RT)] (T = 221-473 K, p = 1.41-2.95 Torr), with the uncertainties given as standard errors of the fits and the overall uncertainties estimated as ±20%. The rate of CH3OCH2 + NO reaction was measured in two density ranges due to its observed considerable pressure dependence, which was not found in the studied hydroxyalkyl reactions. In addition, the CH3CO + NO rate coefficient was determined at two temperatures resulting in k298K(CH3CO + NO) = (5.6 ± 2.8) × 10(-13) cm(3) molecule(-1) s(-1). No products were found during these experiments, reasons for which are briefly discussed.

Sensing nitric oxide with a carbon nanofiber paste electrode modified with a CTAB and nafion composite

International Nuclear Information System (INIS)

Zheng, Dongyun; Liu, Xiaojun; Zhu, Shanying; Cao, Huimin; Chen, Yaguang; Hu, Shengshui

2015-01-01

We describe an electrochemical sensor for nitric oxide that was obtained by modifying the surface of a nanofiber carbon paste microelectrode with a film composed of hexadecyl trimethylammonium bromide and nafion. The modified microelectrode displays excellent catalytic activity in the electrochemical oxidation of nitric oxide. The mechanism was studied by scanning electron microscopy and cyclic voltammetry. Under optimal conditions, the oxidation peak current at a working voltage of 0.75 V (vs. SCE) is related to the concentration of nitric oxide in the 2 nM to 0.2 mM range, and the detection limit is as low as 2 nM (at an S/N ratio of 3). The sensor was successfully applied to the determination of nitric oxide released from mouse hepatocytes. (author)

The NADPH oxidase inhibitor apocynin induces nitric oxide synthesis via oxidative stress

International Nuclear Information System (INIS)

Riganti, Chiara; Costamagna, Costanzo; Doublier, Sophie; Miraglia, Erica; Polimeni, Manuela; Bosia, Amalia; Ghigo, Dario

2008-01-01

We have recently shown that apocynin elicits an oxidative stress in N11 mouse glial cells and other cell types. Here we report that apocynin increased the accumulation of nitrite, the stable derivative of nitric oxide (NO), in the extracellular medium of N11 cell cultures, and the NO synthase (NOS) activity in cell lysates. The increased synthesis of NO was associated with increased expression of inducible NOS (iNOS) mRNA, increased nuclear translocation of the redox-sensitive transcription factor NF-κB and decreased intracellular level of its inhibitor IkBα. These effects, accompanied by increased production of H 2 O 2 , were very similar to those observed after incubation with bacterial lipopolysaccharide (LPS) and were inhibited by catalase. These results suggest that apocynin, similarly to LPS, induces increased NO synthesis by eliciting a generation of reactive oxygen species (ROS), which in turn causes NF-κB activation and increased expression of iNOS. Therefore, the increased bioavailability of NO reported in the literature after in vivo or in vitro treatments with apocynin might depend, at least partly, on the drug-elicited induction of iNOS, and not only on the inhibition of NADPH oxidase and the subsequent decreased scavenging of NO by oxidase-derived ROS, as it is often supposed

Expression of inducible nitric oxide synthase, caspase-3 and production of reactive oxygen intermediate on endothelial cells culture (HUVECs treated with P. falciparum infected erythrocytes and tumour necrosis factor-α

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Loeki E. Fitri

2006-09-01

Full Text Available Cytoadherence of P. falciparum infected erythrocytes on endothelial cells is a key factor in development of severe malaria. This process may associated with the activation of local immune that was enhanced by tumour necrosis factor-α (TNF-α. This study was conducted to see the influence of P.falciparum infected erythrocytes cytoadherence and TNF-α treatment in inducing endothelial cells activation in vitro. inducible nitric oxide synthase (iNOS and caspase-3 expression, also reactive oxygen intermediate (ROI production were used as parameters. An Experimental laboratory study had been done to observe endothelial cells activation (HUVECs after treatment with TNF-α for 20 hours or P. falciparum infected erythrocytes for 1 hour or both of them. Normal endothelial cells culture had been used as a control. Using immunocytochemistry local immune activation of endothelial cells was determined by iNOS and caspase-3 expression. Nitro Blue Tetrazolium reduction-assay was conducted to see the ROI production semi quantitatively. inducible nitric oxide synthase expression only found on endothelial cells culture treated with P. falciparum infected erythrocytes or both P. falciparum infected erythrocytes and TNF-α. Caspase-3 expression found slightly on normal endothelial cells culture. This expression increased significantly on endothelial cells culture treated with both P.falciparum infected erythrocytes and TNF-α (p=0.000. The normal endothelial cells release low level of ROI in the presence of non-specific trigger, PMA. In the presence of P. falciparum infected erythrocytes or TNF-α or both of them, some cells showed medium to high levels of ROI. Cytoadherence of P. falciparum infected erythrocytes and TNF α treatment on endothelial cells can induce activation of local immune marked by increase inducible nitric oxide synthase and release of free radicals that cause cell damage. (Med J Indones 2006; 15:151-6 Keywords: P.falciparum ,HUVECs, TNF-α, i

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity.

Science.gov (United States)

Renton, Paul; Green, Brenda; Maddaford, Shawn; Rakhit, Suman; Andrews, John S

2012-03-08

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure-activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, K i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain.

Features of molybdenum disulfide interaction with nitric acid

International Nuclear Information System (INIS)

Chursanov, Yu.V.; Potashnikov, Yu.M.; Rumyantsev, V.K.

1987-01-01

Experiments on studying composition of products of molybdenite concentrate (MoS 2 ) oxidation by HNO 3 solutions were conducted. Molybdenite oxidation was conducted in a glass temperature controlled vessel in absence of oxygen. It was shown that nitrogen (2) oxide represented the final product of molybdenite interaction with nitric acid. The process was accompanied as well by separation of NO 2 and HNO 2 under dynamic conditions, and nitrogen (4) oxide acted as catalyst of oxidation at that

ORIGINAL ARTICLE Relationship between endothelial nitric oxide ...

African Journals Online (AJOL)

salah

The haplotype analysis confirmed ... hand, no consistent association was shown between the two SNPs and SBP or. DBP. ... Endothelial nitric oxide synthase gene polymorphisms and risk of MI .... type (-786T*+894G), the haplotypes ... Tests adjusted for age, BMI, diabetes, current smoking and alcohol consumption.

Endothelial nitric oxide synthase gene polymorphisms associated ...

African Journals Online (AJOL)

Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

Energy Technology Data Exchange (ETDEWEB)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G., E-mail: bipin@amrita.edu

2016-08-15

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

International Nuclear Information System (INIS)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G.

2016-01-01

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

Management of Postoperative Pulmonary Hypertension by Inhaled Nitric Oxide in a Newborn with Congenital Diaphragmatic Hernia

International Nuclear Information System (INIS)

Fettah, N. D.; Dilli, D.; Beken, S.; Zenciroglu, A.; Okumus, N.; Cavusoglu, H.; Ozgur, S.

2014-01-01

Postero-lateral congenital diaphragmatic hernia (CDH) is a life threatening anomaly characterized by diaphragmatic defect and intrathoracic herniation of abdominal viscera. In patients with CDH, the lungs are hypoplastic and persistent pulmonary hypertension develops in most cases. Although, inhaled nitric oxide (iNO) results in a reduction in pulmonary hypertension with improvement in oxygenation, its benefit in the patients with CDH remains controversial. In this report, the authors present successful management of postoperative pulmonary hypertension by iNO in a newborn with CDH. (author)

Caveolin versus calmodulin. Counterbalancing allosteric modulators of endothelial nitric oxide synthase.

Science.gov (United States)

Michel, J B; Feron, O; Sase, K; Prabhakar, P; Michel, T

1997-10-10

Nitric oxide is synthesized in diverse mammalian tissues by a family of calmodulin-dependent nitric oxide synthases. The endothelial isoform of nitric oxide synthase (eNOS) is targeted to the specialized signal-transducing membrane domains termed plasmalemmal caveolae. Caveolin, the principal structural protein in caveolae, interacts with eNOS and leads to enzyme inhibition in a reversible process modulated by Ca2+-calmodulin (Michel, J. B., Feron, O., Sacks, D., and Michel, T. (1997) J. Biol. Chem. 272, 15583-15586). Caveolin also interacts with other structurally distinct signaling proteins via a specific region identified within the caveolin sequence (amino acids 82-101) that appears to subserve the role of a "scaffolding domain." We now report that the co-immunoprecipitation of eNOS with caveolin is completely and specifically blocked by an oligopeptide corresponding to the caveolin scaffolding domain. Peptides corresponding to this domain markedly inhibit nitric oxide synthase activity in endothelial membranes and interact directly with the enzyme to inhibit activity of purified recombinant eNOS expressed in Escherichia coli. The inhibition of purified eNOS by the caveolin scaffolding domain peptide is competitive and completely reversed by Ca2+-calmodulin. These studies establish that caveolin, via its scaffolding domain, directly forms an inhibitory complex with eNOS and suggest that caveolin inhibits eNOS by abrogating the enzyme's activation by calmodulin.

Nitric oxide and TGF-β1 inhibit HNF-4α function in HEPG2 cells

International Nuclear Information System (INIS)

Lucas, Susana de; Lopez-Alcorocho, Juan Manuel; Bartolome, Javier; Carreno, Vicente

2004-01-01

This study analyzes if the profibrogenic factors nitric oxide and transforming growth factor-β1 (TGF-β1) affect hepatocyte nuclear factor-4α (HNF-4α) function. For this purpose, HepG2 cells were treated with TGF-β1 or with a nitric oxide donor to determine mRNA levels of coagulation factor VII and HNF-4α. Treatment effect on factor VII gene promoter was assessed by chloramphenicol acetyl-transferase assays in cells transfected with the pFVII-CAT plasmid. HNF-4α binding and protein levels were determined by gel shift assays and Western blot. TGF-β1 and nitric oxide downregulated factor VII mRNA levels by inhibiting its gene promoter activity. This inhibition is caused by a decrease in the DNA binding of HNF-4α. TGF-β1 induces degradation of HNF-4α in the proteasome while nitric oxide provokes nitrosylation of cysteine residues in this factor. TGF-β1 and nitric oxide inhibit HNF-4α activity. These findings may explain the loss of liver functions that occurs during fibrosis progression

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

Science.gov (United States)

Grassi, S; Pettorossi, V E

2000-01-01

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

Catalytic properties of oxygen adsorbed on NiO-Sm/sub 2/O/sub 3/ binary oxides

Energy Technology Data Exchange (ETDEWEB)

Tadasu, Y.; Niwa, H.; Matsuda, Y.

1978-02-01

Various rare earths were screened as promoters for a nickel oxidation catalyst, and samarium (Sm) was selected for further studies. The activity of a physical mixture of NiO/Sm/sub 2/O/sub 3/ and SiC for the oxidation of 500 ppm nitric oxide with 5% oxygen in nitrogen to nitrogen dioxide at 320/sup 0/C went through a maximum with increasing Sm/sub 2/O/sub 3/ content of the catalyst. The most active catalyst, which contained 3.75% Sm/sub 2/O/sub 3/, was 3.7 times as active as pure nickel oxide. Temperature-programed desorption of oxygen from the catalysts revealed three peaks, ..cap alpha.. at 220/sup 0/-230/sup 0/C ..beta.. at 370/sup 0/-380/sup 0/C, and ..gamma.. at 530/sup 0/-540/sup 0/C, for all catalysts except pure Sm/sub 2/O/sub 3/. The amount of adsorbed oxygen increased with increasing Sm/sub 2/O/sub 3/ content to 3.75%, and then decreased with further Sm/sub 2/O/sub 3/ increases. The catalytic activity was correlated to oxygen in the ..beta..-state. Graphs, spectra, and table.

Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

Science.gov (United States)

Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

2007-09-01

In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

Iron(II) porphyrins induced conversion of nitrite into nitric oxide: A computational study.

Science.gov (United States)

Zhang, Ting Ting; Liu, Yong Dong; Zhong, Ru Gang

2015-09-01

Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed. The results indicate that the pathway of N-bound Fe(II)(P)(NO2) isomer into Fe(III)(P)(NO) and water is similar to that of O-bound isomer into nitric oxide and Fe(III)(P)(OH) in both thermodynamical and dynamical aspects. Based on the initial computational studies of five-coordinate nitrite complexes, the conversion of nitrite into NO mediated by Fe(II)(P)(L) complexes with 14 kinds of proximal ligands was also investigated. Generally, the same conclusion that the pathways of N-bound isomers are similar to those of O-bound isomer was obtained for iron(II) porphyrin with ligands. Different effects of ligands on the reduction reactions were also found. It is notable that the negative proximal ligands can improve reactive abilities of N-nitro-iron(II) porphyrins in the conversion of nitrite into nitric oxide compared to neutral ligands. The findings will be helpful to expand our understanding of the mechanism of nitrite reduction to nitric oxide by iron(II) porphyrins. Copyright © 2015 Elsevier Inc. All rights reserved.

Endothelial nitric oxide synthase polymorphism G298T in ...

Indian Academy of Sciences (India)

Supplementary data: Endothelial nitric oxide synthase polymorphism G298T in association with oxidative DNA damage in coronary atherosclerosis. Rajesh G. Kumar, Mrudula K. Spurthi, Kishore G. Kumar, Sanjib K. Sahu and Surekha H. Rani. J. Genet. 91, 349–352. Table 1. The demographic and clinical data of the CHD ...

Inducible nitric oxide synthase catalyzes ethanol oxidation to α-hydroxyethyl radical and acetaldehyde

International Nuclear Information System (INIS)

Porasuphatana, Supatra; Weaver, John; Rosen, Gerald M.

2006-01-01

The physiologic function of nitric oxide synthases, independent of the isozyme, is well established, metabolizing L-arginine to L-citrulline and nitric oxide (NO). This enzyme can also transfer electrons to O 2 , affording superoxide (O 2 · - ) and hydrogen peroxide (H 2 O 2 ). We have demonstrated that NOS1, in the presence of L-arginine, can biotransform ethanol (EtOH) to α-hydroxyethyl radical (CH 3 ·CHOH). We now report that a competent NOS2 with L-arginine can, like NOS1, oxidize EtOH to CH 3 ·CHOH. Once this free radical is formed, it is metabolized to acetaldehyde as shown by LC-ESI-MS/MS and HPLC analysis. These observations suggest that NOS2 can behave similarly to cytochrome P-450 in the catalysis of acetaldehyde formation from ethanol via the generation of α-hydroxyethyl radical when L-arginine is present

Nitric oxide activation by distal redox modulation in tetranuclear iron nitrosyl complexes.

Science.gov (United States)

de Ruiter, Graham; Thompson, Niklas B; Lionetti, Davide; Agapie, Theodor

2015-11-11

A series of tetranuclear iron complexes displaying a site-differentiated metal center was synthesized. Three of the metal centers are coordinated to our previously reported ligand, based on a 1,3,5-triarylbenzene motif with nitrogen and oxygen donors. The fourth (apical) iron center is coordinatively unsaturated and appended to the trinuclear core through three bridging pyrazolates and an interstitial μ4-oxide moiety. Electrochemical studies of complex [LFe3(PhPz)3OFe][OTf]2 revealed three reversible redox events assigned to the Fe(II)4/Fe(II)3Fe(III) (-1.733 V), Fe(II)3Fe(III)/Fe(II)2Fe(III)2 (-0.727 V), and Fe(II)2Fe(III)2/Fe(II)Fe(III)3 (0.018 V) redox couples. Combined Mössbauer and crystallographic studies indicate that the change in oxidation state is exclusively localized at the triiron core, without changing the oxidation state of the apical metal center. This phenomenon is assigned to differences in the coordination environment of the two metal sites and provides a strategy for storing electron and hole equivalents without affecting the oxidation state of the coordinatively unsaturated metal. The presence of a ligand-binding site allowed the effect of redox modulation on nitric oxide activation by an Fe(II) metal center to be studied. Treatment of the clusters with nitric oxide resulted in binding of NO to the apical iron center, generating a {FeNO}(7) moiety. As with the NO-free precursors, the three reversible redox events are localized at the iron centers distal from the NO ligand. Altering the redox state of the triiron core resulted in significant change in the NO stretching frequency, by as much as 100 cm(-1). The increased activation of NO is attributed to structural changes within the clusters, in particular, those related to the interaction of the metal centers with the interstitial atom. The differences in NO activation were further shown to lead to differential reactivity, with NO disproportionation and N2O formation performed by the more

Intracellular conversion of environmental nitrate and nitrite to nitric oxide with resulting developmental toxicity to the crustacean Daphnia magna.

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Bethany R Hannas

2010-08-01

Full Text Available Nitrate and nitrite (jointly referred to herein as NO(x are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NO(x undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes.These experiments were performed with insect cells (Drosophila S2 and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO(3(- and nitrite (NO(2(- to nitric oxide using amperometric real-time nitric oxide detection. Both NO(3(- and NO(2(- were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO(2(- to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control and to concentrations of NO(3(- and NO(2(-. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers.Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide.

Nitric oxide enhances osmoregulation of tobacco ( Nicotiana ...

African Journals Online (AJOL)

This study was carried out to investigate the effect of the intracellular signaling molecule nitric oxide (NO) on osmoregulation of tobacco cells under osmotic stress caused by phenylethanoid glycosides 6000 (PEG 6000). The results show that the PEG stress induced a specific pattern of endogenous NO production with two ...

Inhibition of Inducible Nitric Oxide Synthase, Cycleooxygenase-2 ...

African Journals Online (AJOL)

HP

Won Chung, Jin Uk Oh, Sehyung Lee and Sung-Jin Kim* ... was determined by Western blot analysis for iNOS and COX-2 expression in LPS-stimulated RAW ..... Nitric oxide-scavenging and antioxidant effects ofUraria crinite root. Food.

Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease

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Noboru Toda

2016-08-01

Full Text Available Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic nerves and nitric oxide (NO liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS/neuronal NOS (nNOS inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD. Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD.

Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

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Bruno P. Carreira

2015-01-01

Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.

Lack of endothelial nitric oxide synthase aggravates murine accelerated anti-glomerular basement membrane glomerulonephritis

NARCIS (Netherlands)

Heeringa, P; van Goor, H; Itoh-Lindstrom, Y; Maeda, N; Falk, RJ; Assmann, KJM; Kallenberg, CGM; Jennette, JC

Nitric oxide (NO) radicals generated by endothelial nitric oxide synthase (eNOS) are involved in the regulation of vascular tone. In addition, NO radicals derived from eNOS inhibit platelet aggregation and leukocyte adhesion to the endothelium and, thus, may have anti-inflammatory effects. To study

Trigeminocardiac reflex by mandibular extension on rat pial microcirculation: role of nitric oxide.

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Dominga Lapi

Full Text Available In the present study we have extended our previous findings about the effects of 10 minutes of passive mandibular extension in anesthetized Wistar rats. By prolonging the observation time to 3 hours, we showed that 10 minutes mandibular extension caused a significant reduction of the mean arterial blood pressure and heart rate respect to baseline values, which persisted up to 160 minutes after mandibular extension. These effects were accompanied by a characteristic biphasic response of pial arterioles: during mandibular extension, pial arterioles constricted and after mandibular extension dilated for the whole observation period. Interestingly, the administration of the opioid receptor antagonist naloxone abolished the vasoconstriction observed during mandibular extension, while the administration of Nω-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, abolished the vasodilation observed after mandibular extension. Either drug did not affect the reduction of mean arterial blood pressure and heart rate induced by mandibular extension. By qRT-PCR, we also showed that neuronal nitric oxide synthase gene expression was significantly increased compared with baseline conditions during and after mandibular extension and endothelial nitric oxide synthase gene expression markedly increased at 2 hours after mandibular extension. Finally, western blotting detected a significant increase in neuronal and endothelial nitric oxide synthase protein expression. In conclusion mandibular extension caused complex effects on pial microcirculation involving opioid receptor activation and nitric oxide release by both neurons and endothelial vascular cells at different times.

Nitric oxide as a potential biomarker in inflammatory bowel disease

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Nesina Avdagić

2013-02-01

Full Text Available The aim of this study was to investigate changes in serum nitric oxide (NO concentration in inflammatory bowel diseases (IBD patients and its use as potential biomarker in differential diagnosis of ulcerative colitis (UC and Crohn's disease (CD and in disease activity assessment. In 60 patients of both genders - 30 with ulcerative colitis and 30 with Crohn's disease - and 30 controls serum nitric oxide concentration was determined by measuring nitrite concentration, a stable metabolic product of NO with oxygen. Conversion of nitrates (NO3- to nitrites (NO2- was done with elementary zinc. The nitrite concentration was determined by classic colorimetrical Griess reaction. Median serum NO concentration was statistically different (p=0,0005 between UC patients (15.25 µmol/L; 13.47 - 19.88 µmol/L, CD patients (14.54 µmol/L; 13.03 -16.32 µmol/L and healthy controls (13.29 µmol/L; 12.40 - 13.92 µmol/L. When active UC and CD patients were compared with inactive UC and CD patients respectively a significant difference in serum NO level was found (p=0.0005. With a cut-off level of 17.39 µmol/L NO had a sensitivity of 100% and a specificity of 100% in discriminating between active and inactive UC patients. With cut-off value of 14.01 µmol/L serum NO level had a sensitivity of 88% and a specificity of 69% in distinguishing between patients with active CD and inactive CD. Serum NO concentration is a minimally invasive and rapid tool for discriminating between active and inactive IBD patients and could be used as useful biomarker in monitoring of disease activity in IBD patients.

The Effect of Polyunsaturated Aldehydes on Skeletonema marinoi (Bacillariophyceae: The Involvement of Reactive Oxygen Species and Nitric Oxide

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Alessandra A. Gallina

2014-07-01

Full Text Available Nitric oxide (NO and reactive oxygen species (ROS production was investigated in the marine diatom, Skeletonema marinoi (SM, exposed to 2E,4E/Z-decadienal (DECA, 2E,4E/Z-octadienal (OCTA, 2E,4E/Z-heptadienal (HEPTA and a mix of these last two (MIX. When exposed to polyunsaturated aldehydes (PUA, a decrease of NO was observed, proportional to the PUA concentration (85% of the initial level after 180 min with 66 µM DECA. Only OCTA, HEPTA and MIX induced a parallel increase of ROS, the highest (2.9-times the control with OCTA concentrations twice the EC50 for growth at 24 h (20 μM. The synthesis of carotenoids belonging to the xanthophyll cycle (XC was enhanced during exposure, suggesting their antioxidant activity. Our data provide evidence that specific pathways exist as a reaction to PUA and that they depend upon the PUA used and/or the diatom species. In fact, Phaeodactylum tricornutum (PT produces NO in response to DECA, but not to OCTA. We advance the hypothesis that SM perceives OCTA and HEPTA as intra-population infochemicals (as it produces PUA, while PT (non-PUA producing species perceives them as allelochemicals. The ability to produce and to use PUA as infochemicals may underlie ecological traits of different diatom species and modulate ecological success in natural communities.

Mechanism of vasoconstriction induced by chronic inhibition of nitric oxide in rats.

Science.gov (United States)

Bank, N; Aynedjian, H S; Khan, G A

1994-09-01

Either acute or chronic inhibition of nitric oxide synthesis by L-arginine analogues results in increases in mean arterial pressure and reductions in renal blood flow. The role of endogenous vasoconstrictors in mediating these effects is not entirely clear. In the present study, nitric oxide was inhibited in male Sprague-Dawley rats by oral administration of nitro-L-arginine for 3 weeks. At the end of this time, mean arterial pressure was 30 to 40 mm Hg higher than in normal controls, renal blood flow and glomerular filtration rate were 25% to 30% lower, and renal vascular resistance was markedly increased. Intravenous infusion of receptor antagonists for angiotensin II, thromboxane, epinephrine, and endothelin-1 had no significant effect on the hypertension. Inhibition of prostaglandin synthesis and furosemide-induced diuresis in the presence of angiotensin blockade also had no effect on blood pressure. Renal vascular resistance was also unaffected by these interventions, except that saralasin did reduce renal resistance in both control and nitric oxide-inhibited groups. However, the absolute level of renal vascular resistance remained higher in the latter group. Calcium channel blockade partially corrected blood pressure and renal resistance, but the levels remained significantly higher than in control animals. The findings are consistent with the view that the increase in vascular smooth muscle tone caused by inhibition of nitric oxide synthesis cannot be accounted for by overexpression of common endogenous vasoconstrictors. Rather, the generalized increase in vascular smooth muscle tone appears to be due to a direct effect of reduced nitric oxide availability, which may lead to an increase in intracellular calcium concentration or sensitivity.

Serum ferritin, serum nitric oxide, and cognitive function in pediatric thalassemia major

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Septiana Nur Qurbani

2017-06-01

Full Text Available Background Hemolysis and repeated blood transfusions in children with thalassemia major cause iron overload in various organs, including the brain, and may lead to neurodegeneration. Hemolysis also causes decreased levels of nitric oxide, which serves as a volume transmitter and slow dynamic modulation, leading to cognitive impairment. Objective To assess for correlations between serum ferritin as well as nitric oxide levels and cognitive function in children with thalassemia major.  Methods This analytical study with cross-sectional design on 40 hemosiderotic thalassemia major patients aged 6−14 years, was done at the Thalassemia Clinic in Dr. Hasan Sadikin Hospital, Bandung, West Java, from May to June 2015. Serum ferritin measurements were performed by an electrochemiluminescence immunoassay; serum nitric oxide was assayed by a colorimetric procedure based on Griess reaction; and cognitive function was assessed by the Wechsler Intelligence Scale for Children test. Statistical analysis was done using Spearman’s Rank correlation, with a significance value of 0.05. Results Abnormal values in verbal, performance, and full scale IQ were found in 35%, 57.5% and 57.5%, respectively. Serum nitric oxide level was significantly correlated with performance IQ (P=0.022, but not with verbal IQ (P=0.359 or full scale IQ (P=0.164. There were also no significant correlations between serum ferritin level and full scale, verbal, or performance IQ (P=0.377, 0.460, and 0.822, respectively. Conclusion Lower serum nitric oxide level is significantly correlated to lower cognitive function, specifically in the performance IQ category. However, serum ferritin level has no clear correlation with cognitive function.

The air we breathe: three vital respiratory gases and the red blood cell: oxygen, nitric oxide, and carbon dioxide.

Science.gov (United States)

Dzik, Walter H

2011-04-01

Three vital respiratory gases-oxygen (O(2)), nitric oxide (NO), and carbon dioxide (CO(2))-intersect at the level of the human red blood cell (RBC). In addition to hemoglobin (Hb)'s central role in O(2) transport, interaction of Hb with the Band 3 metabolon balances RBC energy flow. 2,3-Diphosphoglycerate enhances O(2) transport across the placenta and plays an important role in regulating RBC plasticity. NO is a key mediator of hypoxic vasodilation, but the precise role of RBC Hb remains controversial. In addition to established theories that depend on RBC uptake, delivery, and discharge of NO or its metabolites, an alternative hypothesis based on RBC permeability is suggested. NO depletion by free Hb may account for several clinical features seen during intravascular hemolysis or during deliberate infusion of Hb solutions used as RBC substitutes. CO(2) released by tissues triggers oxygen release through a series of well-coordinated reactions centered on the Band 3 metabolon. While RBC carbonic anhydrase and the Band 3 anion exchanger are central to this process, there is surprisingly little research on the kinetics of CO(2) clearance by transfusion. The three RBC gases are directly related to the three principal gases of Earth's atmosphere. Human fossil fuel consumption dumps 90 million metric tons of carbon into the atmosphere annually. Increasing CO(2) levels are linked to global warming, melting Arctic ice, rising sea levels, and climate instability. Just as individual cells depend on balance of the three vital gases, so too will their balance determine survival of life on Earth. © 2011 American Association of Blood Banks.

Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons.

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Lopez, Jose R; Uryash, A; Kolster, J; Estève, E; Zhang, R; Adams, J A

2018-03-26

We have previously shown that inadequate dystrophin in cortical neurons in mdx mice is associated with age-dependent dyshomeostasis of resting intracellular Ca 2+ ([Ca 2+ ] i ) and Na + ([Na + ] i ), elevated reactive oxygen species (ROS) production, increase in neuronal damage and cognitive deficit. In this study, we assessed the potential therapeutic properties of the whole body periodic acceleration (pGz) to ameliorate the pathology observed in cortical neurons from the mdx mouse. pGz adds small pulses to the circulation, thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of nitric oxide (NO). We found [Ca 2+ ] i and [Na + ] i overload along with reactive oxygen species (ROS) overproduction in mdx neurons and cognitive dysfunction. mdx neurons showed increased activity of superoxide dismutase, glutathione peroxidase, malondialdehyde, and calpain as well as decreased cell viability. mdx neurons were more susceptible to hypoxia-reoxygenation injury than WT. pGz ameliorated the [Ca 2+ ] i , and [Na + ] i elevation and ROS overproduction and further increased the activities of superoxide dismutase, glutathione peroxidase and reduced the malondialdehyde and calpains. pGz diminished cell damage and elevated [Ca 2+ ] i during hypoxia-reoxygenation and improved cognitive function in mdx mice. Moreover, pGz upregulated the expression of utrophin, dystroglycan-β and CAPON, constitutive nitric oxide synthases, prosaposin, brain-derived neurotrophic, and glial cell line-derived neurotrophic factors. The present study demonstrated that pGz is an effective therapeutic approach to improve mdx neurons function, including cognitive functions.

Standardisation and application of the single-breath determination of nitric oxide uptake in the lung.

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Zavorsky, Gerald S; Hsia, Connie C W; Hughes, J Michael B; Borland, Colin D R; Guénard, Hervé; van der Lee, Ivo; Steenbruggen, Irene; Naeije, Robert; Cao, Jiguo; Dinh-Xuan, Anh Tuan

2017-02-01

Diffusing capacity of the lung for nitric oxide ( D LNO ), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breath D LNO This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar "collection" or continuously sampled via rapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4-6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40-60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension ( P AO 2 ) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min -1 ·mmHg -1 ·mL -1 of blood; 6) the equation for 1/θCO should be (0.0062· P AO 2 +1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holding P AO 2 and adjusted to an average haemoglobin concentration (male 14.6 g·dL -1 , female 13.4 g·dL -1 ); 7) a membrane diffusing capacity ratio ( D MNO / D MCO ) should be 1.97, based on tissue diffusivity. Copyright ©ERS 2017.

Critical evaluation of pressurized microwave-assisted digestion efficiency using nitric acid oxidizing systems (M7)

International Nuclear Information System (INIS)

Matusiewicz, H.

2002-01-01

Full text: The possibilities of enhancement of a medium-pressure microwave-assisted digestion system for sample preparation in trace element analysis of biological material was investigated. Based on optimal digestion conditions for oxidizing systems with nitric acid, different digestion procedures were examined to minimize residual carbon. The substitution of nitric acid and the addition of hydrogen peroxide and ozone to nitric acid was evaluated. The residual carbon content of the digestate was determined coulometrically. Addition of hydrogen peroxide during organic oxidation reactions does not lower the resolved carbon in the solution. Ozone was tested as an additional, potentially non-contaminating, digestion/oxidation system to the nitric acid used in the sample preparation method. (author)

Involvement of beta 3-adrenoceptor in altered beta-adrenergic response in senescent heart: role of nitric oxide synthase 1-derived nitric oxide.

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Birenbaum, Aurélie; Tesse, Angela; Loyer, Xavier; Michelet, Pierre; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno; Amour, Julien

2008-12-01

In senescent heart, beta-adrenergic response is altered in parallel with beta1- and beta2-adrenoceptor down-regulation. A negative inotropic effect of beta3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that beta3-adrenoceptor plays a role in beta-adrenergic dysfunction in senescent heart. beta-Adrenergic responses were investigated in vivo (echocardiography-dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and beta-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline +/- SD. An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 +/- 23 vs. 162 +/- 16%; P < 0.05) and in vitro (127 +/- 10 vs. 179 +/- 15%; P < 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor N-nitro-L-arginine methylester (L-NAME; 183 +/- 19%), the selective NOS1 inhibitor vinyl-L-N-5(1-imino-3-butenyl)-L-ornithine (L-VNIO; 172 +/- 13%), or the selective NOS2 inhibitor 1400W (183 +/- 19%). In the senescent group, in parallel with beta3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by L-NAME (151 +/- 8%; P < 0.05) and L-VNIO (149 +/- 7%; P < 0.05) but not by 1400W (132 +/- 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific beta3-adrenoceptor agonist BRL 37344 (167 +/- 10 vs. 142 +/- 10%; P < 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. In senescent cardiomyopathy, beta3-adrenoceptor overexpression plays an important role in the

Fluorescence-based detection of nitric oxide in aqueous and methanol media using a copper(II) complex.

Science.gov (United States)

Mondal, Biplab; Kumar, Pankaj; Ghosh, Pokhraj; Kalita, Apurba

2011-03-14

The quenched fluorescent intensity of a copper(II) complex, 1, of a fluorescent ligand, in degassed methanol or aqueous (buffered at pH 7.2) solution, was found to reappear on exposure to nitric oxide. Thus, it can function as a fluorescence based nitric oxide sensor. It has been found that the present complex can be used to sense nanomolar quantities of nitric oxide in both methanol and pH 7.2 buffered-water medium.

Regulation and control of nitric oxide (NO) in macrophages

DEFF Research Database (Denmark)

Kovacevic, Zaklina; Sahni, Sumit; Lok, K.H.

2017-01-01

We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transp......We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores...... be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MØs, to tumor cell targets....

The effect of nitric oxide releasing cream on healing pressure ulcers

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Vahid Saidkhani

2016-01-01

Full Text Available Background: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. Materials and Methods: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29 and control (placebo cream; n = 29. In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH. At the outset of the study (before using the cream, the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Results: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing between the two groups was statistically significant (P = 0.04. Conclusions: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future.

The effect of nitric oxide releasing cream on healing pressure ulcers

Science.gov (United States)

Saidkhani, Vahid; Asadizaker, Marziyeh; Khodayar, Mohammad Javad; Latifi, Sayed Mahmoud

2016-01-01

Background: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO) has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. Materials and Methods: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29) and control (placebo cream; n = 29). In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH). At the outset of the study (before using the cream), the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Results: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing) between the two groups was statistically significant (P = 0.04). Conclusions: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future. PMID:27186212

Up-regulation of cytosolic phospholipase A2α expression by N,N-diethyldithiocarbamate in PC12 cells; involvement of reactive oxygen species and nitric oxide

International Nuclear Information System (INIS)

Akiyama, Nobuteru; Nabemoto, Maiko; Hatori, Yoshio; Nakamura, Hiroyuki; Hirabayashi, Tetsuya; Fujino, Hiromichi; Saito, Takeshi; Murayama, Toshihiko

2006-01-01

Disulfiram (an alcohol-aversive drug) and related compounds are known to provoke several side effects involving behavioral and neurological complications. N,N-diethyldithiocarbamate (DDC) is considered as one of the main toxic species of disulfiram and acts as an inhibitor of superoxide dismutase. Since arachidonic acid (AA) formation is regulated by reactive oxygen species (ROS) and related to toxicity in neuronal cells, we investigated the effects of DDC on AA release and expression of the α type of cytosolic phospholipase A 2 (cPLA 2 α) in PC12 cells. Treatment with 80-120 μM DDC that causes a moderate increase in ROS levels without cell toxicity stimulated cPLA 2 α mRNA and its protein expression. The expression was mediated by extracellular-signal-regulated kinase (ERK1/2), one of the mitogen-activated protein kinases. Treatment with N G nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase, 1 mM) and oxy-hemoglobin (a scavenger of nitric oxide, 2 mg/mL) abolished the DDC-induced responses (ERK1/2 phosphorylation and cPLA 2 α expression). We also showed DDC-induced up-regulation of the mRNA expression of lipocortin 1, an inhibitor of PLA 2 . Furthermore, DDC treatment of the cells enhanced Ca 2+ -ionophore-induced AA release in 30 min, although the effect was limited. Changes in AA metabolism in DDC-treated cells may have a potential role in mediating neurotoxic actions of disulfiram. In this study, we show the first to demonstrate the up-regulation of cPLA 2 α expression by DDC treatment in neuronal cells

Dalton's disputed nitric oxide experiments and the origins of his atomic theory.

Science.gov (United States)

Usselman, Melvyn C; Leaist, Derek G; Watson, Katherine D

2008-01-11

In 1808 John Dalton published his first general account of chemical atomic theory, a cornerstone of modern chemistry. The theory originated in his earlier studies of the properties of atmospheric gases. In 1803 Dalton discovered that oxygen combined with either one or two volumes of nitric oxide in closed vessels over water and this pioneering observation of integral multiple proportions provided important experimental evidence for his incipient atomic ideas. Previous attempts to reproduce Dalton's experiments have been unsuccessful and some commentators have concluded the results were fraudulent. We report a successful reconstruction of Dalton's experiments and provide an analysis exonerating him of any scientific misconduct. But we conclude that Dalton, already thinking atomistically, adjusted experimental conditions to obtain the integral combining proportions.

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

Science.gov (United States)

Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

2016-01-01

Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

Directory of Open Access Journals (Sweden)

Elena Lima-Cabello

2016-01-01

Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases

DEFF Research Database (Denmark)

Reimers, J I; Bjerre, U; Mandrup-Poulsen, T

1994-01-01

Substantial in vitro evidence suggests that nitric oxide may be a major mediator of interleukin 1 (IL-1) induced pancreatic beta-cell inhibition and destruction in the initial events leading to insulin-dependent diabetes mellitus. Using NG-nitro-L-arginine methyl ester, an inhibitor of both...

Low concentrations of salicylic acid delay methyl jasmonate-induced leaf senescence by up-regulating nitric oxide synthase activity.

Science.gov (United States)

Ji, Yingbin; Liu, Jian; Xing, Da

2016-09-01

In plants, extensive efforts have been devoted to understanding the crosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling in pathogen defenses, but this crosstalk has scarcely been addressed during senescence. In this study, the effect of SA application on methyl jasmonate (MeJA)-induced leaf senescence was assessed. We found that low concentrations of SA (1-50 μM) played a delayed role against the senescence promoted by MeJA. Furthermore, low concentrations of SA enhanced plant antioxidant defenses and restricted reactive oxygen species (ROS) accumulation in MeJA-treated leaves. When applied simultaneously with MeJA, low concentrations of SA triggered a nitric oxide (NO) burst, and the elevated NO levels were linked to the nitric oxide associated 1 (NOA1)-dependent pathway via nitric oxide synthase (NOS) activity. The ability of SA to up-regulate plant antioxidant defenses, reduce ROS accumulation, and suppress leaf senescence was lost in NO-deficient Atnoa1 plants. In a converse manner, exogenous addition of NO donors increased the plant antioxidant capacity and lowered the ROS levels in MeJA-treated leaves. Taken together, the results indicate that SA at low concentrations counteracts MeJA-induced leaf senescence through NOA1-dependent NO signaling and strengthening of the antioxidant defense. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

On EPR detection of nitric oxide in vivo

NARCIS (Netherlands)

van Faassen, E.E.H.

2008-01-01

Nitric oxide (NO ) is a peculiar radical: Ground state is not paramagnetic (g = 0 since orbital and spin magnetic moments cancel); low reactivity with other molecules except superoxide (O2 ); thermodynamically unstable; dimerizes to N2O2; difficult to detect in-vivo.

Arginine, citrulline and nitric oxide metabolism in sepsis

Science.gov (United States)

Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

The effects of nitric oxide cooling and the photodissociation of molecular oxygen on the thermosphere/ionosphere system over the Argentine Islands

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G. D. Wells

1997-03-01

Full Text Available In the past the global, fully coupled, time-dependent mathematical model of the Earth's thermosphere/ionosphere/plasmasphere (CTIP has been unable to reproduce accurately observed values of the maximum plasma frequency, foF2, at extreme geophysical locations such as the Argentine Islands during the summer solstice where the ionosphere remains in sunlight throughout the day. This is probably because the seasonal dependence of thermospheric cooling by 5.3 µm nitric oxide has been neglected and the photodissociation of O2 and heating rate calculations have been over-simplified. Now we have included an up-to-date calculation of the solar EUV and UV thermospheric heating rate, coupled with a new calculation of a diurnally varying O2 photodissociation rate, in the model. Seasonally dependent 5.3 µm nitric oxide cooling is also included. With these important improvements, it is found that model values of foF2 are in substantially better agreement with observation. The height of the F2-peak is reduced throughout the day, but remains within acceptable limits of values derived from observation, except at around 0600 h LT. We also carry out two studies of the sensitivity of the upper atmosphere to changes in the magnitude of nitric oxide cooling and photodissociation rates. We find that hmF2 increases with increased heating, whilst foF2 falls. The converse is true for an increase in the cooling rate. Similarly increasing the photodissociation rate increases both hmF2 and foF2. These changes are explained in terms of changes in the neutral temperature, composition and neutral wind.

Arginine affects appetite via nitric oxide in ducks.

Science.gov (United States)

Wang, C; Hou, S S; Huang, W; Xu, T S; Rong, G H; Xie, M

2014-08-01

The objective of the study was to investigate the mechanism by which arginine regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d-old male Pekin ducks were randomly allotted to 3 dietary treatments with 6 replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P ducks were allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl (L-NAME) for 3 d, respectively. Feed intake (P study implied that arginine modifies feeding behavior possibly through controlling endogenous synthesis of nitric oxide in Pekin ducks. © Poultry Science Association Inc.

Nitric Oxide - Its Importance in Swallowing, Inflammatory Bowel Disease and Cirrhotic Cardiomyopathy

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ABR Thomson

2001-01-01

Full Text Available Nitric oxide is a neurotransmitter found in the central and peripheral nervous systems. Nitric oxide synthase (NOS is localized in the central nervous system, including the nucleus of the solitary tract, nucleus ambiguus and dorsal motor nucleus of the vagus. These are regions that are implicated in the central control of swallowing and esophageal motility. In rats and rabbits, NOS has been shown to be present in the nucleus subcentralis of the nucleus of the solitary tract, and is thought to be responsible for the central programming of the striated muscle component of esophageal peristalsis. Beyak and co-workers from the University of Toronto, Toronto, Ontario provided evidence that the L-arginine-nitric oxide pathway is implicated in the central control of swallowing and esophageal motility. They studied oropharyngeal swallowing as well as esophageal peristalsis, and determined the functional role of brain stem nitric oxide by examining the effects of blockade of central nervous system NOS on swallowing, and on primary and secondary peristalsis. Administering NOS inhibitors intravenously or intracerebroventricularly into the fourth ventricle produced a number of oropharyngeal swallows and induced primary peristalsis in the smooth muscle portion of the esophageal body. NOS reduced the number of oropharyngeal swallows and the incidence of primary peristalsis in both smooth and striated muscle, and reduced the amplitude of peristalsis and smooth muscle contraction. This suggests that nitric oxide is a functional neurotransmitter in the central pattern generator responsible for swallowing and the central control of esophageal peristalsis. Peripherally administered NOS inhibitor can access structures within the blood-brain barrier to affect neuronal activity and physiological function. The central pattern generated for swallowing and esophageal peristalsis is suggested to be a serial network of linked neurons within the nucleus of the solitary

Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania.

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Chan, Marion Man-Ying; Adapala, Naga Suresh; Fong, Dunne

2005-04-01

Upon Leishmania infection, macrophages are activated to produce nitrogen and oxygen radicals simultaneously. It is well established that the infected host cells rely on nitric oxide (NO) as the major weapon against the intracellular parasite. In India where leishmaniasis is endemic, the spice turmeric is used prolifically in food and for insect bites. Curcumin, the active principle of turmeric, is a scavenger of NO. This report shows that curcumin protects promastigotes and amastigotes of the visceral species, Leishmania donovani, and promastigotes of the cutaneous species, L. major, against the actions of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and DETANONOate, which release NO, 3-morpholino-sydnonimine hydrochloride (SIN-1), which releases NO and superoxide, and peroxynitrite, which is formed from the reaction of NO with superoxide. Thus, curcumin, as an antioxidant, is capable of blocking the action of both NO and NO congeners on the Leishmania parasite.

DMPD: Regulation of nitric oxide synthesis and apoptosis by arginase and argininerecycling. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17513437 Regulation of nitric oxide synthesis and apoptosis by arginase and arginin...tion of nitric oxide synthesis and apoptosis by arginase and argininerecycling. A...erecycling. Mori M. J Nutr. 2007 Jun;137(6 Suppl 2):1616S-1620S. (.png) (.svg) (.html) (.csml) Show Regulation of nitric oxide synthe...sis and apoptosis by arginase and argininerecycling. PubmedID 17513437 Title Regula

Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

Science.gov (United States)

Sorokin, Andrey

2016-01-01

The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.

Science.gov (United States)

Stamler, J S; Jaraki, O; Osborne, J; Simon, D I; Keaney, J; Vita, J; Singel, D; Valeri, C R; Loscalzo, J

1992-01-01

We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be

Nitric oxide and non-quantal acetylcholine release

Czech Academy of Sciences Publication Activity Database

Vyskočil, František

2003-01-01

Roč. 7, č. 3 (2003), s. 241-243 ISSN 1211-7579. [Celostátní konference biologické psychiatrie /11./. Luhačovice, 11.06.2003-14.06.2003] R&D Projects: GA ČR GA305/02/1333 Institutional research plan: CEZ:AV0Z5011922; CEZ:MSM 113100003 Keywords : nitric oxide Subject RIV: ED - Physiology

Highly sensitive voltammetric biosensor for nitric oxide based on its high affinity with hemoglobin

International Nuclear Information System (INIS)

Fan Chunhai; Liu Xinjian; Pang Jiantao; Li Genxi; Scheer, Hugo

2004-01-01

Although heme protein-based, amperometric nitric oxide (NO) biosensors have been well documented in previous studies, most have been conducted in anaerobic conditions. Herein we report a novel hemoglobin-based NO biosensor that is not only very sensitive but also usable in air. The heme protein was entrapped in a sodium montmorillonite film, which was immobilized at a pyrolytic graphite electrode surface. Film-entrapped hemoglobin can directly exchange electrons with the electrode, and this process has proven to favor the catalytic reduction of oxygen. In addition, NO induced a cathodic potential shift of the catalytic reduction peak of oxygen. This potential shift was proportional to the logarithm of NO concentration ranging from 4.0 x 10 -11 to 5.0 x 10 -6 mol/L. The detection limit has been estimated to be 20 pM, approximately four orders lower than previously reported amperometric detectors

Role of heat shock protein 90 and endothelial nitric oxide synthase during early anesthetic and ischemic preconditioning.

Science.gov (United States)

Amour, Julien; Brzezinska, Anna K; Weihrauch, Dorothee; Billstrom, Amie R; Zielonka, Jacek; Krolikowski, John G; Bienengraeber, Martin W; Warltier, David C; Pratt, Philip F; Kersten, Judy R

2009-02-01

Nitric oxide is known to be essential for early anesthetic preconditioning (APC) and ischemic preconditioning (IPC) of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, the authors tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning within 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pretreatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or N-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or N-nitro-L-arginine methyl ester. Interactions between Hsp90 and eNOS, and eNOS activation, were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. APC and IPC decreased infarct size (by 50% and 59%, respectively), and this action was abolished by Hsp90 inhibitors. N-nitro-L-arginine methyl ester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes, and eNOS was below the level of detection. The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signaling during APC.

Role of nitric oxide in pheromone-mediated intraspecific communication in mice.

Science.gov (United States)

Agustín-Pavón, Carmen; Martínez-Ricós, Joana; Martínez-García, Fernando; Lanuza, Enrique

2009-12-07

Nitric oxide is known to take part in the control of sexual and agonistic behaviours. This is usually attributed to its role in neural transmission in the hypothalamus and other structures of the limbic system. However, socio-sexual behaviours in rodents are mainly directed by chemical signals detected by the vomeronasal system, and nitric oxide is abundant in key structures along the vomeronasal pathway. Thus, here we check whether pharmacological treatments interfering with nitrergic transmission could affect socio-sexual behaviour by impairing the processing of chemical signals. Treatment with an inhibitor of nitric oxide synthesis (Nomega-Nitro-l-arginine methyl ester hydrochloride, L-NAME, 100mg/kg) blocks the innate preference displayed by female mice for sexual pheromones contained in male-soiled bedding, with a lower dose of the drug (50mg/kg) having no effect. Animals treated with the high dose of L-NAME show no reduction of olfactory discrimination of male urine in a habituation-dishabituation test, thus suggesting that the effect of the drug on the preference for male pheromones is not due to an inability to detect male urine. Alternatively, it may result from an alteration in processing the reinforcing value of pheromones as sexual signals. These results add a new piece of evidence to our understanding of the neurochemistry of intraspecific chemical communication in rodents, and suggest that the role of nitric oxide in socio-sexual behaviours should be re-evaluated taking into account the involvement of this neuromodulator in the processing of chemical signals.

Nitric oxide and neopterin in bipolar affective disorder

NARCIS (Netherlands)

Hoekstra, R.; Fekkes, D.; Pepplinkhuizen, L.; Loonen, A.J.M.; Tuinier, S.; Verhoeven, W.M.A.

2006-01-01

Background: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. Methods: In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and

Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial VO2 during exercise

DEFF Research Database (Denmark)

Boushel, Robert C; Fuentes, Teresa; Hellsten, Ylva

2012-01-01

Nitric oxide (NO) and prostaglandins (PG) together play a role in regulation blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome c oxidase. Indomethacin both uncouples and inhibits the electron transport chain in a concentration......-dependent manner, and thus inhibition of NO and PG may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG blockade (L-NMMA and indomethacin respectively) on mitochondrial respiration in human muscle following knee...... extension (KE) exercise. Mitochondrial respiration was measured ex-vivo by high resolution respirometry in saponin-permeabilized fibers following 6 min KE in control (CON, n=8), arterial infusion of LNMMA (n=4) and Indo (n=4) followed by combined inhibition of NO and PG (L-NMMA + Indo, n=8). ADP...

NITRIC OXIDE AND ENDOTHELIN-1 IN CHILDREN WITH DIGESTIVE DISORDERS

Directory of Open Access Journals (Sweden)

I. V. Panova

2012-01-01

Full Text Available The important part in the group of biological compounds, participating in the regulation of the functions of the gastro-intestinal tract, is assigned to endothelial factors because of their impact on the majority of physiological and pathophysiological processes of the digestive system. The article provides information about physiological role of nitric oxide and endothelin-1 and presents a review of scientific data on the participation of nitric oxide and endothelin-1 in the pathogenesis of many digestive system diseases, emphasizing chronic inflammatory disorders of the upper gastrointestinal tract. The authors accentuate the importance of endothelium endocrine function research in children with esophagogastroduodenal disorders at the beginning of puberty, which is the critical period of ontogenesis.

Stimulation of nitric oxide synthesis by the aqueous extract of Panax ginseng root in RAW 264.7 cells.

Science.gov (United States)

Friedl, R; Moeslinger, T; Kopp, B; Spieckermann, P G

2001-12-01

1. In this study, we investigated the effect of Panax ginseng root aqueous extracts upon inducible nitric oxide synthesis in RAW 264.7 cells. Panax ginseng root extract has been used in the Asian world for centuries as a traditional herb to enhance physical strength and resistance and is becoming more and more popular in Europe and North America. 2. Incubation of murine macrophages (RAW 264.7 cells) with increasing amounts of aqueous extracts of Panax ginseng (0.05 - 0.8 microg microl(-1)) showed a dose dependent stimulation of inducible nitric oxide synthesis. 3. Polysaccharides isolated from Panax ginseng showed strong stimulation of inducible nitric oxide synthesis, whereas a triterpene-enriched fraction from an aqueous extract of Panax ginseng did not show any stimulation. 4. Inducible nitric oxide synthase protein expression was enhanced in a dose dependent manner as revealed by immunoblotting when cells were incubated with increasing amounts of Panax ginseng extract. This was associated with an incline in inducible nitric oxide synthase mRNA-levels as determined by semiquantitative polymerase chain reaction and electromobility shift assay studies indicated enhanced nuclear factor-kappaB DNA binding activity. 5. As nitric oxide plays an important role in immune function, Panax ginseng treatment could modulate several aspects of host defense mechanisms due to stimulation of the inducible nitric oxide synthase.

Induction of chilling tolerance in wheat during germination by pre-soaking seed with nitric oxide and gibberellin

DEFF Research Database (Denmark)

Li, Xiangnan; Jiang, Haidong; Liu, Fulai

2013-01-01

Chilling depresses seed germination and seedling establishment, and is one major constraint to grain yield formation in late sown winter wheat. Seeds of winter wheat (Triticum aestivum L.) were separately pre-soaked with sodium nitroprusside (SNP, as nitric oxide donor) and Gibberellic acid (GA3...... by exogenous NO and GA3 as a result of improved seed germination and maintenance of better reactive oxygen species homeostasis in seedling growing under chilling temperatures. It is indicated that exogenous NO was more effective than GA3 in alleviating chilling stress during seed germination and seedling...

Treatment Of Sunitinib-Induced Hypertension In Solid Tumors By Nitric Oxid Donors

Directory of Open Access Journals (Sweden)

Luís A. Leon

2015-08-01

Hypertension (HT is one of the most common adverse effects of angiogenesis inhibitors. Hypertension observed in clinical trials appears to correlate with the potency of VEGF kinase inhibitor against VEGFR-2: agents with higher potency are associated with a higher incidence of hypertension. Although the exact mechanism by TKIs induce hypertension has not yet been completely clarified, two key hypotheses have been postulated. First, some studies have pointed to a VEGF inhibitors-induced decrease in nitric oxide synthase (NOS and nitric oxide (NO production, that can result in vasoconstriction and increased blood pressure. VEGF, mediated by PI3K/Akt and MAPK pathway, upregulates the endothelial nitric oxide synthase enzyme leading to up-regulation of NO production. So inhibition of signaling through the VEGF pathway would lead to a decrease in NO production, resulting in an increase in vascular resistance and blood pressure. Secondly a decrease in the number of microvascular endothelial cells and subsequent depletion of normal microvessel density (rarefaction occurs upon VEGF signaling inhibition.

Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages

Directory of Open Access Journals (Sweden)

Orlando A

2013-04-01

Full Text Available Antonina Orlando,1 Francesca Re,1 Silvia Sesana,1 Ilaria Rivolta,1 Alice Panariti,1 Davide Brambilla,2 Julien Nicolas,2 Patrick Couvreur,2 Karine Andrieux,2 Massimo Masserini,1 Emanuela Cazzaniga1 1Department of Health Sciences, University of Milano-Bicocca, Monza, Italy; 2Institut Galien Paris Sud, University Paris-Sud, Châtenay-Malabry, France Background: As part of a project designing nanoparticles for the treatment of Alzheimer’s disease, we have synthesized and characterized a small library of nanoparticles binding with high affinity to the β-amyloid peptide and showing features of biocompatibility in vitro, which are important properties for administration in vivo. In this study, we focused on biocompatibility issues, evaluating production of nitric oxide by cultured human umbilical vein endothelial cells and macrophages, used as models of cells which would be exposed to nanoparticles after systemic administration. Methods: The nanoparticles tested were liposomes and solid lipid nanoparticles carrying phosphatidic acid or cardiolipin, and PEGylated poly(alkyl cyanoacrylate nanoparticles (PEG-PACA. We measured nitric oxide production using the Griess method as well as phosphorylation of endothelial nitric oxide synthase and intracellular free calcium, which are biochemically related to nitric oxide production. MTT viability tests and caspase-3 detection were also undertaken. Results: Exposure to liposomes did not affect the viability of endothelial cells at any concentration tested. Increased production of nitric oxide was detected only with liposomes carrying phosphatidic acid or cardiolipin at the highest concentration (120 µg/mL, together with increased synthase phosphorylation and intracellular calcium levels. Macrophages exposed to liposomes showed a slightly dose-dependent decrease in viability, with no increase in production of nitric oxide. Exposure to solid lipid nanoparticles carrying phosphatidic acid decreased viability in

Radiosensitization of hypoxic tumor cells in vitro by nitric oxide

International Nuclear Information System (INIS)

Griffin, Robert J.; Makepeace, Carol M.; Hur, Won-Joo; Song, Chang W.

1996-01-01

Purpose: The effects of nitric oxide (NO) on the radiosensitivity of SCK tumor cells in oxic and hypoxic environments in vitro were studied. Methods and Materials: NO was delivered to cell suspensions using the NO donors 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), and a spermine/nitric oxide complex (SPER/NO), which release NO at half-lives of 2.1 min and 39 min at pH 7.4, respectively. The cells were suspended in media containing DEA/NO or SPER/NO for varying lengths of time under oxic or hypoxic conditions, irradiated, and the clonogenicity determined. Results: Both compounds markedly radiosensitized the hypoxic cells. The drug enhancement ratios (DER) for 0.1, 1.0, and 2.0 mM DEA/NO were 2.0, 2.3 and 3.0, respectively, and those for 0.1, 1.0, and 2.0 mM SPER/NO were 1.6, 2.3, and 2.8, respectively. Aerobic cells were not radiosensitized by DEA/NO or SPER/NO. When DEA/NO and SPER/NO were incubated in solution overnight to allow release of NO, they were found to have no radiosensitizing effect under hypoxic or oxic conditions indicating the sensitization by the NO donors was due to the NO molecule released from these drugs. At the higher concentrations, SPER/NO was found to be cytotoxic in aerobic conditions but not in hypoxic conditions. DEA/NO was only slightly toxic to the cells in both aerobic and hypoxic conditions. Conclusions: NO released from NO donors DEA/NO and SPER/NO is as effective as oxygen to radiosensitize hypoxic cells in vitro. Its application to the radiosensitization of hypoxic cells in solid tumors remains to be investigated

Nitric oxide in health and disease of the respiratory system

NARCIS (Netherlands)

Ricciardolo, Fabio L. M.; Sterk, Peter J.; Gaston, Benjamin; Folkerts, Gert

2004-01-01

During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO

L-Arginine Increases Cytotoxicity in Irradiated Ehrlich Carcinoma Cell Line: Possible Potential Role of Nitric Oxide

International Nuclear Information System (INIS)

Noaman, E.

2008-01-01

Cancer cells possess nitric oxide syntheses (NOS) which metabolize L-Arginine (L-Arg) for producing nitric oxide (NO) The present study investigates the relations between NO and ionizing radiation in the Ehrlich ascites carcinoma (EAC) cell line. NOS activity was stimulated by exposure of cells to L-Arg just after irradiation. L-Arg (5 m M) supply led to an increase in ionizing radiation induced cytotoxicity (% of viability 18± 3 %) whereas, neither L-Arg itself nor ionizing irradiation caused cell death at the doses used in this study. Also, cells were treated either with L-Thio citrulline (L-Thio), an irreversible inhibitor of NOS or with exogenous superoxide dismutase (SOD) and catalase. L-Thio and SOD prevented L-Arg mediated deleterious effects on Irradiated cells, whereas catalase was ineffective. Intracellular antioxidant enzyme activity was also determined. Ionizing radiation + L-Arg stress altered the activity of catalase (66 % decrease) and glutathione peroxidase (83 % decrease). Our findings demonstrated that L-Arg induces increase the radiation-mediated deleterious effects in Ehrlich ascites carcinoma cells cytotoxicity and that the ratio NO/ O 2 plays a key role in these processes. NO could participate the deleterious effect of irradiation, in conjugation with others reactive oxygen species (ROS) produced during the oxidation of intracellular components by ionizing radiation (dose 6 Gy)

Inhibition of nitric oxide synthase expression in activated microglia and peroxynitrite scavenging activity by Opuntia ficus indica var. saboten.

Science.gov (United States)

Lee, Ming Hong; Kim, Jae Yeon; Yoon, Jeong Hoon; Lim, Hyo Jin; Kim, Tae Hee; Jin, Changbae; Kwak, Wie-Jong; Han, Chang-Kyun; Ryu, Jae-Ha

2006-09-01

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO-), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. A butanol fraction obtained from 50% ethanol extracts of Opuntia ficus indica var. saboten (Cactaceae) stem (SK OFB901) and its hydrolysis product (SK OFB901H) inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50 15.9, 4.2 microg/mL, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at higher than 30 microg/mL as observed by western blot analysis and RT-PCR experiment. They also inhibited the degradation of I-kappaB-alpha in activated microglia. Moreover, they showed strong activity of peroxynitrite scavenging in a cell free bioassay system. These results imply that Opuntia ficus indica may have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity. Copyright (c) 2006 John Wiley & Sons, Ltd.

[Studies on the oxidation reaction of octanol-2 with nitric acid by infrared spectroscopy].

Science.gov (United States)

Zhang, G; Zhao, G; Wang, Y; Zhang, Q; Zhang, S; Lu, F

1998-04-01

In this paper, the reaction process of oxidation of octanol-2 with nitric acid has been studied by IR spectroscopy. It is found that the main components of non-sapoifiable matter are different in different oxidation degrees. The relation between oxidation products and the amount of nitric acid are investigated,the reaction mechanism has also been studied. Experimental results show that the oxidation process of octanol-2 is as follows: first, octanol-2 is oxidated to octanone-2, or to nitrate, nitrite and nitrile copmpounds, then these compounds are reoxidated to caproic acid in the meantime some by-products, such as valeric, enanthic acids are also found in oxidated products.

Involvement of nitric oxide in anticompulsive-like effect of agmatine on marble-burying behaviour in mice.

Science.gov (United States)

Gawali, Nitin B; Chowdhury, Amrita A; Kothavade, Pankaj S; Bulani, Vipin D; Nagmoti, Dnyaneshwar M; Juvekar, Archana R

2016-01-05

In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder (OCD), patients with OCD exhibit higher plasma nitrate levels, and drugs useful in OCD influence nitric oxide. Agmatine is a polyamine and widely distributed in mammalian brain which interacts with nitrergic systems. Hence, the present study was carried out to understand the involvement of nitrergic systems in the anticompulsive-like effect of agmatine. We used marble-burying behaviour (MBB) of mice as the animal model of OCD, and nitric oxide levels in hippocampus (HC) and cortex homogenate were measured. Results revealed that, agmatine (20 and 40mg/kg, i.p) significantly inhibited the MBB. Intraperitoneal administration of nitric oxide enhancers viz. nitric oxide precursor - l-arginine (l-ARG) (400mg/kg and 800mg/kg) increased MBB as well as brain nitrites levels, whereas treatment with N(G)-nitro-l-arginine methyl ester (l-NAME) neuronal nitric oxide synthase inhibitor (30mg/kg and 50mg/kg, i.p.) and 7-nitroindazole (7-NI) (20mg/kg and 40mg/kg) attenuated MBB and nitrites levels in brain. Further, in combination studies, the anticompulsive-like effect of agmatine (20mg/kg, ip) was exacerbated by prior administration of l-ARG (400mg/kg) and conversely l-NAME (15mg/kg) or 7-NI (10.0mg/kg) attenuated OCD-like behaviour with HC and cortex changes in the levels of NO. None of the above treatment had any significant influence on locomotor activity. In conclusion, Agmatine is effective in ameliorating the compulsive-like behaviour in mice which appears to be related to nitric oxide in brain. Copyright © 2015 Elsevier B.V. All rights reserved.

Total Glucosides of Paeonia lactiflora Pall Suppress Nitric Oxide ...

African Journals Online (AJOL)

iNOS) expression and ... Keywords: Total glucosides, Paeonia lactiflora, Nitric oxide, iNOs, Nuclear factor-κB. Tropical Journal of Pharmaceutical Research ... Nuclear factor (NF)-κB is the key transcriptional factor regulating iNOS gene transcription.

Regulation and Turnover of Nitric Oxide by Phytoglobins in Plant Cell Responses

DEFF Research Database (Denmark)

Igamberdiev, Abir U; Hebelstrup, Kim; Stasolla, Claudio

2016-01-01

The involvement of phytoglobins in the metabolism of nitric oxide (NO) and reactive nitrogen species (RNS) produced during stress, plant growth, and development is discussed. The action of phytoglobin expression upon NO leads to the maintenance of redox status, minimization of the damage from...... to the mobility of both NO and phytohormones, plants developed strategies to regulate specific cell hormonal actions to permit differentiation during development and to respond to stress. Phytoglobins are the agents responsible for differential cellular responses to hormones that use NO as a signal transduction...... reactive oxygen and nitrogen species in the cytoplasm of the cell, and regulation of hormonal and stress responses. NO scavenging is achieved via phytoglobins, and it can also involve S-nitrosoglutathione reductase and a direct interaction of NO with superoxide anion followed by detoxification of formed...

Simultaneous Laser-induced Fluorescence of Nitric Oxide and Atomic Oxygen in the Hypersonic Materials Environment Test System Arcjet Facility

Science.gov (United States)

Johansen, Craig; Lincoln, Daniel; Bathel, Brett; Inman, Jennifer; Danehy, Paul

2014-01-01

Simultaneous nitric oxide (NO) and atomic oxygen (O) laser induced fluorescence (LIF) experiments were performed in the Hypersonic Materials Environmental Test System (HYMETS) facility at the NASA Langley Research Center. The data serves as an experimental database for validation for chemical and thermal nonequilibrium models used in hypersonic flows. Measurements were taken over a wide range of stagnation enthalpies (6.7 - 18.5 MJ/kg) using an Earth atmosphere simulant with a composition of 75% N2, 20% O2, and 5% Ar (by volume). These are the first simultaneous measurements of NO and O LIF to be reported in literature for the HYMETS facility. The maximum O LIF mean signal intensity was observed at a stagnation enthalpy of approximately 12 MJ/kg while the maximum NO LIF mean signal intensity was observed at a stagnation enthalpy of 6.7 MJ/kg. Experimental results were compared to simple fluorescence model that assumes equilibrium conditions in the plenum and frozen chemistry in the isentropic nozzle expansion (Mach 5). The equilibrium calculations were performed using CANTERA v2.1.1 with 16 species. The fluorescence model captured the correlation in mean O and NO LIF signal intensities over the entire range of stagnation enthalpies tested. Very weak correlations between single-shot O and NO LIF intensities were observed in the experiments at all of the stagnation enthalpy conditions.

Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms With Acute Rejection in Liver Transplant Recipients.

Science.gov (United States)

Azarpira, Negar; Namazi, Soha; Malahi, Sayan; Kazemi, Kourosh

2016-06-01

Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients. We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02). Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

Hydrogen Peroxide- and Nitric Oxide-mediated Disease Control of Bacterial Wilt in Tomato Plants

Directory of Open Access Journals (Sweden)

Jeum Kyu Hong

2013-12-01

Full Text Available Reactive oxygen species (ROS generation in tomato plants by Ralstonia solanacearum infection and the role of hydrogen peroxide (H₂O₂ and nitric oxide in tomato bacterial wilt control were demonstrated. During disease development of tomato bacterial wilt, accumulation of superoxide anion (O₂− and H₂O₂ was observed and lipid peroxidation also occurred in the tomato leaf tissues. High doses of H₂O₂and sodium nitroprusside (SNP nitric oxide donor showed phytotoxicity to detached tomato leaves 1 day after petiole feeding showing reduced fresh weight. Both H₂O₂and SNP have in vitro antibacterial activities against R. solanacearum in a dose-dependent manner, as well as plant protection in detached tomato leaves against bacterial wilt by 10⁶ and 10⁷ cfu/ml of R. solanacearum. H₂O₂- and SNP-mediated protection was also evaluated in pots using soil-drench treatment with the bacterial inoculation, and relative ‘area under the disease progressive curve (AUDPC’ was calculated to compare disease protection by H₂O₂ and/or SNP with untreated control. Neither H₂O₂ nor SNP protect the tomato seedlings from the bacterial wilt, but H₂O₂+ SNP mixture significantly decreased disease severity with reduced relative AUDPC. These results suggest that H₂O₂ and SNP could be used together to control bacterial wilt in tomato plants as bactericidal agents.

Remote Sensing the Thermosphere's State Using Emissions From Carbon Dioxide and Nitric Oxide

Science.gov (United States)

Weimer, D. R.; Mlynczak, M. G.; Doornbos, E.

2017-12-01

Measurements of emissions from nitric oxide and carbon dioxide in the thermosphere have strong correlations with properties that are very useful to the determination of thermospheric densities. We have compared emissions measured with the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) satellite with neutral density measurements from the Challenging Mini-satellite Payload (CHAMP), the Gravity Recovery and Climate Experiment (GRACE), the Ocean Circulation Explorer (GOCE), and the three Swarm satellites, spanning a time period of over 15 years. It has been found that nitric oxide emissions match changes in the exospheric temperatures that have been derived from the densities through use of the Naval Reasearch Laboratory Mass Spectrometer, Incoherent Scatter Radar Extended Model (NRLMSISE-00) thermosphere model. Similarly, our results indicate that the carbon dioxide emissions have annual and semiannual oscillations that correlate with changes in the amount of oxygen in the thermosphere, also determined by use of the NRLMSISE-00 model. These annual and semi-annual variations are found to have irregular amplitudes and phases, which make them very difficult to accurately predict. Prediction of exospheric temperatures through the use of geomagnetic indices also tends to be inexact. Therefore, it would be possible and very useful to use measurements of the thermosphere's infrared emissions for real-time tracking of the thermosphere's state, so that more accurate calculations of the density may be obtained.

Premotor nitric oxide synthase immunoreactive pathway connecting lumbar segments with the ventral motor nucleus of the cervical enlargement in the dog.

Science.gov (United States)

Marsala, Jozef; Lukácová, Nadezda; Cízková, Dása; Lukác, Imrich; Kuchárová, Karolína; Marsala, Martin

2004-03-01

In this study we investigate the occurrence and origin of punctate nitric oxide synthase immunoreactivity in the neuropil of the ventral motor nucleus in C7-Th1 segments of the dog spine, which are supposed to be the terminal field of an ascending premotor propriospinal nitric oxide synthase-immunoreactive pathway. As the first step, nitric oxide synthase immunohistochemistry was used to distinguish nitric oxide synthase-immunoreactive staining of the ventral motor nucleus. Dense, punctate nitric oxide synthase immunoreactivity was found on control sections in the neuropil of the ventral motor nucleus. After hemisection at Th10-11, axotomy-induced retrograde changes consisting in a strong upregulation of nitric oxide synthase-containing neurons were found mostly unilaterally in lamina VIII, the medial part of lamina VII and in the pericentral region in all segments of the lumbosacral enlargement. Concurrently, a strong depletion of the punctate nitric oxide synthase immunopositivity in the neuropil of the ventral motor nucleus ipsilaterally with the hemisection was detected, thus revealing that an uncrossed ascending premotor propriospinal pathway containing a fairly high number of nitric oxide synthase-immunoreactive fibers terminates in the ventral motor nucleus. Application of the retrograde fluorescent tracer Fluorogold injected into the ventral motor nucleus and analysis of alternate sections processed for nitric oxide synthase immunocytochemistry revealed the presence of Fluorogold-labeled and nitric oxide synthase-immunoreactive axons in the ventrolateral funiculus and in the lateral and medial portions of the ventral column throughout the thoracic and upper lumbar segments. A noticeable number of Fluorogold-labeled and nitric oxide synthase-immunoreactive somata detected on consecutive sections were found in the lumbosacral enlargement, mainly in laminae VIII-IX, the medial part of lamina VII and in the pericentral region (lamina X), ipsilaterally with the

Interaction between neuronal nitric oxide synthase signaling and temperature influences sarcoplasmic reticulum calcium leak: role of nitroso-redox balance.

Science.gov (United States)

Dulce, Raul A; Mayo, Vera; Rangel, Erika B; Balkan, Wayne; Hare, Joshua M

2015-01-02

Although nitric oxide (NO) signaling modulates cardiac function and excitation-contraction coupling, opposing results because of inconsistent experimental conditions, particularly with respect to temperature, confound the ability to elucidate NO signaling pathways. Here, we show that temperature significantly modulates NO effects. To test the hypothesis that temperature profoundly affects nitroso-redox equilibrium, thereby affecting sarcoplasmic reticulum (SR) calcium (Ca(2+)) leak. We measured SR Ca(2+) leak in cardiomyocytes from wild-type (WT), NO/redox imbalance (neuronal nitric oxide synthase-deficient mice-1 [NOS1(-/-)]), and hyper S-nitrosoglutathione reductase-deficient (GSNOR(-/-)) mice. In WT cardiomyocytes, SR Ca(2+) leak increased because temperature decreased from 37°C to 23°C, whereas in NOS1(-/-) cells, the leak suddenly increased when the temperature surpassed 30°C. GSNOR(-/-) cardiomyocytes exhibited low leak throughout the temperature range. Exogenously added NO had a biphasic effect on NOS1(-/-) cardiomyocytes; reducing leak at 37°C but increasing it at subphysiological temperatures. Oxypurinol and Tempol diminished the leak in NOS1(-/-) cardiomyocytes. Cooling from 37°C to 23°C increased reactive oxygen species generation in WT but decreased it in NOS1(-/-) cardiomyocytes. Oxypurinol further reduced reactive oxygen species generation. At 23°C in WT cells, leak was decreased by tetrahydrobiopterin, an essential NOS cofactor. Cooling significantly increased SR Ca(2+) content in NOS1(-/-) cells but had no effect in WT or GSNOR(-/-). Ca(2+) leak and temperature are normally inversely proportional, whereas NOS1 deficiency reverses this effect, increasing leak and elevating reactive oxygen species production because temperature increases. Reduced denitrosylation (GSNOR deficiency) eliminates the temperature dependence of leak. Thus, temperature regulates the balance between NO and reactive oxygen species which in turn has a major effect on SR

In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla.

Science.gov (United States)

Kim, N Y; Pae, H O; Ko, Y S; Yoo, J C; Choi, B M; Jun, C D; Chung, H T; Inagaki, M; Higuchi, R; Kim, Y C

1999-10-01

Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting.

Nitric oxide inhibits glycogen synthesis in isolated rat hepatocytes

NARCIS (Netherlands)

Sprangers, F.; Sauerwein, H. P.; Romijn, J. A.; van Woerkom, G. M.; Meijer, A. J.

1998-01-01

There is increasing evidence for the existence of intrahepatic regulation of glucose metabolism by Kupffer cell products. Nitric oxide (NO) is known to inhibit gluconeogenic flux through pyruvate carboxylase and phosphoenolpyruvate carboxykinase. However, NO may also influence glucose metabolism at

Low blood flow at onset of moderate intensity exercise does not limit muscle oxygen uptake

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Mortensen, Stefan Peter; Saltin, Bengt

2010-01-01

The effect of low blood flow at onset of moderate intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5 minute one-legged knee-extensor exercise bout (24+/-1 (+/-S.D.) W) without (CON) and with (double blockade; DB) arterial infusion of i....... Additionally, prostanoids and/or NO appear to play important roles in elevating skeletal muscle blood flow in the initial phase of exercise. Key words: Oxygen delivery, oxygen extraction, nitric oxide, prostanoids.......The effect of low blood flow at onset of moderate intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5 minute one-legged knee-extensor exercise bout (24+/-1 (+/-S.D.) W) without (CON) and with (double blockade; DB) arterial infusion...... of inhibitors of nitric oxide synthase (NOS; L-NMMA) and cyclooxygenase (COX; indomethacin) in order to inhibit the synthesis of nitric oxide (NO) and prostanoids, respectively.. Leg blood flow and leg oxygen delivery throughout exercise was 25-50 % lower (P

Nitric Oxide: A Multitasked Signaling Gas in Plants

KAUST Repository

Domingos, Patricia

2014-12-01

Nitric oxide (NO) is a gaseous reactive oxygen species (ROS) that has evolved as a signaling hormone in many physiological processes in animals. In plants it has been demonstrated to be a crucial regulator of development, acting as a signaling molecule present at each step of the plant life cycle. NO has also been implicated as a signal in biotic and abiotic responses of plants to the environment. Remarkably, despite this plethora of effects and functional relationships, the fundamental knowledge of NO production, sensing, and transduction in plants remains largely unknown or inadequately characterized. In this review we cover the current understanding of NO production, perception, and action in different physiological scenarios. We especially address the issues of enzymatic and chemical generation of NO in plants, NO sensing and downstream signaling, namely the putative cGMP and Ca2+ pathways, ion-channel activity modulation, gene expression regulation, and the interface with other ROS, which can have a profound effect on both NO accumulation and function. We also focus on the importance of NO in cell–cell communication during developmental processes and sexual reproduction, namely in pollen tube guidance and embryo sac fertilization, pathogen defense, and responses to abiotic stress.

Nitric oxide synthase gene G298 allele

International Nuclear Information System (INIS)

Nagib El-Kilany, Galal E.; Nayel, Ehab; Hazzaa, Sahar

2004-01-01

Background: Nitric oxide (NO) has an important effect on blood pressure, arterial wall, and the basal release of endothelial NO in hypertension (HPN) may be reduced. Until now, there is no solid data revealing the potential role of the polymorphism of the nitric oxide synthase gene (NOS) in patients with HPN and microvascular angina. Aim: The aim of the present study is to investigate the gene of endothelial nitric oxide synthase (eNOS), as the polymorphism of this gene may be a putative candidate for HPN and initiate the process of atherosclerosis. Methods: Sixty participants were recruited for this study; 50 were hypertensive patients complaining of chest pain [30 of them have electrocardiogram (EKG) changes of ischemia], 20 had isolated HPN, and 10 healthy volunteers served as control. All patients underwent stress myocardial perfusion imaging (MPI) and coronary angiography. Genotyping of eNOS for all patients and controls was performed. The linkages between HPN, microvascular angina and eNOS gene polymorphism were investigated. Results: MPI and coronary angiography revealed that 15 patients had chest pain with true ischemia and reversible myocardial perfusion defects (multiple and mild) but normal epicardial coronary arteries (microvascular angina), while 15 patients had significant coronary artery disease (CAD), and 20 hypertensive patients showed normal perfusion scan and coronary angiography. The prevalence of the NOS G 298 allele was higher in the hypertensive group with microvascular angina (documented by MPI) than it was among the control participants (P<.005). The eNOS allele was significantly higher in the hypertensive group than in the control participants, but there was no significant difference in homozygote mutants among hypertensive participants, x-syndrome and patients with CAD. Conclusion: eNOS gene polymorphism is proved to be an important etiology in microvascular angina (x-syndrome) among hypertensive patients. In addition, the eNOS mutant

Storm Time Variation of Radiative Cooling by Nitric Oxide as Observed by TIMED-SABER and GUVI

Science.gov (United States)

Bharti, Gaurav; Sunil Krishna, M. V.; Bag, T.; Jain, Puneet

2018-02-01

The variation of O/N2 (reference to N2 column density 1017 cm-2) and nitric oxide radiative emission flux exiting the thermosphere have been studied over the Northern Hemisphere during the superstorm event of 7-12 November 2004. The data have been obtained from Global Ultraviolet Imager (GUVI) and Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) on board the National Aeronautics and Space Administration (NASA)'s Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics (TIMED) satellite. The NO radiative flux is observed to show an anti-correlation with O/N2 on a global scale. Both NO radiative flux and O/N2 ratio show equatorward motion with maximum penetration in western longitude sectors. A local variation of O, O2, and N2 densities have been calculated using NRLMSISE-00 model over a midlatitude location (55°N,180°E). On a local scale, model calculated O/O2 and O/N2 ratios are found to follow the observations made by GUVI. The collisional excitation of NO with atomic oxygen is the most dominant process for the total cooling rate. The SABER-retrieved NO cooling rate (CR) at a local site suggests an enhancement during the storm period with the peak emission rate closely correlated to the progression of the storm. The peak emission altitude of NO CR moves upward during the main phase of the storm. The NO abundance has been calculated by using cooling rate and Nitric Oxide Empirical Model (NOEM) model. Both these suggest a vary large (3-15 times) increase in NO density during the storm, which is required to account the changes in NO radiative flux. A similar kind of enhancement in NO abundance is also noticed in Student Nitric Oxide Explorer observations during intense geomagnetic storms.

Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75

OpenAIRE

Cáceres, Lucía; Necakov, Aleksandar S.; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J.H.; Krause, Henry M.

2011-01-01

Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer part...

Neuronal nitric oxide synthase-deficient mice have impaired Renin release but normal blood pressure

DEFF Research Database (Denmark)

Sällström, Johan; Carlström, Mattias; Jensen, Boye L

2008-01-01

BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodiu......-116; doi:10.1038/ajh.2007.16American Journal of Hypertension (2008) 21 111-116; doi:10.1038/ajh.2007.16....

Role of nitric oxide in methamphetamine neurotoxicity: protection by 7-nitroindazole, an inhibitor of neuronal nitric oxide synthase.

Science.gov (United States)

Di Monte, D A; Royland, J E; Jakowec, M W; Langston, J W

1996-12-01

The role of nitric oxide (NO.) in the neurotoxic effects of methamphetamine (METH) was evaluated using 7-nitroindazole (7-NI), a potent inhibitor of neuronal nitric oxide synthase. Treatment of mice with 7-NI (50 mg/kg) almost completely counteracted the loss of dopamine, 3,4-dihydroxyphenylacetic acid, and tyrosine hydroxylase immunoreactivity observed 5 days after four injections of 10 or 7.5 mg/kg METH. With the higher dose of METH, this protection at 5 days occurred despite the fact that combined administration of METH and 7-NI significantly increased lethality and exacerbated METH-induced dopamine release (as indicated by a greater dopamine depletion at 90 min and 1 day). Combined treatment with 4 x 10 mg/kg METH and 7-NI also slightly increased the body temperature of mice as compared with METH alone. Thus, the neuroprotective effects of 7-NI are independent from lethality, are not likely to be related to a reduction of METH-induced dopamine release, and are not due to a decrease in body temperature. These results indicate that NO. formation is an important step leading to METH neurotoxicity, and suggest that the cytotoxic properties of NO. may be directly involved in dopaminergic terminal damage.

The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone.

Science.gov (United States)

Arnold, Robyn E; Weigent, Douglas A

2003-01-01

Growth hormone (GH) is produced by immunocompetent cells and has been implicated in the regulation of a multiplicity of functions in the immune system involved in growth and activation. However, the actions of endogenous or lymphocyte GH and its contribution to immune reactivity when compared with those of serum or exogenous GH are still unclear. In the present study, we overexpressed lymphocyte GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role of endogenous GH in nitric oxide (NO) production and response to genotoxic stress. Western blot analysis demonstrated that the levels of GH increased approximately 40% in cells overexpressing GH (GHo) when compared with cells with vector alone. The results also show a substantial increase in NO production in cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L-NMMA), an L-arginine analogue that competitively inhibits all three isoforms of nitric oxide synthase (NOS). No evidence was obtained to support an increase in peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS protein expression, whereas endothelial nitric oxide synthase and neuronal nitric oxide synthase protein levels were essentially unchanged. In addition, cells overexpressing GH showed increased arginine transport ability and intracellular arginase activity when compared with control cells. GH overexpression appeared to protect cells from the toxic effects of the DNA alkylating agent methyl methanesulfonate. This possibility was suggested by maintenance of the mitochondrial transmembrane potential in cells overexpressing GH when compared with control cells that could be blocked by L-NMMA. Taken together, the data support the notion that lymphocyte GH, independently of the GH receptor, may play a key role in the survival of lymphocytes exposed to stressful stimuli via the production of NO.

Comparison the effects of nitric oxide and spermidin pretreatment on alleviation of salt stress in chamomile plant (Matricaria recutita L.

Directory of Open Access Journals (Sweden)

Fazelian Nasrin

2012-08-01

Full Text Available Salt stress is an important environmental stress that produces reactive oxygen species in plants and causes oxidative injuries. In this investigation, salt stress reduced the shoot and root length, while increased the content of malondealdehyde, Hydrogen peroxide, and the activity of Ascorbate peroxidase andguaiacol peroxidase. Pretreatment of chamomile plants under salt stress with sodium nitroprussideand Spermidin caused enhancement of growth parameters and reduction of malondealdehyde and Hydrogen peroxide content. Pretreatment of plants with sodium nitroprusside remarkably increased Ascorbate peroxidase activity, while Spermidin pre-treatment significantly increased guaiacol peroxidase activity. Application of sodium nitroprusside or Spermidin with Methylene blue which is known to block cyclic guanosine monophosphate signaling pathway, reduced the protective effects of sodium nitroprussideand Spermidin in plants under salinity condition. The result of this study indicated that Methylene blue could partially and entirely abolish the protective effect of Nitric oxide on some physiological parameter. Methylene blue also has could reduce the alleviation effect of Spermidin on some of parameters in chamomile plant under salt stress, so with comparing the results of this study it seems that Spermidin probably acts through Nitric oxide pathway, but the use of 2-4- carboxyphenyl- 4,4,5,5- tetramethyl-imidazoline-1-oxyl-3-oxide is better to prove.

Modulation of glucose uptake in adipose tissue by nitric oxide ...

Indian Academy of Sciences (India)

Madhu

ion-dependent breakdown and trans-nitrosation reactions are ... [McGrowder D, Ragoobirsingh D and Brown P 2006 Modulation of glucose uptake in adipose tissue by nitric oxide-generating ... Briefly, nicotinamide (Sigma Chemical Co.,.

Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin

NARCIS (Netherlands)

Lechner, Matthias; Lirk, Philipp; Rieder, Josef

2005-01-01

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid l-arginine. iNOS-derived NO plays an important role in numerous physiological (e.g. blood pressure regulation, wound repair and host defence mechanisms) and pathophysiological

Controlling Oxygen Mobility in Ruddlesden–Popper Oxides

Directory of Open Access Journals (Sweden)

Dongkyu Lee

2017-03-01

Full Text Available Discovering new energy materials is a key step toward satisfying the needs for next-generation energy conversion and storage devices. Among the various types of oxides, Ruddlesden–Popper (RP oxides (A2BO4 are promising candidates for electrochemical energy devices, such as solid oxide fuel cells, owing to their attractive physicochemical properties, including the anisotropic nature of oxygen migration and controllable stoichiometry from oxygen excess to oxygen deficiency. Thus, understanding and controlling the kinetics of oxygen transport are essential for designing optimized materials to use in electrochemical energy devices. In this review, we first discuss the basic mechanisms of oxygen migration in RP oxides depending on oxygen nonstoichiometry. We then focus on the effect of changes in the defect concentration, crystallographic orientation, and strain on the oxygen migration in RP oxides. We also briefly review their thermal and chemical stability. Finally, we conclude with a perspective on potential research directions for future investigation to facilitate controlling oxygen ion migration in RP oxides.

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

African Journals Online (AJOL)

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway.

Nitric oxide nanoparticles

Science.gov (United States)

Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.

2012-01-01

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO-np may be an effective addition to our armament for deep soft tissue infections. PMID:22286699

Localization of nitric oxide synthase in human skeletal muscle

DEFF Research Database (Denmark)

Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

1996-01-01

The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...

Water vapour and carbon dioxide decrease nitric oxide readings

NARCIS (Netherlands)

vanderMark, TW; Kort, E; Meijer, RJ; Postma, DS; Koeter, GH

Measurement of nitric oxide levels in exhaled ah-is commonly performed using a chemiluminescence detector. However, water vapour and carbon dioxide affect the chemiluminescence process, The influence of these gases at the concentrations present in exhaled air has not vet been studied. For this in

Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

Science.gov (United States)

Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

2012-08-01

Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

Dependence of nitrite oxidation on nitrite and oxygen in low-oxygen seawater

Science.gov (United States)

Sun, Xin; Ji, Qixing; Jayakumar, Amal; Ward, Bess B.

2017-08-01

Nitrite oxidation is an essential step in transformations of fixed nitrogen. The physiology of nitrite oxidizing bacteria (NOB) implies that the rates of nitrite oxidation should be controlled by concentration of their substrate, nitrite, and the terminal electron acceptor, oxygen. The sensitivities of nitrite oxidation to oxygen and nitrite concentrations were investigated using 15N tracer incubations in the Eastern Tropical North Pacific. Nitrite stimulated nitrite oxidation under low in situ nitrite conditions, following Michaelis-Menten kinetics, indicating that nitrite was the limiting substrate. The nitrite half-saturation constant (Ks = 0.254 ± 0.161 μM) was 1-3 orders of magnitude lower than in cultivated NOB, indicating higher affinity of marine NOB for nitrite. The highest rates of nitrite oxidation were measured in the oxygen depleted zone (ODZ), and were partially inhibited by additions of oxygen. This oxygen sensitivity suggests that ODZ specialist NOB, adapted to low-oxygen conditions, are responsible for apparently anaerobic nitrite oxidation.

Nitric oxide synthase in the gill of Atlantic salmon: colocalization with and inhibition of Na+,K+-ATPase

DEFF Research Database (Denmark)

Ebbesson, Lars O E; Tipsmark, Christian K; Holmqvist, Bo

2005-01-01

We investigated the relationship between nitric oxide (NO) and Na(+),K(+)-ATPase (NKA) in the gill of anadromous Atlantic salmon. Cells containing NO-producing enzymes were revealed by means of nitric oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphor...

Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

Science.gov (United States)

Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

2015-12-15

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

Science.gov (United States)

Fricchione, Gregory; Stefano, George B

2005-05-01

Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Nitric oxide in the stress axis.

Science.gov (United States)

López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

1998-10-01

In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

Thermal-grating contributions to degenerate four-wave mixing in nitric oxide

International Nuclear Information System (INIS)

Danehy, P.M.; Paul, P.H.; Farrow, R.L.

1995-01-01

We report investigations of degenerate four-wave mixing (DFWM) line intensities in the A 2 Σ + left-arrow X 2 Π electronic transitions of nitric oxide. Contributions from population gratings (spatially varying perturbations in the level populations of absorbing species) and thermal gratings (spatially varying perturbations in the overall density) were distinguished and compared by several experimental and analytical techniques. For small quantities of nitric oxide in a strongly quenching buffer gas (carbon dioxide), we found that thermal-grating contributions dominated at room temperature for gas pressures of ∼0.5 atm and higher. In a nearly nonquenching buffer (nitrogen) the population-grating mechanism dominated at pressures of ∼1.0 atm and lower. At higher temperatures in an atmospheric-pressure methane/air flame, population gratings of nitric oxide also dominated. We propose a simple model for the ratio of thermal- to population-grating scattering intensities that varies as P 4 T -4.4 . Preliminary investigations of the temperature dependence and detailed studies of the pressure dependence are in agreement with this model. Measurements of the temporal evolution and the peak intensity of isolated thermal-grating signals are in detailed agreement with calculations based on a linearized hydrodynamic model [J. Opt. Soc. Am. B 12, 384 (1995)]. copyright 1995 Optical Society of America

Cellular inactivation of nitric oxide induces p53-dependent ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1595-1603 ... Cellular inactivation of nitric oxide induces p53-dependent apoptosis in ... apoptosis induced by a selective iNOS inhibitor, N-[(3-aminomethyl) benzyl] acetamidine (1400W), .... and nitrate. ... Nitrite production was measured in culture media.

17β-Estradiol reduces nitric oxide production in the Guinea pig cochlea.

Science.gov (United States)

Heinrich, U-R; Brieger, J; Striedter, C; Fischer, I; Schmidtmann, I; Li, H; Mann, W J; Helling, K

2013-11-01

Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17β-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17β-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17β-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17β-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17β-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection. © Georg Thieme Verlag KG Stuttgart · New York.

Endothelial Nitric Oxide Synthase Phosphorylation at Threonine 495 and Mitochondrial Reactive Oxygen Species Formation in Response to a High H2O2 Concentration

DEFF Research Database (Denmark)

Guterbaum, Thomas Jeremy; Braunstein, Thomas Hartig; Fossum, A

2013-01-01

Hydrogen peroxide (H₂O₂) is produced in vessels during ischemia/reperfusion and during inflammation, both leading to vascular dysfunction. We investigated cellular pathways involved in endothelial nitric oxide synthase (eNOS) phosphorylation at Threonine 495 (Thr(495)) in human umbilical vein end...

Exercise promotes collateral artery growth mediated by monocytic nitric oxide.

Science.gov (United States)

Schirmer, Stephan H; Millenaar, Dominic N; Werner, Christian; Schuh, Lisa; Degen, Achim; Bettink, Stephanie I; Lipp, Peter; van Rooijen, Nico; Meyer, Tim; Böhm, Michael; Laufs, Ulrich

2015-08-01

Collateral artery growth (arteriogenesis) is an important adaptive response to hampered arterial perfusion. It is unknown whether preventive physical exercise before limb ischemia can improve arteriogenesis and modulate mononuclear cell function. This study aimed at investigating the effects of endurance exercise before arterial occlusion on MNC function and collateral artery growth. After 3 weeks of voluntary treadmill exercise, ligation of the right femoral artery was performed in mice. Hindlimb perfusion immediately after surgery did not differ from sedentary mice. However, previous exercise improved perfusion restoration ≤7 days after femoral artery ligation, also when exercise was stopped at ligation. This was accompanied by an accumulation of peri-collateral macrophages and increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) in hindlimb collateral and in MNC of blood and spleen. Systemic monocyte and macrophage depletion by liposomal clodronate but not splenectomy attenuated exercise-induced perfusion restoration, collateral artery growth, peri-collateral macrophage accumulation, and upregulation of iNOS. iNOS-deficient mice did not show exercise-induced perfusion restoration. Transplantation of bone marrow-derived MNC from iNOS-deficient mice into wild-type animals inhibited exercise-induced collateral artery growth. In contrast to sedentary controls, thrice weekly aerobic exercise training for 6 months in humans increased peripheral blood MNC iNOS expression. Circulating mononuclear cell-derived inducible nitric oxide is an important mediator of exercise-induced collateral artery growth. © 2015 American Heart Association, Inc.

Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis.

Science.gov (United States)

Hyde, Embriette R; Andrade, Fernando; Vaksman, Zalman; Parthasarathy, Kavitha; Jiang, Hong; Parthasarathy, Deepa K; Torregrossa, Ashley C; Tribble, Gena; Kaplan, Heidi B; Petrosino, Joseph F; Bryan, Nathan S

2014-01-01

The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis.

Directory of Open Access Journals (Sweden)

Embriette R Hyde

Full Text Available The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

Science.gov (United States)

Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide

Directory of Open Access Journals (Sweden)

Heikal L

2016-08-01

Full Text Available Lamia Heikal,1 Pietro Ghezzi,1 Manuela Mengozzi,1 Blanka Stelmaszczuk,2 Martin Feelisch,2 Gordon AA Ferns1 1Brighton and Sussex Medical School, Falmer, Brighton, 2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton, UK Abstract: The cytoprotective effects of erythropoietin (EPO and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP, were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2 and hypoxic (1% O2 conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay, we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions. Furthermore, EPO protected bovine aortic endothelial cells from staurosporine-induced apoptosis under hypoxic conditions. The priming effect of hypoxia was associated with stabilization of hypoxia inducible factor-1α, EPO receptor upregulation, and decreased Ser-1177 phosphorylation of endothelial nitric oxide synthase (NOS; the effect of hypoxia on the latter was rescued by EPO. Hypoxia was associated with a reduction in nitric oxide (NO production as assessed by its oxidation products, nitrite and nitrate, consistent with the oxygen requirement for endogenous production of NO by endothelial NOS. However, while EPO did not affect NO formation in normoxia, it markedly increased NO production, in a manner sensitive to NOS inhibition, under hypoxic conditions. These data are consistent with the notion that the tissue-protective actions of EPO-related cytokines in pathophysiological settings associated with poor oxygenation are mediated by NO. These findings may be particularly relevant to atherogenesis and postangioplasty restenosis. Keywords

Catalyst for Decomposition of Nitrogen Oxides

Science.gov (United States)

Schryer, David R. (Inventor); Jordan, Jeffrey D. (Inventor); Akyurtlu, Ates (Inventor); Akyurtlu, Jale (Inventor)

2015-01-01

This invention relates generally to a platinized tin oxide-based catalyst. It relates particularly to an improved platinized tin oxide-based catalyst able to decompose nitric oxide to nitrogen and oxygen without the necessity of a reducing gas.

Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.

Science.gov (United States)

Gupta, N; Bhargava, V K; Pandhi, P

2000-05-01

The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

Oxygen transport by oxygen potential gradient in dense ceramic oxide membranes

Energy Technology Data Exchange (ETDEWEB)

Maiya, P.S.; Balachandran, U.; Dusek, J.T.; Mieville, R.L. [Argonne National Lab., IL (United States). Energy Technology Div.; Kleefisch, M.S.; Udovich, C.A. [Amoco Exploration/Production, Naperville, IL (United States)

1996-05-01

Numerous studies have been conducted in recent years on the partial oxidation of methane to synthesis gas (syngas: CO + H{sub 2}) with air as the oxidant. In partial oxidation, a mixed-oxide ceramic membrane selectively transports oxygen from the air; this transport is driven by the oxygen potential gradient. Of the several ceramic materials the authors have tested, a mixed oxide based on the Sr-Fe-Co-O system has been found to be very attractive. Extensive oxygen permeability data have been obtained for this material in methane conversion experiments carried out in a reactor. The data have been analyzed by a transport equation based on the phenomenological theory of diffusion under oxygen potential gradients. Thermodynamic calculations were used to estimate the driving force for the transport of oxygen ions. The results show that the transport equation deduced from the literature describes the permeability data reasonably well and can be used to determine the diffusion coefficients and the associated activation energy of oxygen ions in the ceramic membrane material.

Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase

International Nuclear Information System (INIS)

Yang, Jin Won; Yoon, Se Young; Oh, Soo Jin; Kim, Sang Kyum; Kang, Keon Wook

2006-01-01

Algal fucoidan is a marine sulfated polysaccharide with a wide variety of biological activities including anti-thrombotic and anti-inflammatory effects. This study evaluated the effect of fucoidan on the expression of inducible nitric oxide synthase (iNOS) in a macrophage cell line, RAW264.7. Low concentration range of fucoidan (10 μg/ml) increased the basal expression level of iNOS in quiescent macrophages. However, we found for the first time that fucoidan inhibited the release of nitric oxide (NO) in RAW264.7 cells stimulated with lipopolysaccharide (LPS). Western blot analysis revealed that fucoidan suppressed the LPS-induced expression of the inducible nitric oxide synthase (iNOS) gene. Moreover, the activation of both nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) are key steps in the transcriptional activation of the iNOS gene. Here, it was revealed that fucoidan selectively suppressed AP-1 activation, and that the activation of AP-1 appears to be essential for the induction of iNOS in activated macrophages. This inhibitory effect on AP-1 activation by fucoidan might be associated with its NO blocking and anti-inflammatory effects

Detection of nitric acid and nitric oxides in the terrestrial atmosphere in the middle-infrared spectral region

Directory of Open Access Journals (Sweden)

M. I. Blecka

1996-11-01

Full Text Available A proposal for combined space and ground-based observations of the vertical distributions and the column densities of nitric acid and nitric oxide concentrations in the earth's atmosphere is discussed. We focus on the aspects that are particular to the idea of correlative measurements: geometrical considerations, simulations of the solar absorption spectra in the middle-infrared region corresponding to the different observational geometries, and the associated retrieval methods. These studies are done specifically for the Belgian-French experiment MIRAS (MIR Infrared Atmospheric Spectrometer onboard the Russian Space Station MIR and correlative ground-based FTIR measurements in the Tatra mountains.

Nitric oxide protects carbon assimilation process of watermelon from boron-induced oxidative injury.

Science.gov (United States)

Farag, Mohamed; Najeeb, Ullah; Yang, Jinghua; Hu, Zhongyuan; Fang, Zhang Ming

2017-02-01

Nitric oxide (NO) mediates plant response to a variety of abiotic stresses; however, limited information is available on its effect on boron (B)-stressed watermelon plants. The present study investigates the mechanism through which NO protects watermelon seedlings from B deficiency and toxicity stresses. Five days old watermelon seedlings were exposed to B (0, 0.5 and 10 mg L -1 ) alone or with 75 μmole of NO donor sodium nitroprusside (SNP) for 30 days. Both low and high B concentrations in the media altered nutrient accumulation and impaired various physiological processes of watermelon seedlings, leading to a significant reduction in biomass production. The plants exposed to B deficient or toxic concentrations had 66 and 69% lower shoot dry weight, respectively compared with optimum B levels. B toxicity-induced growth inhibition of watermelon seedlings was associated with high B translocation to shoot tissues, which caused lipid membrane peroxidation (12% increase) and chlorophyll destruction (25% reduction). In contrast, B deficiency accelerated generation of reactive oxygen species (ROS), specifically OH -1 and induced cellular oxidative injury. Exogenously applied SNP promoted leaf chlorophyll, photosynthesis and consequently biomass production in B-stressed watermelon seedlings by reducing B accumulation, lipid membrane peroxidation and ROS generation. It also activated antioxidant enzymes such as SOD, POD and APX, and protected the seedlings from ROS-induced cellular burst. Copyright © 2016. Published by Elsevier Masson SAS.

Nitric oxide and chronic colitis

Directory of Open Access Journals (Sweden)

Matthew B Grisham

1996-01-01

Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

Nitric oxide radical scavenging potential of some Elburz medicinal ...

African Journals Online (AJOL)

Some plants scavenge nitric oxide (NO) with high affinity. For this purpose, forty extracts from 26 medicinal plants, growing extensively in Elburz mountains, were evaluated for their NO scavenging activity. Total phenolic and flavonoid contents of these extracts were also measured by Folin Ciocalteu and AlCl3 colorimetric ...

Nitric oxide in acute brain injury: a pilot study of NO(x) concentrations in human brain microdialysates and their relationship with energy metabolism.

Science.gov (United States)

Carpenter, Keri L H; Timofeev, Ivan; Al-Rawi, Pippa G; Menon, David K; Pickard, John D; Hutchinson, Peter J

2008-01-01

This pilot microdialysis study in acute brain injury patients assessed the relationship between nitric oxide products (total nitrite plus nitrate, termed NO(x)) and energy-related molecules: glucose, lactate, pyruvate, glutamate and glycerol. Twelve patients (11 major head-injury and one subarachnoid haemorrhage) were studied, 11 of which had single catheters and one had two catheters, in the cerebral cortex. Catheters were perfused at 0.3 microL/min with CNS perfusion fluid. Collection vials were changed hourly. Microdialysates were analysed for energy-related molecules on a CMA600 or ISCUS analyser, and for NO(x) using a purge vessel (VCl3 plus HCl at 95 degrees C, purged with nitrogen) connected to a Sievers NOA 280i analyser. The mean of mean NO(x) concentration (+/- SD) for the 13 catheters was 32.7 +/- 16.8 micromol/L, and the lactate/ pyruvate ratio was 38.6 +/- 20.1. Increasing NO(x) concentrations correlated significantly with decreasing lactate/ pyruvate ratio (Spearman r = -0.79, p = 0.0065), with decreasing lactate concentration (r = -0.59, p = 0.042), and with increasing glucose concentration (r = 0.71, p = 0.018). These pilot data suggest that in injured brains, higher concentrations of nitric oxide are associated with more favourable metabolism. Nitric oxide may act beneficially by increasing blood flow and delivery of oxygen and glucose. Further patients are being recruited.

Oxygen potentials of transuranium oxides

International Nuclear Information System (INIS)

Haruyoshi Otobe; Mituso Akabori; Arai Yasuo; Kazuo Minato

2008-01-01

The oxygen potentials of pyrochlore-type Pu 2 Zr 2 O 7+y , fluorite-type (Pu 0.5 Zr 0.5 )O 2-x and AmO 2-x have been measured by the electromotive force (EMF) method with a zirconia solid-electrolyte. The oxygen potentials of these oxides were reviewed. The phase relations, microstructure, equilibrium state of these oxides were discussed, referring to the isothermal curve of the oxygen potentials. (authors)

How to protect liver graft with nitric oxide

Institute of Scientific and Technical Information of China (English)

Hassen Ben Abdennebi; Mohamed Amine Zaoualí; Izabel Alfany-Fernandez; Donia Tabka; Joan Roselló-Catafau

2011-01-01

Organ preservation and ischemia reperfusion injury associated with liver transplantation play an important role in the induction of graft injury. One of the earliest events associated with the reperfusion injury is endothelial cell dysfunction. It is generally accepted that endothelial nitric oxide synthase (e-NOS) is cell-protective by mediating vasodilatation, whereas inducible nitric oxide synthase mediates liver graft injury after transplantation. We conducted a critical review of the literature evaluating the potential applications of regulating and promoting e-NOS activity in liver preservation and transplantation, showing the most current evidence to support the concept that enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate graft liver preservation, as well as preventing subsequent graft reperfusion injury. This review deals mainly with the beneficial effects of promoting "endogenous" pathways for NO generation, via e-NOS inducer drugs in cold preservation solution, surgical strategies such as ischemic preconditioning, and alternative "exogenous" pathways that focus on the enrichment of cold storage liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary of the liver physiology and cell signalling mechanisms that account for explaining the e-NOS protective effects in liver preservation and transplantation.

Direct and controllable nitric oxide delivery into biological media and living cells by a pin-to-hole spark discharge (PHD) plasma

Energy Technology Data Exchange (ETDEWEB)

Dobrynin, D; Friedman, G [Electrical and Computer Engineering Department, College of Engineering, Drexel University, Philadelphia, PA (United States); Arjunan, K; Clyne, A Morss [School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA (United States); Fridman, A, E-mail: alisam@coe.drexel.edu [Department of Mechanical Engineering and Mechanics, College of Engineering, Drexel University, Philadelphia, PA (United States)

2011-02-23

Nitric oxide has great potential for improving wound healing through both inflammatory and vascularization processes. Nitric oxide can be produced in high concentrations by atmospheric pressure thermal plasmas. We measured the physical characteristics and nitric oxide production of a pin-to-hole spark discharge (PHD) plasma, as well as plasma-produced nitric oxide delivery into liquid and endothelial cells. The plasma temperature was calculated as 9030 {+-} 320 K by the Boltzmann method, which was adequate to produce nitric oxide, although the average gas temperature was near room temperature. The plasma produced significant UV radiation and hydrogen peroxide, but these were prevented from reaching the cells by adding a straight or curved tube extension to the plasma device. Plasma-produced nitric oxide in gas reached 2000 ppm and rapidly diffused into liquid and cells. Cells remained viable following plasma treatment and showed a linear increase in cGMP concentration with plasma treatment, indicating an intracellular functional response to PHD plasma NO. These data suggest that this plasma may provide a novel method for delivering NO locally and directly for enhanced wound healing.

Direct and controllable nitric oxide delivery into biological media and living cells by a pin-to-hole spark discharge (PHD) plasma

International Nuclear Information System (INIS)

Dobrynin, D; Friedman, G; Arjunan, K; Clyne, A Morss; Fridman, A

2011-01-01

Nitric oxide has great potential for improving wound healing through both inflammatory and vascularization processes. Nitric oxide can be produced in high concentrations by atmospheric pressure thermal plasmas. We measured the physical characteristics and nitric oxide production of a pin-to-hole spark discharge (PHD) plasma, as well as plasma-produced nitric oxide delivery into liquid and endothelial cells. The plasma temperature was calculated as 9030 ± 320 K by the Boltzmann method, which was adequate to produce nitric oxide, although the average gas temperature was near room temperature. The plasma produced significant UV radiation and hydrogen peroxide, but these were prevented from reaching the cells by adding a straight or curved tube extension to the plasma device. Plasma-produced nitric oxide in gas reached 2000 ppm and rapidly diffused into liquid and cells. Cells remained viable following plasma treatment and showed a linear increase in cGMP concentration with plasma treatment, indicating an intracellular functional response to PHD plasma NO. These data suggest that this plasma may provide a novel method for delivering NO locally and directly for enhanced wound healing.

Effects of 1400W and/or nitroglycerin on renal oxygenation and kidney function during endotoxaemia in anaesthetized rats

NARCIS (Netherlands)

Johannes, Tanja; Mik, Egbert G.; Klingel, Karin; Goedhart, Peter T.; Zanke, Christof; Nohé, Boris; Dieterich, Hans-Jürgen; Unertl, Klaus E.; Ince, Can

2009-01-01

1. The pathogenesis of acute renal failure (ARF) in sepsis is multifactorial. The role of nitric oxide (NO) in septic ARF has been a source of controversy. We hypothesized that endotoxaemia-induced exacerbation of inducible nitric oxide synthase (iNOS)-related NO release impairs renal oxygenation

Continuous electrochemical monitoring of nitric oxide production in murine macrophage cell line RAW 264.7

Czech Academy of Sciences Publication Activity Database

Pekarová, Michaela; Králová, Jana; Kubala, Lukáš; Číž, Milan; Lojek, Antonín; Gregor, Č.; Hrbáč, J.

2009-01-01

Roč. 394, č. 5 (2009), s. 1497-1504 ISSN 1618-2642 R&D Projects: GA AV ČR(CZ) 1QS500040507 Grant - others:GA ČR(CZ) GP524/05/P135 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : nitric oxide * macrophage s RAW 264.7 * nitric oxide sensor Subject RIV: BO - Biophysics Impact factor: 3.480, year: 2009

Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets.

Science.gov (United States)

Jana, Pradipta; Maiti, Smarajit; Kahn, Nighat N; Sinha, Asru K

2015-04-01

Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd1 of 6.0 × 10 mol/l and 39 ± 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet.

Variation of nitric oxide levels in imported Plasmodium falciparum ...

African Journals Online (AJOL)

SERVER

2008-03-18

Mar 18, 2008 ... Nitric oxide (NO) has been recognized during the past two decades as one of the most versatile players in the immune system. Even though the molecular mechanisms responsible by the naturally acquired immunity against malaria are still to be clarified, the production of NO seems to play an important role.

Melatonin inhibits endothelin-1 and induces endothelial nitric oxide ...

African Journals Online (AJOL)

Although, I/R augmented the endothelin-1 (ET-1) gene expression and the level of big endothelin-1 (big ET-1) in liver tissue, melatonin attenuated these increases. Conversely, non-significant decrease in endothelial nitric oxide synthase (eNOS) mRNA expression in I/R group was significantly elevated by melatonin in ...

Vascular endothelial growth factor up-regulates the expression of intracellular adhesion molecule-1 in retinal endothelial cells via reactive oxygen species, but not nitric oxide

Institute of Scientific and Technical Information of China (English)

ZHANG Xiao-ling; WEN Liang; CHEN Yan-jiong; ZHU Yi

2009-01-01

Background The vascular endothelial growth factor (VEGF) is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 (ICAM-1) is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells (ECs) is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs.Methods Bovine retinal ECs (BRECs) were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF (100 ng/ml) and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase (eNOS) were detected using Western blotting. Griess reaction was used to detect nitric oxide (NO).Results Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C (PKC) altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase (PI3K) or reactive oxygen species (ROS) significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased.Conclusion ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.

Analysis of genetic variation of inducible nitric oxide synthase and ...

African Journals Online (AJOL)

The genetic diversity of 100 Malaysian native chickens was investigated using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) for two candidate genes: inducible nitric oxide synthase (INOS) and natural resistance-associated macrophage protein 1 (NRAMP1). The two genes were selected ...

The nitric oxide prodrug JS-K and its structural analogues as cancer therapeutic agents.

Science.gov (United States)

Maciag, Anna E; Saavedra, Joseph E; Chakrapani, Harinath

2009-09-01

Nitric oxide (NO) prodrugs of the diazeniumdiolate class are routinely used as reliable sources of nitric oxide in chemical and biological laboratory settings. O(2)-(2,4-dinitrophenyl) diazeniumdiolates, which are derivatized forms of ionic diazeniumdiolates, have been found to show potent anti-proliferative activity in a variety of cancer cells, presumably through the effects of NO. One important member of this class of diazeniumdiolates, O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K), has shown promise as a novel cancer therapeutic agent in a number of animal models. This review describes the developments in chemical and biochemical characterization and structure-activity relationship of JS-K and its analogues. In addition, some molecular mechanistic insights into the observed anti-proliferative activity of JS-K are discussed. Finally, a structural motif is presented for O(2)-(aryl) diazeniumdiolate nitric oxide prodrugs that show potency comparable with that of JS-K.

Fourier transform infrared studies of reduction of nitric oxide by ethylene over V[sub 2]O[sub 5] layered on ZrO[sub 2

Energy Technology Data Exchange (ETDEWEB)

Ohno, Takashi; Hatayama, Fumikazu (School of Allied Medical Sciences, Kobe University, Kobe (Japan)); Toda, Yoshio (Department of Industrial Chemistry, Osaka Prefectural Technical College, Osaka (Japan)); Konishi, Shoichiro; Miyata, Hisashi (Department of Applied Chemistry, University of Osaka Prefecture, Osaka (Japan))

1994-12-31

The reduction mechanism of nitric oxide by ethylene in the presence or absence of oxygen on mono- and multi-layer V[sub 2]O[sub 5]/ZrO[sub 2] and the structures of the catalysts under reaction conditions have been studied by Fourier transform infrared spectroscopy as well as by analysis of the reaction products. For the reaction of a mixture of NO+C[sub 2]H[sub 4], only carboxylate species were observed at higher temperatures, although at lower temperatures nitrate species were formed. No bands due to a complex of NO+C[sub 2]H[sub 4] were observed. From the results, it is proposed that ethylene is oxidized by the catalyst to form carbon dioxide via carbonyl and carboxylate species and nitric oxide reoxidizes the catalyst to form nitrogen. The quantitative analysis of the V=O band in the region of 1100-900 cm[sup -1] by band shape analysis indicates that only the surface V=O species in the top layer of the catalyst interacts with the adsorbed species

Calcium mobilization in HeLa cells induced by nitric oxide.

Science.gov (United States)

Huang, Yimei; Zheng, Liqin; Yang, Hongqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

2014-01-01

Nitric oxide (NO) has been proposed to be involved in tumor growth and metastasis. However, the mechanism by which nitric oxide modulates cancer cell growth and metastasis on cellular and molecular level is still not fully understood. This work utilized confocal microscopy and fluorescence microplate reader to investigate the effects of exogenous NO on the mobilization of calcium, which is one of the regulators of cell migration, in HeLa cells. The results show that NO elevates calcium in concentration-dependent manner in HeLa cells. And the elevation of calcium induced by NO is due to calcium influx and calcium release from intracellular calcium stores. Moreover, calcium release from intracellular stores is dominant. Furthermore, calcium release from mitochondria is one of the modulation pathways of NO. These findings would contribute to recognizing the significance of NO in cancer cell proliferation and metastasis. © Wiley Periodicals, Inc.

Nitric oxide and HSV vaginal infection in BALB/c mice

International Nuclear Information System (INIS)

Benencia, Fabian; Gamba, Gisela; Cavalieri, Hernan; Courreges, Maria Cecilia; Benedetti, Ruben; Villamil, Soledad Maria; Massouh, Ernesto Jorge

2003-01-01

Here we study the role of nitric oxide in the vaginal infection of Balb/c mice with herpes simplex virus type 2. Inducible nitric oxide synthase (iNOS) mRNA was detected by RT-PCR in vaginal tissue and inguinal lymph nodes early postinfection. iNOS was also found to be activated in cells recovered from vaginal washings of infected animals. Animals treated with aminoguanidine (AG), an iNOS inhibitor, showed a dose-dependent increase in vaginal pathology after viral infection compared to controls. Viral titers in vaginal washings and vaginas were higher in AG-treated mice. Treated animals presented higher PMN counts in vaginal washings compared to controls. Histopathology studies revealed a profound inflammatory exudate in vaginal tissue of treated animals. Finally, RT-PCR analysis showed increased expression of the chemokines MIP-2 and RANTES in vaginal tissue and inguinal lymph nodes of these animals

Synthesis of N-(Methoxycarbonylthienylmethylthioureas and Evaluation of Their Interaction with Inducible and Neuronal Nitric Oxide Synthase

Directory of Open Access Journals (Sweden)

Michael D. Threadgill

2010-04-01

Full Text Available Two isomeric N-(methoxycarbonylthienylmethylthioureas were synthesised by a sequence of radical bromination of methylthiophenecarboxylic esters, substitution with trifluoroacetamide anion, deprotection, formation of the corresponding isothiocyanates and addition of ammonia. The interaction of these new thiophene-based thioureas with inducible and neuronal nitric oxide synthase was evaluauted. These novel thienylmethylthioureas stimulated the activity of inducible Nitric Oxide Synthase (iNOS.

Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms.

Science.gov (United States)

Amour, Julien; Brzezinska, Anna K; Jager, Zachary; Sullivan, Corbin; Weihrauch, Dorothee; Du, Jianhai; Vladic, Nikolina; Shi, Yang; Warltier, David C; Pratt, Phillip F; Kersten, Judy R

2010-03-01

Endothelial nitric oxide synthase activity is regulated by (6R-)5,6,7,8-tetrahydrobiopterin (BH4) and heat shock protein 90. The authors tested the hypothesis that hyperglycemia abolishes anesthetic preconditioning (APC) through BH4- and heat shock protein 90-dependent pathways. Myocardial infarct size was measured in rabbits in the absence or presence of APC (30 min of isoflurane), with or without hyperglycemia, and in the presence or absence of the BH4 precursor sepiapterin. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells cultured in normal (5.5 mm) or high (20 mm) glucose conditions, with or without sepiapterin (10 or 100 microm). APC decreased myocardial infarct size compared with control experiments (26 +/- 6% vs. 46 +/- 3%, respectively; P < 0.05), and this action was blocked by hyperglycemia (43 +/- 4%). Sepiapterin alone had no effect on infarct size (46 +/- 3%) but restored APC during hyperglycemia (21 +/- 3%). The beneficial actions of sepiapterin to restore APC were blocked by the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (47 +/- 2%) and the BH4 synthesis inhibitor N-acetylserotonin (46 +/- 3%). Isoflurane increased nitric oxide production to 177 +/- 13% of baseline, and this action was attenuated by high glucose concentrations (125 +/- 6%). Isoflurane increased, whereas high glucose attenuated intracellular BH4/7,8-dihydrobiopterin (BH2) (high performance liquid chromatography), heat shock protein 90-endothelial nitric oxide synthase colocalization (confocal microscopy) and endothelial nitric oxide synthase activation (immunoblotting). Sepiapterin increased BH4/BH2 and dose-dependently restored nitric oxide production during hyperglycemic conditions (149 +/- 12% and 175 +/- 9%; 10 and 100 microm, respectively). The results indicate that tetrahydrobiopterin and heat shock protein 90-regulated endothelial nitric oxide synthase activity play a central

Nanomaterials-based electrochemical sensors for nitric oxide

International Nuclear Information System (INIS)

Dang, Xueping; Hu, Hui; Wang, Shengfu; Hu, Shengshui

2015-01-01

Electrochemical sensing has been demonstrated to represent an efficient way to quantify nitric oxide (NO) in challenging physiological environments. A sensing interface based on nanomaterials opens up new opportunities and broader prospects for electrochemical NO sensors. This review (with 141 refs.) gives a general view of recent advances in the development of electrochemical sensors based on nanomaterials. It is subdivided into sections on (i) carbon derived nanomaterials (such as carbon nanotubes, graphenes, fullerenes), (ii) metal nanoparticles (including gold, platinum and other metallic nanoparticles); (iii) semiconductor metal oxide nanomaterials (including the oxides of titanium, aluminum, iron, and ruthenium); and finally (iv) nanocomposites (such as those formed from carbon nanomaterials with nanoparticles of gold, platinum, NiO or TiO 2 ). The various strategies are discussed, and the advances of using nanomaterials and the trends in NO sensor technology are outlooked in the final section. (author)

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid ...

African Journals Online (AJOL)

patients after intra-articular injection of sodium hyaluronate, while the effect is insignificant in severe patients. Thus, sodium hyaluronate can effectively improve nitric oxide levels in synovial fluid, reduce ..... Modern Med Health, 2014; 1:.

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid ...

African Journals Online (AJOL)

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid in Osteoarthritis Patients ... Tropical Journal of Pharmaceutical Research ... and moderate phase patients after intra-articular injection of sodium hyaluronate, while the effect ...

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

Science.gov (United States)

Erdmann, Jeanette; Stark, Klaus; Esslinger, Ulrike B; Rumpf, Philipp Moritz; Koesling, Doris; de Wit, Cor; Kaiser, Frank J; Braunholz, Diana; Medack, Anja; Fischer, Marcus; Zimmermann, Martina E; Tennstedt, Stephanie; Graf, Elisabeth; Eck, Sebastian; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Brænne, Ingrid; Nöthen, Markus M; Hofmann, Per; Braund, Peter S; Mergia, Evanthia; Reinhard, Wibke; Burgdorf, Christof; Schreiber, Stefan; Balmforth, Anthony J; Hall, Alistair S; Bertram, Lars; Steinhagen-Thiessen, Elisabeth; Li, Shu-Chen; März, Winfried; Reilly, Muredach; Kathiresan, Sekar; McPherson, Ruth; Walter, Ulrich; Ott, Jurg; Samani, Nilesh J; Strom, Tim M; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert

2013-12-19

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.

Ribavirin in Cancer Immunotherapies: Controlling Nitric Oxide Augments Cytotoxic Lymphocyte Function

Directory of Open Access Journals (Sweden)

Richard E. Kast

2003-01-01

Full Text Available Either ribavirin (RBV or cyclophosphamide (CY can shift an immune response from Th2 toward a Thi cytokine profile. CY is used in this role in various current cancer immunotherapy attempts but with mixed success. More potent and reliable immunoadjuvants and Th1 response biasing methods are needed. RBV is used today mainly to augment interferon-alpha treatment of hepatitis C. RBV shifts an immune response from Th2 toward Th1 more effectively than CY and may be a safe and useful adjuvant for current cancer immunotherapeutic efforts. RBV is thought to act by inhibition of tetrahydrobiopterin synthesis. Tetrahydrobiopterin is an essential cofactor for all known isoforms of nitric oxide synthase. Lowered nitric oxide favors Th1 development as high levels favor Th2 weighting.

Enhanced biogenic emissions of nitric oxide and nitrous oxide following surface biomass burning

Science.gov (United States)

Anderson, Iris C.; Levine, Joel S.; Poth, Mark A.; Riggan, Philip J.

1988-01-01

Recent measurements indicate significantly enhanced biogenic soil emissions of both nitric oxide (NO) and nitrous oxide (N2O) following surface burning. These enhanced fluxes persisted for at least six months following the burn. Simultaneous measurements indicate enhanced levels of exchangeable ammonium in the soil following the burn. Biomass burning is known to be an instantaneous source of NO and N2O resulting from high-temperature combustion. Now it is found that biomass burning also results in significantly enhanced biogenic emissions of these gases, which persist for months following the burn.

Nitric oxide heme interactions in nitrophorin from Cimex lectularius

Energy Technology Data Exchange (ETDEWEB)

Christmann, R.; Auerbach, H., E-mail: auerbach@physik.uni-kl.de [University of Kaiserslautern, Department of Physics (Germany); Berry, R. E.; Walker, F. A. [The University of Arizona, Department of Chemistry and Biochemistry (United States); Schünemann, V. [University of Kaiserslautern, Department of Physics (Germany)

2016-12-15

The nitrophorin from the bedbug Cimex lectularius (cNP) is a nitric oxide (NO) carrying protein. Like the nitrophorins (rNPs) from the kissing bug Rhodnius prolixus, cNP forms a stable heme Fe(III)-NO complex, where the NO can be stored reversibly for a long period of time. In both cases, the NPs are found in the salivary glands of blood-sucking bugs. The insects use the nitrophorins to transport the NO to the victim’s tissues, resulting in vasodilation and reduced blood coagulation. However, the structure of cNP is significantly different to those of the rNPs from Rhodnius prolixus. Furthermore, the cNP can bind a second NO molecule to the proximal heme cysteine when present at higher concentrations. High field Mössbauer spectroscopy on {sup 57}Fe enriched cNP complexed with NO shows reduction of the heme iron and formation of a ferrous nitric oxide (Fe(II)-NO) complex. Density functional theory calculations reproduce the experimental Mössbauer parameters and confirm this observation.

Requirement of argininosuccinate lyase for systemic nitric oxide production.

Science.gov (United States)

Erez, Ayelet; Nagamani, Sandesh C S; Shchelochkov, Oleg A; Premkumar, Muralidhar H; Campeau, Philippe M; Chen, Yuqing; Garg, Harsha K; Li, Li; Mian, Asad; Bertin, Terry K; Black, Jennifer O; Zeng, Heng; Tang, Yaoping; Reddy, Anilkumar K; Summar, Marshall; O'Brien, William E; Harrison, David G; Mitch, William E; Marini, Juan C; Aschner, Judy L; Bryan, Nathan S; Lee, Brendan

2011-11-13

Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases.

A comparison of blood nitric oxide metabolites and hemoglobin functional properties among diving mammals.

Science.gov (United States)

Fago, Angela; Parraga, Daniel Garcia; Petersen, Elin E; Kristensen, Niels; Giouri, Lea; Jensen, Frank B

2017-03-01

The ability of marine mammals to hunt prey at depth is known to rely on enhanced oxygen stores and on selective distribution of blood flow, but the molecular mechanisms regulating blood flow and oxygen transport remain unresolved. To investigate the molecular mechanisms that may be important in regulating blood flow, we measured concentration of nitrite and S-nitrosothiols (SNO), two metabolites of the vasodilator nitric oxide (NO), in the blood of 5 species of marine mammals differing in their dive duration: bottlenose dolphin, South American sea lion, harbor seal, walrus and beluga whale. We also examined oxygen affinity, sensitivity to 2,3-diphosphoglycerate (DPG) and nitrite reductase activity of the hemoglobin (Hb) to search for possible adaptive variations in these functional properties. We found levels of plasma and red blood cells nitrite similar to those reported for terrestrial mammals, but unusually high concentrations of red blood cell SNO in bottlenose dolphin, walrus and beluga whale, suggesting enhanced SNO-dependent signaling in these species. Purified Hbs showed similar functional properties in terms of oxygen affinity and sensitivity to DPG, indicating that reported large variations in blood oxygen affinity among diving mammals likely derive from phenotypic variations in red blood cell DPG levels. The nitrite reductase activities of the Hbs were overall slightly higher than that of human Hb, with the Hb of beluga whale, capable of longest dives, having the highest activity. Taken together, these results underscore adaptive variations in circulatory NO metabolism in diving mammals but not in the oxygenation properties of the Hb. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigation of the direct and indirect electrochemical oxidation of hydrazine in nitric acid medium on platinum

International Nuclear Information System (INIS)

Cames, B.

1997-01-01

In nuclear fuel processing by the PUREX process, the purification of plutonium in nitric acid medium requires the oxidation of Pu(III) to Pu(IV), and of hydrazinium nitrate to nitrogen. The study helped to characterize the electrochemical behavior of the oxidation of hydrazinium nitrate and the reduction of nitric acid to nitrous acid, a compound which can chemically oxidize hydrazinium nitrate and Pu(III). Electro-analytical studies on polycrystalline platinum showed that hydrazine is oxidized in two potential zones, which depend on the surface texture of the platinum anode. Electrolysis in separate compartments, carried out in medium-acid media (2 and 4 mo/l) in the potential zone where these processes take place, showed that, at 0.9 V/ECS, the hydrazine oxidation reactions involved are: a four-electron process (75 %) with nitrogen formation and a one-electron process (25 %) with formation of nitrogen and ammonium ion. By contrast, electrolysis carried out at 0.65 V/ECS (with reactivation of the electrode at - 0.2 V/ECS to remove the poison from the platinum) allowed the selective oxidation of hydrazine to nitrogen by the four-electron reaction. Nitric acid can only be reduced to nitrous acid in the absence of hydrazine. For medium-acid media (≤ 6 mol/l), this reaction takes place at potentials below - 0.2 V/ECS. However, the production rate of nitrous acid (partial order 0 with respect to nitric acid) is very low compared with the values obtained for strongly-acid media (6 to 10 mol/l) at the potential of - 0.1 V/ECS. Note that, in concentrated nitric medium, the selectivity of the reduction reaction is 47 to 85 % for nitrous acid, depending on the nitric acid concentration (6 to 10 mol/l) and the potential imposed (- 0.1 ≤ E ≤ 0.6 V/ECS). A kinetic study helped to determine the hydrazine oxidation rates as a function of the operating conditions. In all cases, the reaction rate is of partial order 0 with respect to hydrazine. These studies accordingly

Variation of nitric oxide levels in imported Plasmodium falciparum ...

African Journals Online (AJOL)

SERVER

2008-03-18

Mar 18, 2008 ... ISSN 1684–5315 © 2008 Academic Journals. Full Length Research Paper. Variation of nitric oxide levels in imported Plasmodium falciparum malaria episodes. De Sousa, Karina*, Silva, Marcelo S. and Tavira, Luís T. Instituto de Higiene e Medicina Tropical, Centro de Malária e outras Doenças Tropicais, ...

Serum Iron and Nitric Oxide Production in Trypanosoma brucei ...

African Journals Online (AJOL)

JTEkanem

reduction in the serum iron status and a modulation of nitric oxide synthase activity of T. brucei infected rats. ... inflammation and tissue damage15. ... The serum iron level was determined ... concentration or of total nitrate and nitrite ... 15. 16. 17. 18. Days. S e ru m iro n lev e l mg. /ml. Infected treated. Infected untreated. 0.

Oxidation of ruthenium thin films using atomic oxygen

Energy Technology Data Exchange (ETDEWEB)

McCoy, A.P.; Bogan, J.; Brady, A.; Hughes, G.

2015-12-31

In this study, the use of atomic oxygen to oxidise ruthenium thin films is assessed. Atomic layer deposited (ALD) ruthenium thin films (~ 3 nm) were exposed to varying amounts of atomic oxygen and the results were compared to the impact of exposures to molecular oxygen. X-ray photoelectron spectroscopy studies reveal substantial oxidation of metallic ruthenium films to RuO{sub 2} at exposures as low as ~ 10{sup 2} L at 575 K when atomic oxygen was used. Higher exposures of molecular oxygen resulted in no metal oxidation highlighting the benefits of using atomic oxygen to form RuO{sub 2}. Additionally, the partial oxidation of these ruthenium films occurred at temperatures as low as 293 K (room temperature) in an atomic oxygen environment. - Highlights: • X-ray photoelectron spectroscopy study of the oxidation of Ru thin films • Oxidation of Ru thin films using atomic oxygen • Comparison between atomic oxygen and molecular oxygen treatments on Ru thin films • Fully oxidised RuO{sub 2} thin films formed with low exposures to atomic oxygen.

Response to Reactive Nitrogen Intermediates in Mycobacterium tuberculosis: Induction of the 16-Kilodalton α-Crystallin Homolog by Exposure to Nitric Oxide Donors

OpenAIRE

Garbe, T. R.; Hibler, N. S.; Deretic, V.

1999-01-01

In contrast to the apparent paucity of Mycobacterium tuberculosis response to reactive oxygen intermediates, this organism has evolved a specific response to nitric oxide challenge. Exposure of M. tuberculosis to NO donors induces the synthesis of a set of polypeptides that have been collectively termed Nox. In this work, the most prominent Nox polypeptide, Nox16, was identified by immunoblotting and by N-terminal sequencing as the α-crystallin-related, 16-kDa small heat shock protein, sHsp16...

Nanocarriers for Nitric Oxide Delivery

Directory of Open Access Journals (Sweden)

Juliana Saraiva

2011-01-01

Full Text Available Nitric oxide (NO is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

L-arginine increases nitric oxide and attenuates pressor and heart ...

African Journals Online (AJOL)

olayemitoyin

heart rate responses to change in posture in sickle cell anemia subjects. 1 .... the standing position and measurements made immediately. Arterial ... pressure was the difference between systolic and diastolic ... Table 3. Effect of L-Arginine Supplementation on Blood Pressure Parameters, Plasma L-Arginine and Nitric Oxide.

Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn

Directory of Open Access Journals (Sweden)

Mei-Yin Lai

2018-02-01

Full Text Available Persistent pulmonary hypertension (PPHN is a consequence of failed pulmonary vascular transition at birth and leads to pulmonary hypertension with shunting of deoxygenated blood across the ductus arteriosus (DA and foramen ovale (FO resulting in severe hypoxemia, and it may eventually lead to life-threatening circulatory failure. PPHN is a serious event affecting both term and preterm infants in the neonatal intensive care unit. It is often associated with diseases such as congenital diaphragmatic hernia, meconium aspiration, sepsis, congenital pneumonia, birth asphyxia and respiratory distress syndrome. The diagnosis of PPHN should include echocardiographic evidence of increased pulmonary pressure, with demonstrable right-to-left shunt across the DA or FO, and the absence of cyanotic heart diseases. The mainstay therapy of PPHN includes treatment of underlying causes, maintenance of adequate systemic blood pressure, optimized ventilator support for lung recruitment and alveolar ventilation, and pharmacologic measures to increase pulmonary vasodilation and decrease pulmonary vascular resistance. Inhaled nitric oxide has been proved to treat PPHN successfully with improved oxygenation in 60–70% of patients and to significantly reduce the need for extracorporeal membrane oxygenation (ECMO. About 14%–46% of the survivors develop long-term impairments such as hearing deficits, chronic lung disease, cerebral palsy and other neurodevelopmental disabilities.

Nitric Oxide Release for Improving Performance of Implantable Chemical Sensors - A Review.

Science.gov (United States)

Cha, Kyoung Ha; Wang, Xuewei; Meyerhoff, Mark E

2017-12-01

Over the last three decades, there has been extensive interest in developing in vivo chemical sensors that can provide real-time measurements of blood gases (oxygen, carbon dioxide, and pH), glucose/lactate, and potentially other critical care analytes in the blood of hospitalized patients. However, clot formation with intravascular sensors and foreign body response toward sensors implanted subcutaneously can cause inaccurate analytical results. Further, the risk of bacterial infection from any sensor implanted in the human body is another major concern. To solve these issues, the release of an endogenous gas molecule, nitric oxide (NO), from the surface of such sensors has been investigated owing to NO's ability to inhibit platelet activation/adhesion, foreign body response and bacterial growth. This paper summarizes the importance of NO's therapeutic potential for this application and reviews the publications to date that report on the analytical performance of NO release sensors in laboratory testing and/or during in vivo testing.

Rocuronium Bromide Inhibits Inflammation and Pain by Suppressing Nitric Oxide Production and Enhancing Prostaglandin E2 Synthesis in Endothelial Cells.

Science.gov (United States)

Baek, Sang Bin; Shin, Mal Soon; Han, Jin Hee; Moon, Sang Woong; Chang, Boksoon; Jeon, Jung Won; Yi, Jae Woo; Chung, Jun Young

2016-12-01

Rocuronium bromide is a nondepolarizing neuromuscular blocking drug and has been used as an adjunct for relaxation or paralysis of the skeletal muscles, facilitation of endotracheal intubation, and improving surgical conditions during general anesthesia. However, intravenous injection of rocuronium bromide induces injection pain or withdrawal movement. The exact mechanism of rocuronium bromide-induced injection pain or withdrawal movement is not yet understood. We investigated whether rocuronium bromide treatment is involved in the induction of inflammation and pain in vascular endothelial cells. For this study, calf pulmonary artery endothelial (CPAE) cells were used, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot, nitric oxide detection, and prostaglandin E 2 immunoassay were conducted. Rocuronium bromide treatment inhibited endothelial nitric oxide synthase and suppressed nitric oxide production in CPAE cells. Rocuronium bromide activated cyclooxygenase-2, inducible nitric oxide synthase and increased prostaglandin E 2 synthesis in CPAE cells. Rocuronium bromide induced inflammation and pain in CPAE cells. Suppressing nitric oxide production and enhancing prostaglandin E 2 synthesis might be associated with rocuronium bromide-induced injection pain or withdrawal movement.

Auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism

Science.gov (United States)

Cai, Weiming; Hu, Liwei; Hu, Xiangyang; Cui, Dayong; Cai, Weiming

Gravitropism is the asymmetric growth or curvature of plant organs in response to gravistimulation. There is a complex signal transduction cascade which involved in the differential growth of plants in response to changes in the gravity vector. The role of auxin in gravitropism has been demonstrated by many experiments, but little is known regarding the molecular details of such effects. In our studies before, mediation of the gravitropic bending of soybean roots and rice leaf sheath bases by nitric oxide, cGMP and gibberellins, are induced by auxin. The asymmetrical distribution of nitric oxide, cGMP and gibberellins resulted from the asymmetrical synthesis of them in bending sites. In soybean roots, inhibitions of NO and cGMP synthesis reduced differential NO and cGMP accumulation respectively, which both of these effects can lead to the reduction of gravitropic bending. Gibberellin-induced OsXET, OsEXPA4 and OsRWC3 were also found involved in the gravitropic bending. These data indicated that auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism. More experiments need to prove the more detailed mechanism of them.

Immune-relevant thrombocytes of common carp undergo parasite-induced nitric oxide-mediated apoptosis.

Science.gov (United States)

Fink, Inge R; Ribeiro, Carla M S; Forlenza, Maria; Taverne-Thiele, Anja; Rombout, Jan H W M; Savelkoul, Huub F J; Wiegertjes, Geert F

2015-06-01

Common carp thrombocytes account for 30-40% of peripheral blood leukocytes and are abundant in the healthy animals' spleen, the thrombopoietic organ. We show that, ex vivo, thrombocytes from healthy carp express a large number of immune-relevant genes, among which several cytokines and Toll-like receptors, clearly pointing at immune functions of carp thrombocytes. Few studies have described the role of fish thrombocytes during infection. Carp are natural host to two different but related protozoan parasites, Trypanoplasma borreli and Trypanosoma carassii, which reside in the blood and tissue fluids. We used the two parasites to undertake controlled studies on the role of fish thrombocytes during these infections. In vivo, but only during infection with T. borreli, thrombocytes were massively depleted from the blood and spleen leading to severe thrombocytopenia. Ex vivo, addition of nitric oxide induced a clear and rapid apoptosis of thrombocytes from healthy carp, supporting a role for nitric oxide-mediated control of immune-relevant thrombocytes during infection with T. borreli. The potential advantage for parasites to selectively deplete the host of thrombocytes via nitric oxide-induced apoptosis is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction of insulin secretion in engineered liver cells by nitric oxide

Directory of Open Access Journals (Sweden)

Özcan Sabire

2007-10-01

Full Text Available Abstract Background Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs in a glucose-independent manner. In the present study we engineered liver cells to produce and secrete insulin and insulin secretion can be stimulated via the nitric oxide pathway. Results Expression of either human insulin or the beta cell specific transcription factors PDX-1, NeuroD1 and MafA in the Hepa1-6 cell line or primary liver cells via adenoviral gene transfer, results in production and secretion of insulin. Although, the secretion of insulin is not significantly increased in response to high glucose, treatment of these engineered liver cells with L-arginine stimulates insulin secretion up to three-fold. This L-arginine-mediated insulin release is dependent on the production of nitric oxide. Conclusion Liver cells can be engineered to produce insulin and insulin secretion can be induced by treatment with L-arginine via the production of nitric oxide.

Inhibition of DNA repair by whole body irradiation induced nitric oxide leads to higher radiation sensitivity in lymphocytes

International Nuclear Information System (INIS)

Sharma, Deepak; Santosh Kumar, S.; Raghu, Rashmi; Maurya, D.K.; Sainis, K.B.

2007-01-01

Full text: It is well accepted that the sensitivity of mammalian cells is better following whole body irradiation (WBI) as compared to that following in vitro irradiation. However, the underlying mechanisms are not well understood. Following WBI, the lipid peroxidation and cell death were significantly higher in lymphocytes as compared to that in vitro irradiated lymphocytes. Further, WBI treatment of tumor bearing mice resulted in a significantly higher inhibition of EL-4 cell proliferation as compared to in vitro irradiation of EL-4 cells. The DNA repair was significantly slower in lymphocytes obtained from WBI treated mice as compared to that in the cells exposed to same dose of radiation in vitro. Generation of nitric oxide following irradiation and also its role in inhibition of DNA repair have been reported, hence, its levels were estimated under both WBI and in vitro irradiation conditions. Nitric oxide levels were significantly elevated in the plasma of WBI treated mice but not in the supernatant of in vitro irradiated cells. Addition of sodium nitroprusside (SNP), a nitric oxide donor to in vitro irradiated cells inhibited the repair of DNA damage and sensitized cells to undergo cell death. It also enhanced the radiation-induced functional impairment of lymphocytes as evinced from suppression of mitogen-induced IL-2, IFN-γ and bcl-2 mRNA expression. Administration of N G -nitro-L-arginine-methyl-ester(L-NAME), a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. Our results indicated that nitric oxide plays a role in the higher radiosensitivity of lymphocytes in vivo by inhibiting repair of DNA damage

Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75.

Science.gov (United States)

Cáceres, Lucía; Necakov, Aleksandar S; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J H; Krause, Henry M

2011-07-15

Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3). Manipulation of these interactions leads to gross alterations in feeding behavior, fat deposition, and developmental timing. These neuroendocrine interactions and consequences appear to be conserved in vertebrates.

Daily life negative mood and exhaled nitric oxide in asthma.

Science.gov (United States)

Ritz, Thomas; Kullowatz, Antje; Bill, Michelle N; Rosenfield, David

2016-07-01

Psychosocial stress and negative affect have been linked to asthma exacerbations, but longitudinal studies demonstrating a daily life association between negative affect and airway nitric oxide are missing. The longitudinal association between negative mood fluctuations, exhaled nitric oxide, and lung function in asthma was examined. Self-assessments of the fraction of exhaled nitric oxide (FeNO), spirometry (forced expiratory volume in the first second, FEV1), negative mood, and daily activities were obtained from 20 patients with asthma for 2 months, resulting in 1108 assessments for the analyses (approximately 55 per patient). Concurrent and prospective associations between FeNO, FEV1, and negative mood were analyzed using mixed effects regression models for longitudinal data. Negative mood was positively associated with changes in FeNO during the same day, and to a stronger extent when prior day negative mood was included in the prediction. FeNO and negative mood were positively associated with same-day FEV1, with the latter relation being partially mediated by changes in FeNO. Associations between FeNO and FEV1 were stronger in younger patients, with earlier onset of asthma, or with lower asthma control. Findings were not changed when controlling for physical activity, medication, cold symptoms, air pollution, and hours spent outside. Daily life changes of negative mood in asthma are positively associated with FeNO changes and FeNO increases are associated with a mild bronchodilation. These findings indicate that psychological influences need to be considered when using FeNO as indicator of airway inflammation and guide for treatment decisions. Copyright © 2016 Elsevier B.V. All rights reserved.

Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

OpenAIRE

van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

2000-01-01

Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study,...

Nitric oxide synthase isoforms in spontaneous and salt hypertension

Czech Academy of Sciences Publication Activity Database

Hojná, Silvie; Kuneš, Jaroslav; Zicha, Josef

2007-01-01

Roč. 25, Suppl. 2 (2007), S 338-S 338 ISSN 0263-6352. [European Meeting on Hypertension /17./. 15.06.2007-19.06.2007, Milan] R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : nitric oxide synthase isoforms * spontaneous and salt hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

Synergistic effects between catalase inhibitors and modulators of nitric oxide metabolism on tumor cell apoptosis.

Science.gov (United States)

Scheit, Katrin; Bauer, Georg

2014-10-01

Inhibitors of catalase (such as ascorbate, methyldopa, salicylic acid and neutralizing antibodies) synergize with modulators of nitric oxide (NO) metabolism (such as arginine, arginase inhibitor, NO synthase-inducing interferons and NO dioxygenase inhibitors) in the singlet oxygen-mediated inactivation of tumor cell protective catalase. This is followed by reactive oxygen species (ROS)-dependent apoptosis induction. TGF-beta, NADPH oxidase-1, NO synthase, dual oxidase-1 and caspase-9 are characterized as essential catalysts in this process. The FAS receptor and caspase-8 are required for amplification of ROS signaling triggered by individual compounds, but are dispensable when the synergistic effect is established. Our findings explain the antitumor effects of catalase inhibitors and of compounds that target NO metabolism, as well as their synergy. These data may have an impact on epidemiological studies related to secondary plant compounds and open new perspectives for the establishment of novel antitumor drugs and for the improvement of established chemotherapeutics. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Comparison of nitric oxide binding to different pure and mixed protoporphyrin IX monolayers

NARCIS (Netherlands)

Knoben, W.; Crego-Calama, M.; Brongersma, S.H.

2012-01-01

The nitric oxide (NO) binding properties of monolayers of four different protoporphyrins IX adsorbed on aluminum oxide surfaces have been investigated. XPS and AFM results are consistent with the presence of a monolayer of porphyrins, bound to the surface by their carboxylic acid groups and with the

Kinetic analysis of nitric oxide reduction using biogas as reburning fuel

African Journals Online (AJOL)

STORAGESEVER

2009-05-18

May 18, 2009 ... Emission of nitric oxide (NO) from coal combustion continues to be a significant ... mass has been focused as a renewable fuel without CO2 addition, and researches ..... Giles DE, Som S, Aggarwal SK (2006). NOx emission ...

Variations in exhaled nitric oxide concentration after three types of dives

NARCIS (Netherlands)

van Ooij, Pieter-Jan; Houtkooper, Antoinette; van Hulst, Rob

2010-01-01

An increase in exhaled nitric oxide concentration (FENO) occurs during an exacerbation of chronic obstructive lung disease or other inflammatory processes of the airway. Raised FENO levels are also observed during normobaric, mild hyperoxic exposures, whereas after hyperbaric hyperoxic exposure the

Nitric oxide mediates insect cellular immunity via phospholipase A2 activation

Science.gov (United States)

After infection or invasion is recognized, biochemical mediators act in signaling insect immune functions. These include biogenic amines, insect cytokines, eicosanoids and nitric oxide (NO). Treating insects or isolated hemocyte populations with different mediators often leads to similar results. Se...

Nitric oxide synthase inhibition and cerebrovascular regulation

DEFF Research Database (Denmark)

Iadecola, C; Pelligrino, D A; Moskowitz, M A

1994-01-01

tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large......There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular...

Low blood flow at onset of moderate-intensity exercise does not limit muscle oxygen uptake

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Mortensen, Stefan P; Saltin, Bengt

2010-01-01

The effect of low blood flow at onset of moderate-intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5-min one-legged knee-extensor exercise bout (24 +/- 1 W, mean +/- SD) without (Con) and with (double blockade; DB) arterial infusion...... of inhibitors of nitric oxide synthase (N(G)-monomethyl-l-arginine) and cyclooxygenase (indomethacin) to inhibit the synthesis of nitric oxide and prostanoids, respectively. Leg blood flow and leg oxygen delivery throughout exercise was 25-50% lower (P ... +/- 12 vs. 262 +/- 39 ml/min). The present data demonstrate that muscle blood flow and oxygen delivery can be markedly reduced without affecting muscle oxygen uptake in the initial phase of moderate-intensity exercise, suggesting that blood flow does not limit muscle oxygen uptake at the onset...

Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation

DEFF Research Database (Denmark)

Ramachandran, Roshni; Bhatt, Deepak Kumar; Ploug, Kenneth Beri

2014-01-01

BACKGROUND AND AIM: Infusion of glyceryltrinitrate (GTN), a nitric oxide (NO) donor, in awake, freely moving rats closely mimics a universally accepted human model of migraine and responds to sumatriptan treatment. Here we analyse the effect of nitric oxide synthase (NOS) and calcitonin gene-rela...

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine.

OpenAIRE

Galea, E; Regunathan, S; Eliopoulos, V; Feinstein, D L; Reis, D J

1996-01-01

Agmatine, decarboxylated arginine, is a metabolic product of mammalian cells. Considering the close structural similarity between L-arginine and agmatine, we investigated the interaction of agmatine and nitric oxide synthases (NOSs), which use L-arginine to generate nitric oxide (NO) and citrulline. Brain, macrophages and endothelial cells were respectively used as sources for NOS isoforms I, II and III. Enzyme activity was measured by the production of nitrites or L-citrulline. Agmatine was ...

Ultra-low power thin film transistors with gate oxide formed by nitric acid oxidation method

International Nuclear Information System (INIS)

Kobayashi, H.; Kim, W. B.; Matsumoto, T.

2011-01-01

We have developed a low temperature fabrication method of SiO 2 /Si structure by use of nitric acid, i.e., nitric acid oxidation of Si (NAOS) method, and applied it to thin film transistors (TFT). A silicon dioxide (SiO 2 ) layer formed by the NAOS method at room temperature possesses 1.8 nm thickness, and its leakage current density is as low as that of thermally grown SiO 2 layer with the same thickness formed at ∼900 deg C. The fabricated TFTs possess an ultra-thin NAOS SiO 2 /CVD SiO 2 stack gate dielectric structure. The ultrathin NAOS SiO 2 layer effectively blocks a gate leakage current, and thus, the thickness of the gate oxide layer can be decreased from 80 to 20 nm. The thin gate oxide layer enables to decrease the operation voltage to 2 V (cf. the conventional operation voltage of TFTs with 80 nm gate oxide: 12 V) because of the low threshold voltages, i.e., -0.5 V for P-ch TFTs and 0.5 V for N-ch TFTs, and thus the consumed power decreases to 1/36 of that of the conventional TFTs. The drain current increases rapidly with the gate voltage, and the sub-threshold voltage is ∼80 mV/dec. The low sub-threshold swing is attributable to the thin gate oxide thickness and low interface state density of the NAOS SiO 2 layer. (authors)

The effect of energetic electron precipitation on the nitric oxide density in the lower thermosphere

International Nuclear Information System (INIS)

Saetre, Camilla

2006-12-01

The objective of this thesis has been the study of the chemical effects of the electron precipitation in the upper atmosphere, and mainly the increase of thermospheric nitric oxide (NO). NO plays an important role in the temperature balance for the mesosphere and thermosphere.In this project auroral electron precipitation data, derived from the Polar Ionospheric X-ray Imaging Experiment (PIXIE) and the Ultraviolet Imager (UVI) on board the Polar satellite, have been used together with NO density measurements from the Student Nitric Oxide Explorer (SNOE)

Human nitric oxide biomarker as potential NO donor in conjunction with superparamagnetic iron oxide @ gold core shell nanoparticles for cancer therapeutics.

Science.gov (United States)

Singh, Nimisha; Patel, Khushbu; Sahoo, Suban K; Kumar, Rajender

2018-03-01

Nitric oxide releasing superparamagnetic (Fe 3 O 4 -Au@NTHP) nanoparticles were synthesized by conjugation of human biomarker of nitric oxide, N-nitrosothioproline with iron oxide-gold (Fe 3 O 4 -Au) core shell nanoparticles. The structure and morphology of the prepared nanoparticles were confirmed by ATR-FTIR, HR-TEM, EDAX, XPS, DLS and VSM measurements. N-nitrosothioproline is a natural molecule and nontoxic to humans. Thus, the core shell nanoparticles prepared were highly biocompatible. The prepared Fe 3 O 4 -Au@NTHP nanoparticles also provided an excellent release of nitric oxide in dark and upon light irradiation for cancer treatment. The amount of NO release was controllable with the wavelength of light and time of irradiation. The developed nanoparticles provided efficient cellular uptake and good cytotoxicity in picomolar range when tested on HeLa cancerous cells. These nanoparticles on account of their controllable NO release can also be used to release small amount of NO for killing cancerous cells without any toxic effect. Furthermore, the magnetic and photochemical properties of these nanoparticles provides dual platform for magneto therapy and phototherapy for cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of inducible nitric oxide synthesis by azathioprine in a macrophage cell line.

Science.gov (United States)

Moeslinger, Thomas; Friedl, Roswitha; Spieckermann, Paul Gerhard

2006-06-20

Azathioprine is used as an anti-inflammatory agent. Although there are numerous data demonstrating cytotoxic and immunosuppressive properties of azathioprine and its metabolite 6-mercaptopurine, the mechanism of the anti-inflammatory action of azathioprine has not yet been fully clarified. During our study, we investigated the effects of azathioprine on the inducible nitric oxide synthase (iNOS) in lipopolysaccharide stimulated murine macrophages (RAW 264.7) by measurement of iNOS protein (immunoblotting), iNOS mRNA (semiquantitative competitive RT-PCR), and NO production (nitrite levels). Azathioprine (0-210 muM) induces a concentration dependent inhibition of inducible nitric oxide synthesis (IC50: 33.5 muM). iNOS protein expression showed a concentration dependent reduction as revealed by immunoblotting when cells were incubated with increasing amounts of azathioprine. Azathioprine decreases iNOS mRNA levels as shown by semiquantitative competitive RT-PCR. In contrast, 6-mercaptopurine showed no inhibition of inducible nitric oxide synthesis. Azathioprine did not reduce iNOS mRNA stability after the addition of actinomycin D. Enzymatic activity assays with increasing concentrations of azathioprine (0-210 muM) showed no statistically significant inhibition of iNOS enzyme activity compared to cell lysates without azathioprine. Nuclear translocation of NF-kappaB p65 subunit and binding of NF-kappaB p50 subunit from nuclear extracts to a biotinylated-consensus sequence was unaffected by azathioprine treatment. iNOS inhibition by azathioprine was associated with a decreased expression of IRF-1 (interferon regulatory factor 1) and IFN-beta (beta-interferon) mRNA. Azathioprine induced iNOS inhibition seems to be associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic anti-inflammatory agents by replacing the 6-mercaptopurine component of azathioprine with other substituents. The inhibition of

Neuronal Nitric-Oxide Synthase Deficiency Impairs the Long-Term Memory of Olfactory Fear Learning and Increases Odor Generalization

Science.gov (United States)

Pavesi, Eloisa; Heldt, Scott A.; Fletcher, Max L.

2013-01-01

Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice…

Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

Directory of Open Access Journals (Sweden)

Ketab E. Al-Otaibi

2012-01-01

Full Text Available Contrast media- (CM- induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN. Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels and myeloperoxidase (MPO and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

The Effect of Central Amygdala Nitric Oxide in Expression Of Drug Seeking Behaviors

Directory of Open Access Journals (Sweden)

Mahnaz Rahimpour

2011-11-01

Full Text Available Introduction: Previous studies shows L-arginin (nitric oxide precursor increases conditioned place preference and drug seeking behaviors whereas LG-nitro-arginine methyl ester L-NAME( as nitric oxide synthase inhibitor decreases this process. In this project, effects of intra-central amygdale bilateral injection of nitric oxide agents on drug-seeking behaviors including rearing, sniffing and compartment entrance were investigated. Method: animals were wistar male rats (200-250 g which allowed to be recovered after they’re being suffered from a surgery by strereotaxis apparatus to be cannulated in coordination of central amygdale nucleus (CeA. CPP was conducted using a five-day schedule of unbiased procedure. Findings: morphine (2.5-10 mg/kg s.c induced significant drug-seeking behaviors. Naloxone (0.1-0.4 mg/kg i.p injection pretesting (after conditioning by morphine 7.5 mg/kg decreased the expression of behaviors. When L-arginine (0.3-3 µgr/rat injected intra–CeA prior to naloxone (0.4 mg/kg, increased behaviors but L-NAME (0.3-3 µgr/rat intra–CeA injections prior to L-arginine (0.3 µgr/rat pretesting, caused significant decreasement of L-arginine response. Conclusion: NO in the CeA may play an important role in the drug seeking behaviors induced of morphine.

Inhibition of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) by Gelidium elegans Using Alternative Drying and Extraction Conditions in 3T3-L1 and RAW 264.7 Cells.

Science.gov (United States)

Jeon, Hui-Jeon; Choi, Hyeon-Son; Lee, Ok-Hwan; Jeon, You-Jin; Lee, Boo-Yong

2012-06-01

Gelidium (G.) elegans is a red alga inhabiting intertidal areas of North East Asia. We examined anti-oxidative and anti-inflammatory effects of G. elegans, depending on drying and extraction conditions, by determining reactive oxygen species (ROS) and nitric oxide (NO) in 3T3-L1 and RAW 264.7 cells. Extraction yields of samples using hot air drying (HD) and far-infrared ray drying (FID) were significantly higher than those using natural air drying (ND). The 70% ethanol extracts showed the highest total phenol and flavonoid contents compared to other extracts (0, 30, and 50% ethanol) under tested drying conditions. The scavenging activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitrite correlated with total phenol or flavonoid content in the extracts. The greatest DPPH scavenging effect was observed in 70% ethanol extract from FID and HD conditions. The production of ROS and NO in 3T3-L1 and macrophage cells greatly decreased with the 70% ethanol extraction derived from FID. This study suggests that 70% ethanol extraction of G. elegans dried by FID is the most optimal condition to obtain efficiently antioxidant compounds of G. elegans.

Nitric oxide signaling pathways involved in the inhibition of spontaneous activity in the guinea pig prostate.

Science.gov (United States)

Dey, Anupa; Lang, Richard J; Exintaris, Betty

2012-06-01

We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates. Conventional intracellular microelectrode and tension recording techniques were used. The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA pguinea pig prostates (Student paired t test pproduction. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Arginase expression modulates nitric oxide production in Leishmania (Leishmania) amazonensis.

Science.gov (United States)

Acuña, Stephanie Maia; Aoki, Juliana Ide; Laranjeira-Silva, Maria Fernanda; Zampieri, Ricardo Andrade; Fernandes, Juliane Cristina Ribeiro; Muxel, Sandra Marcia; Floeter-Winter, Lucile Maria

2017-01-01

Arginase is an enzyme that converts L-arginine to urea and L-ornithine, an essential substrate for the polyamine pathway supporting Leishmania (Leishmania) amazonensis replication and its survival in the mammalian host. L-arginine is also the substrate of macrophage nitric oxide synthase 2 (NOS2) to produce nitric oxide (NO) that kills the parasite. This competition can define the fate of Leishmania infection. The transcriptomic profiling identified a family of oxidoreductases in L. (L.) amazonensis wild-type (La-WT) and L. (L.) amazonensis arginase knockout (La-arg-) promastigotes and axenic amastigotes. We highlighted the identification of an oxidoreductase that could act as nitric oxide synthase-like (NOS-like), due to the following evidences: conserved domain composition, the participation of NO production during the time course of promastigotes growth and during the axenic amastigotes differentiation, regulation dependence on arginase activity, as well as reduction of NO amount through the NOS activity inhibition. NO quantification was measured by DAF-FM labeling analysis in a flow cytometry. We described an arginase-dependent NOS-like activity in L. (L.) amazonensis and its role in the parasite growth. The increased detection of NO production in the mid-stationary and late-stationary growth phases of La-WT promastigotes could suggest that this production is an important factor to metacyclogenesis triggering. On the other hand, La-arg- showed an earlier increase in NO production compared to La-WT, suggesting that NO production can be arginase-dependent. Interestingly, La-WT and La-arg- axenic amastigotes produced higher levels of NO than those observed in promastigotes. As a conclusion, our work suggested that NOS-like is expressed in Leishmania in the stationary growth phase promastigotes and amastigotes, and could be correlated to metacyclogenesis and amastigotes growth in a dependent way to the internal pool of L-arginine and arginase activity.

Reduction Rates for Higher Americium Oxidation States in Nitric Acid

Energy Technology Data Exchange (ETDEWEB)

Grimes, Travis Shane [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mincher, Bruce Jay [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmitt, Nicholas C [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-09-30

The stability of hexavalent americium was measured using multiple americium concentrations and nitric acid concentrations after contact with the strong oxidant sodium bismuthate. Contrary to our hypotheses Am(VI) was not reduced faster at higher americium concentrations, and the reduction was only zero-order at short time scales. Attempts to model the reduction kinetics using zero order kinetic models showed Am(VI) reduction in nitric acid is more complex than the autoreduction processes reported by others in perchloric acid. The classical zero-order reduction of Am(VI) was found here only for short times on the order of a few hours. We did show that the rate of Am(V) production was less than the rate of Am(VI) reduction, indicating that some Am(VI) undergoes two electron-reduction to Am(IV). We also monitored the Am(VI) reduction in contact with the organic diluent dodecane. A direct comparison of these results with those in the absence of the organic diluent showed the reduction rates for Am(VI) were not statistically different for both systems. Additional americium oxidations conducted in the presence of Ce(IV)/Ce(III) ions showed that Am(VI) is reduced without the typical growth of Am(V) observed in the systems sans Ce ion. This was an interesting result which suggests a potential new reduction/oxidation pathway for Am in the presence of Ce; however, these results were very preliminary, and will require additional experiments to understand the mechanism by which this occurs. Overall, these studies have shown that hexavalent americium is fundamentally stable enough in nitric acid to run a separations process. However, the complicated nature of the reduction pathways based on the system components is far from being rigorously understood.

of endothelial nitric oxide synthase gene and serum level of vascular ...

African Journals Online (AJOL)

uwerhiavwe

Davignon and Ganz, 2004). NO is synthe- sized via a reaction that includes the conversion of L- arginine to L-citruline catalyzed by endothelial nitric oxide synthase (eNOS), which is one of the three isoforms of the enzyme (Mayer and Hemmens, 1997) ...

Study of Oxidizing Agents for Tritium Removal in ITER -Compatible Conditions: Alternatives to Oxygen and Ozone

International Nuclear Information System (INIS)

Tabares, F. L.; Tafalla, D.; Ferreira, J. A.; Gomez-Aleixandre, C.; Maria Albella, J.; Soria, J.; Rodriguez-Ramos, I.

2007-01-01

In the present report, the studies of tritiated carbon-film removal by oxidizing agents other than Oxygen and Ozone in ITER are described. Exposure of laboratory produced a-C:H/D films and tokamak flakes (Asdex Upgrade and Textor) to nitric oxide, water and hydrogen peroxide has been carried out. Temperatures of exposure up to 350 degree centigree were used, and thermal desorption of the samples at temperatures up to 750 degree centigree was performed for sample characterization prior to and after the treatment. Elastic Recoil Detection Analysis (ERDA), Infrared Spectroscopy, XPS and Nano indentation hardness analysis were applied to the characterization of the physical and chemical changes of the samples. This work was done under the EFDA Task 04-1175. (Author) 8 refs

Study of Oxidizing Agents for Tritium Removal in ITER -Compatible Conditions: Alternatives to Oxygen and Ozone

Energy Technology Data Exchange (ETDEWEB)

Tabares, F. L.; Tafalla, D.; Ferreira, J. A.; Gomez-Aleixandre, C.; Maria Albella, J.; Soria, J.; Rodriguez-Ramos, I.

2007-07-20

In the present report, the studies of tritiated carbon-film removal by oxidizing agents other than Oxygen and Ozone in ITER are described. Exposure of laboratory produced a-C:H/D films and tokamak flakes (Asdex Upgrade and Textor) to nitric oxide, water and hydrogen peroxide has been carried out. Temperatures of exposure up to 350 degree centigree were used, and thermal desorption of the samples at temperatures up to 750 degree centigree was performed for sample characterization prior to and after the treatment. Elastic Recoil Detection Analysis (ERDA), Infrared Spectroscopy, XPS and Nano indentation hardness analysis were applied to the characterization of the physical and chemical changes of the samples. This work was done under the EFDA Task 04-1175. (Author) 8 refs.

Nitric oxide and plant iron homeostasis.

Science.gov (United States)

Buet, Agustina; Simontacchi, Marcela

2015-03-01

Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. © 2015 New York Academy of Sciences.

Prenatal irradiation: nitric oxide and oxidative stress roles in radiation-induced apoptosis of the developing central nervous system

International Nuclear Information System (INIS)

Sanjurjo, Julieta

2001-01-01

. Apoptosis was measured by flow cytometry. Cellular response to radiation injury was clearly dependent on the dose, with a significant increase in apoptosis death from 0,4 Gy on, measured 20 hours post irradiation and increasing in a linear way with total dose. Furthermore, apoptosis of cortical cells was dependant on developmental age. That is, it depends on both the proliferation rate and the differentiation stage, being maximal at day 15 of gestational age and decreasing to day 19. The time-course evolution of apoptosis revealed a significant increase from 4 hours post irradiation for a 2 Gy fixed dose, showing that though it is an early event, it continues to happen with an augmentation of apoptotic cells number to 20 hours post irradiation. Several mechanisms have been proposed for the etiology of neuronal apoptosis. Nitric oxide (NO) production and oxidative stress have been implicated in the neuronal injury seen in different neuro degenerative disorders. It is well-known that the excessive stimulation of glutamate receptors could mediate neuronal death by NO and superoxide anion, whose combination form peroxynitrite, a potent neurotoxic molecule. In spite of that, cortical cultures treatment with nitric oxide synthase (NOS) inhibitors, L-NAME and N-Arginine and with NMDA receptor antagonist MK801 produced a statistically significant increase of radiation-induced apoptosis at every concentration and incubation times tested. Because of this, NMDA receptors blockade could be implicated in NOS activity reduction and thus, in a minor NO production rate. Nitric oxide could be playing a protective role in this system. In some cases NO could potentate Reactive Oxygen Species (ROS) toxicity, but in other circumstances it could have direct or indirect antioxidant actions in biologic systems subjected to oxidative stress due to excessive ROS production, mainly protecting biologic membranes from lipid peroxidation. Besides NO actions, it is evident that radiation

Investigation of ferromagnetism in oxygen deficient hafnium oxide thin films

Energy Technology Data Exchange (ETDEWEB)

Hildebrandt, Erwin; Kurian, Jose; Krockenberger, Yoshiharu; Alff, Lambert [Institut fuer Materialwissenschaft, TU Darmstadt (Germany); Suter, Andreas [PSI, Villingen (Switzerland); Wilhelm, Fabrice; Rogalev, Andrei [ESRF, Grenoble (France)

2008-07-01

Oxygen deficient thin films of hafnium oxide were grown on single crystal r-cut and c-cut sapphire by reactive molecular beam epitaxy. RF-activated oxygen was used for the in situ oxidation of hafnium oxide thin films. Oxidation conditions were varied substantially in order to create oxygen deficiency in hafnium oxide films intentionally. The films were characterized by X-ray and magnetic measurements. X-ray diffraction studies show an increase in lattice parameter with increasing oxygen deficiency. Oxygen deficient hafnium oxide thin films also showed a decreasing bandgap with increase in oxygen deficiency. The magnetisation studies carried out with SQUID did not show any sign of ferromagnetism in the whole oxygen deficiency range. X-ray magnetic circular dichroism measurements also confirmed the absence of ferromagnetism in oxygen deficient hafnium oxide thin films.

The role of nitric oxide radicals in removal of hyper-radiosensitivity by priming irradiation

International Nuclear Information System (INIS)

Edin, Nina Jeppesen; Sandvik, Joe Alexander; Pettersen, Erik Olai; Vollan, Hilde Synnove; Reger, Katharina; Görlach, Agnes

2013-01-01

In this study, a mechanism in which low-dose hyper-radiosensitivity (HRS) is permanently removed, induced by low-dose-rate (LDR) (0.2 - 0.3 Gy/h for 1 h) but not by high-dose-rate priming (0.3 Gy at 40 Gy/h) was investigated. One HRS-negative cell line (NHIK 3025) and two HRS-positive cell lines (T-47D, T98G) were used. The effects of different pretreatments on HRS were investigated using the colony assay. Cell-based ELISA was used to measure nitric oxide synthase (NOS) levels, and microarray analysis to compare gene expression in primed and unprimed cells. The data show how permanent removal of HRS, previously found to be induced by LDR priming irradiation, can also be induced by addition of nitric oxide (NO)-donor DEANO combined with either high-dose-rate priming or exposure to prolonged cycling hypoxia followed by reoxygenation, a treatment not involving radiation. The removal of HRS appears not to involve DNA damage induced during priming irradiation as it was also induced by LDR irradiation of cell-conditioned medium without cells present. The permanent removal of HRS in LDR-primed cells was reversed by treatment with inducible nitric oxide synthase (iNOS) inhibitor 1400W. Furthermore, 1400W could also induce HRS in an HRS-negative cell line. The data suggest that LDR irradiation for 1 h, but not 15 min, activates iNOS, and also that sustained iNOS activation is necessary for the permanent removal of HRS by LDR priming. The data indicate that nitric oxide production is involved in the regulatory processes determining cellular responses to low-dose-rate irradiation. (author)

JS-K, a Nitric Oxide Prodrug, Has Enhanced Cytotoxicity in Colon Cancer Cells with Knockdown of Thioredoxin Reductase 1

Science.gov (United States)

Edes, Kornelia; Cassidy, Pamela; Shami, Paul J.; Moos, Philip J.

2010-01-01

Background The selenoenzyme thioredoxin reductase 1 has a complex role relating to cell growth. It is induced as a component of the cellular response to potentially mutagenic oxidants, but also appears to provide growth advantages to transformed cells by inhibiting apoptosis. In addition, selenocysteine-deficient or alkylated forms of thioredoxin reductase 1 have also demonstrated oxidative, pro-apoptotic activity. Therefore, a greater understanding of the role of thioredoxin reductase in redox initiated apoptotic processes is warranted. Methodology The role of thioredoxin reductase 1 in RKO cells was evaluated by attenuating endogenous thioredoxin reductase 1 expression with siRNA and then either inducing a selenium-deficient thioredoxin reductase or treatment with distinct redox challenges including, hydrogen peroxide, an oxidized lipid, 4-hydroxy-2-nonenol, and a nitric oxide donating prodrug. Thioredoxin redox status, cellular viability, and effector caspase activity were measured. Conclusions/Significance In cells with attenuated endogenous thioredoxin reductase 1, a stably integrated selenocysteine-deficient form of the enzyme was induced but did not alter either the thioredoxin redox status or the cellular growth kinetics. The oxidized lipid and the nitric oxide donor demonstrated enhanced cytotoxicity when thioredoxin reductase 1 was knocked-down; however, the effect was more pronounced with the nitric oxide prodrug. These results are consistent with the hypothesis that attenuation of the thioredoxin-system can promote apoptosis in a nitric oxide-dependent manner. PMID:20098717

Constitutive nitric oxide synthase (cNOS activity in Langerhans islets from streptozotocin diabetic rats

Directory of Open Access Journals (Sweden)

Fonovich de Schroeder T.M.

1998-01-01

Full Text Available Nitric oxide synthase activity was measured in Langerhans islets isolated from control and streptozotocin diabetic rats. The activity of the enzyme was linear up to 150 µg of protein from control rats and was optimal at 0.1 µM calcium, when it was measured after 45 min of incubation at 37oC in the presence of 200 µM arginine. Specific activity of the enzyme was 25 x 10-4 nmol [3H]citrulline 45 min-1 mg protein-1. Streptozotocin diabetic rats exhibited less enzyme activity both in total pancreas homogenate and in isolated Langerhans islets when compared to control animals. Nitric oxide synthase activity measured in control and diabetic rats 15 days after the last streptozotocin injection in the second group of animals corresponded only to a constitutive enzyme since it was not inhibited by aminoguanidine in any of the mentioned groups. Hyperglycemia in diabetic rats may be the consequence of impaired insulin release caused at least in part by reduced positive modulation mediated by constitutive nitric oxide synthase activity, which was dramatically reduced in islets severely damaged after streptozotocin treatment.

Feline Toxoplasmosis: Tumor Necrosis Factor, Nitric Oxide, and Free Radicals in Seropositive Cats.

Science.gov (United States)

Faria, Joice L M; Couto, Caroline do; Wierzynski, Sheron L; Bottari, Nathieli B; Baldissera, Matheus D; Pereira, Wanderson A B; Da Silva, Aleksandro S

2018-02-01

Toxoplasma gondii is a cosmopolitan protozoan that causes disease in several species, including humans. In cats, these infections are usually asymptomatic, but in other species they can lead to high levels of inflammatory and cell damage markers, causing cellular damage. Therefore, the aim of this study was to measure levels of tumor necrosis factor (TNF-α), reactive oxygen species (ROS), and nitric oxide (nitrite/nitrate-NO x ) in the serum of cats seropositive for T. gondii. Initially, we investigated the presence of antibodies against T. gondii in cats in the city of Concordia, Santa Catarina, Brazil, with the use of indirect immunofluorescence (IFA), and found 30 cats seropositive for T. gondii and 30 seronegative cats. In this study, seropositive cats showed higher levels of TNF-α, ROS, and NO x compared to seronegative cats. Although cats do not show clinical signs of disease, constant inflammatory response can cause cell damage, which over time may adversely affect the animal.

Oxygen Storage Capacity and Oxygen Mobility of Co-Mn-Mg-Al Mixed Oxides and Their Relation in the VOC Oxidation Reaction

Directory of Open Access Journals (Sweden)

María Haidy Castaño

2015-05-01

Full Text Available Co-Mn-Mg-Al oxides were synthesized using auto-combustion and co-precipitation techniques. Constant ratios were maintained with (Co + Mn + Mg/Al equal to 3.0, (Co + Mn/Mg equal to 1.0 and Co/Mn equal to 0.5. The chemical and structural composition, redox properties, oxygen storage capacity and oxygen mobility were analyzed using X-ray fluorescence (XRF, X-ray diffraction (XRD, Raman spectroscopy, scanning electron microscopy (SEM, temperature-programmed reduction of hydrogen (H2-TPR, oxygen storage capacity (OSC, oxygen storage complete capacity (OSCC and isotopic exchange, respectively. The catalytic behavior of the oxides was evaluated in the total oxidation of a mixture of 250 ppm toluene and 250 ppm 2-propanol. The synthesis methodology affected the crystallite size, redox properties, OSC and oxide oxygen mobility, which determined the catalytic behavior. The co-precipitation method got the most active oxide in the oxidation of the volatile organic compound (VOC mixture because of the improved mobility of oxygen and ability to favor redox processes in the material structure.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

Science.gov (United States)

Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

2017-06-01

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

Involvement of the nitric oxide in melatonin-mediated protection against injury.

Science.gov (United States)

Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

2018-05-01

Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-Biofilm Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

OpenAIRE

Hetrick, Evan M.; Shin, Jae Ho; Paul, Heather S.; Schoenfisch, Mark H.

2009-01-01

The ability of nitric oxide (NO)-releasing silica nanoparticles to kill biofilm-based microbial cells is reported. Biofilms of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were formed in vitro and exposed to NO-releasing silica nanoparticles. Replicative viability experiments revealed that ≥ 99% of cells from each type of biofilm were killed via NO release, with the greatest efficacy (≥ 99.999% killing) against gram-negative...

Geomagnetic control of mesospheric nitric oxide concentration from simultaneous D and F region ionization measurements

International Nuclear Information System (INIS)

Pradhan, S.N.; Shirke, J.S.

1978-01-01

Investigations are made of D-region electron density profiles derived from 'partial reflection' measurements over a low latitude station (Ahmedabad) during a year of low solar activity. The index relating the electron density with the solar zenith angle is found to increase towards lower zenith angles suggesting both diurnal and seasonal variations in the Nitric oxide concentration. A close correlation is also found between the electron density at 80 km and the maximum ionization density in the F region above. This is interpreted as due to concomitant variation of a sizeable fraction of the Nitric oxide concentration in the mesosphere and lower thermosphere with the overhead F region ionization. A simplified global model is presented for the mesospheric Nitric oxide concentration based on the morphological features of F region and the relationship existing between the ionization levels in F and D regions. Many observed features of the D region ionization including the solar zenith angle dependence, latitudinal and geomagnetic anomaly and long term variability are explained on the basis of this model

Investigations on the oxidation of nitric acid plutonium solutions with ozone

International Nuclear Information System (INIS)

Boehm, M.

1983-01-01

The reaction of ozone with nitric acid Pu solutions was studied as a function of reaction time, acid concentration and Pu concentration. Strong nitric acid Pu solutions are important in nuclear fuel element production and reprocessing. The Pu must be converted into hexavalent Pu before precipitation from the homogeneous solution together with uranium-IV, ammonia and CO 2 in the form of ammonium uranyl/plutonyl carbonate (AUPuC). Formation of a solid phase during ozonation was observed for the first time. The proneness to solidification increases with incrasing plutonium concentrations and with decreasing acid concentrations. If the formation of a solid phase during ozonation of nitric acid Pu solutions cannot be prevented, the PU-IV oxidation process described is unsuitable for industrial purposes as Pu solutions in industrial processes have much higher concentrations than the solutions used in the present investigation. (orig./EF) [de

Absorption and oxidation of nitrogen oxide in ionic liquids

DEFF Research Database (Denmark)

Kunov-Kruse, Andreas Jonas; Thomassen, Peter Langelund; Riisager, Anders

2016-01-01

A new strategy for capturing nitrogen oxide, NO, from the gas phase is presented. Dilute NO gas is removed from the gas phase by ionic liquids under ambient conditions. The nitrate anion of the ionic liquid catalyzes the oxidation of NO to nitric acid by atmospheric oxygen in the presence of water....... The nitric acid is absorbed in the ionic liquid up to approximately one mole HNO3 per mole of the ionic liquid due to the formation of hydrogen bonds. The nitric acid can be desorbed by heating, thereby regenerating the ionic liquid with excellent reproducibility. Here, time-resolved in-situ spectroscopic...... investigations of the reaction and products are presented. The procedure reveals a new vision for removing the pollutant NO by absorption into a non-volatile liquid and converting it into a useful bulk chemical, that is, HNO3....

Nitric oxide in plants: an assessment of the current state of knowledge

DEFF Research Database (Denmark)

Mur, Luis A J; Mandon, Julien; Persijn, Stefan

2013-01-01

Background and aims After a series of seminal works during the last decade of the 20th century nitric oxide (NO) is now firmly placed in the pantheon of plant signals. NO acts in plant-microbe interactions, responses to abiotic stress, stomatal regulation and a range of developmental processes...... of NO production from DEANO (diethylamine nitric oxide), S-nitrosoglutathione (GSNO) and sodium nitroprusside (SNP) following infiltration of tobacco leaves which could aid workers in their experiments. Further, based on current data it is difficult to define a bespoke plant NO signalling pathway, but rather....... By considering the recent advances in plant NO biology, this review will highlight certain key aspects that require further attention. Scope and conclusions The following questions will be considered. Whilst cytosolic nitrate reductase is an important source of NO, the contributions of other mechanisms...

Expression of inducible nitric oxide synthase in trigeminal ganglion cells during culture

DEFF Research Database (Denmark)

Jansen-Olesen, Inger; Zhou, MingFang; Zinck, Tina Jovanovic

2005-01-01

RNA and protein could be detected. The data suggest that iNOS expression may be a molecular mechanism mediating the adaptive response of trigeminal ganglia cells to the serum free stressful stimulus the culture environment provides. It may act as a cellular signalling molecule that is expressed after cell......Nitric oxide (NO) is an important signalling molecule that has been suggested to be a key molecule for induction and maintenance of migraine attacks based on clinical studies, animal experimental studies and the expression of nitric oxide synthase (NOS) immunoreactivity within the trigeminovascular......, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. In trigeminal ganglia cells not subjected to culture, endothelial (e) and neuronal (n) but not inducible (i) NOS mRNA and protein were detected. Culture of rat neurones resulted in a rapid axonal outgrowth of NOS positive...

The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

Science.gov (United States)

Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

2008-10-01

To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse

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Sophie A. Bradley

2016-01-01

Full Text Available Nitric oxide (NO is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS, new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s.

Exhaled nitric oxide in stable chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Beg Mohammed F S; Alzoghaibi, Mohammad A; Habib, Syed S; Abba, Abdullah A

2009-01-01

The objective of the study was to test the hypothesis that fraction of exhaled nitric oxide (FENO) is elevated in nonsmoking subjects with stable chronic obstructive pulmonary disease (COPD) and compare it with the results in patients with asthma and a control population. Pulmonology Clinic at a University Hospital. Twenty five control subjects, 25 steroid naive asthmatics and 14 COPD patients were studied. All the patients were nonsmokers and stable at the time of the study. All subjects completed a questionnaire and underwent spirometry. Exhaled nitric oxide was measured online by chemiluminescence, using single-breath technique. All the study subjects were males. Subjects with stable COPD had significantly higher values of FENO than controls (56.54+ - 28.01 vs 22.00 + -6.69; P =0.0001) but lower than the subjects with asthma (56.54+ - 28.01 vs 84.78+ - 39.32 P 0.0285). The FENO values in COPD subjects were inversely related to the FEV 1 /FVC ratio. There was a significant overlap between the FENO values in COPD and the control subjects. There is a significant elevation in FENO in patients with stable COPD, but the elevation is less than in asthmatic subjects. Its value in clinical practice may be limited by the significant overlap with control subjects. (author)

Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK.

Science.gov (United States)

Merry, Troy L; Steinberg, Gregory R; Lynch, Gordon S; McConell, Glenn K

2010-03-01

Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPKalpha2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-l-cysteine (NAC) or the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). Contraction increased AMPKalpha2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and l-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and l-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPKalpha Thr(172) phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or l-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism.

Nitric oxide production by necrotrophic pathogen Macrophomina phaseolina and the host plant in charcoal rot disease of jute: complexity of the interplay between necrotroph-host plant interactions.

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Tuhin Subhra Sarkar

Full Text Available M. phaseolina, a global devastating necrotrophic fungal pathogen causes charcoal rot disease in more than 500 host plants. With the aim of understanding the plant-necrotrophic pathogen interaction associated with charcoal rot disease of jute, biochemical approach was attempted to study cellular nitric oxide production under diseased condition. This is the first report on M. phaseolina infection in Corchorus capsularis (jute plants which resulted in elevated nitric oxide, reactive nitrogen species and S nitrosothiols production in infected tissues. Time dependent nitric oxide production was also assessed with 4-Amino-5-Methylamino-2',7'-Difluorofluorescein Diacetate using single leaf experiment both in presence of M. phaseolina and xylanases obtained from fungal secretome. Cellular redox status and redox active enzymes were also assessed during plant fungal interaction. Interestingly, M. phaseolina was found to produce nitric oxide which was detected in vitro inside the mycelium and in the surrounding medium. Addition of mammalian nitric oxide synthase inhibitor could block the nitric oxide production in M. phaseolina. Bioinformatics analysis revealed nitric oxide synthase like sequence with conserved amino acid sequences in M. phaseolina genome sequence. In conclusion, the production of nitric oxide and reactive nitrogen species may have important physiological significance in necrotrophic host pathogen interaction.

Nitric oxide in a diesel engine : laser-based detection and interpretation

NARCIS (Netherlands)

Stoffels, G.G.M.

1999-01-01

Nitric oxide (NO) is one of the most polluting components in the exhaust gases of a diesel engines. Therefore, knowledge of the time and place where it is produced during the combustion process is of interest to find a way to reduce diesel engine emissions. Non-intrusive optical diagnostics, based

Native Alanine Substitution in the Glycine Hinge Modulates Conformational Flexibility of Heme Nitric Oxide/Oxygen (H-NOX) Sensing Proteins.

Science.gov (United States)

Hespen, Charles W; Bruegger, Joel J; Guo, Yirui; Marletta, Michael A

2018-06-15

Heme nitric oxide/oxygen sensing (H-NOX) domains are direct NO sensors that regulate a variety of biological functions in both bacteria and eukaryotes. Previous work on H-NOX proteins has shown that upon NO binding, a conformational change occurs along two glycine residues on adjacent helices (termed the glycine hinge). Despite the apparent importance of the glycine hinge, it is not fully conserved in all H-NOX domains. Several H-NOX sensors from the family Flavobacteriaceae contain a native alanine substitution in one of the hinge residues. In this work, the effect of the increased steric bulk within the Ala-Gly hinge on H-NOX function was investigated. The hinge in Kordia algicida OT-1 ( Ka H-NOX) is composed of A71 and G145. Ligand-binding properties and signaling function for this H-NOX were characterized. The variant A71G was designed to convert the hinge region of Ka H-NOX to the typical Gly-Gly motif. In activity assays with its cognate histidine kinase (HnoK), the wild type displayed increased signal specificity compared to A71G. Increasing titrations of unliganded A71G gradually inhibits HnoK autophosphorylation, while increasing titrations of unliganded wild type H-NOX does not inhibit HnoK. Crystal structures of both wild type and A71G Ka H-NOX were solved to 1.9 and 1.6 Å, respectively. Regions of H-NOX domains previously identified as involved in protein-protein interactions with HnoK display significantly higher b-factors in A71G compared to wild-type H-NOX. Both biochemical and structural data indicate that the hinge region controls overall conformational flexibility of the H-NOX, affecting NO complex formation and regulation of its HnoK.

The effects of oxygen on process rates and gene expression of anammox and denitrification in the Eastern South Pacific oxygen minimum zone

DEFF Research Database (Denmark)

Dalsgaard, Tage; Stewart, Frank; De Brabandere, Loreto

Oxygen concentrations were consistently below our detection limit of 90 nM for a distance of > 2000 km in the oxygen minimum zone (OMZ) along the coasts of Chile and Peru. In most cases, anammox and denitrification were only detected when in situ oxygen concentrations were below detection...... differently to oxygen. When normalized to a housekeeping gene (rpoB), the expression of 4 out of 9 N-cycle-genes changed with increasing oxygen concentration: The expression of ammonium monooxygenase (amoC) was stimulated, whereas expression of nitrite reductase (nirS), nitric oxide reductase (nor...

Role of nitric oxide in cellular iron metabolism.

Science.gov (United States)

Kim, Sangwon; Ponka, Prem

2003-03-01

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

Protective effect of nitric oxide against arsenic-induced oxidative ...

African Journals Online (AJOL)

The effects of NO on alleviating arsenic-induced oxidative damage in tall fescue leaves were investigated. Arsenic (25 M) treatment induced significantly accumulation of reactive oxygen species (ROS) and led to serious lipid peroxidation in tall fescue leaves and the application of 100 M SNP before arsenic stress resulted ...

Role of Reactive Oxygen Species and Nitric Oxide in Mediating Chemotherapeutic Drug Induced Bystander Response in Human Cancer Cells Exposed In-Vitro

Science.gov (United States)

Chinnadurai, Mani; Rao, Bhavna S; Deepika, Ramasamy; Paul, Solomon F.D.; Venkatachalam, Perumal

2012-01-01

Background The intention of cancer chemotherapy is to control the growth of cancer cells using chemical agents. However, the occurrence of second malignancies has raised concerns, leading to re-evaluation of the current strategy in use for chemotherapeutic agents. Although the mechanisms involved in second malignancy remain ambiguous, therapeutic-agent-induced non-DNA targeted effects like bystander response and genomic instability cannot be eliminated completely. Hence, Bleomycin (BLM) and Neocarzinostatin (NCS), chemotherapeutic drugs with a mode of action similar to ionizing radiation, were used to study the mechanism of bystander response in human cancer cells (A549, CCRF-CEM and HL-60) by employing co-culture methodology. Methods Bystander effect was quantified using micronucleus (MN) assay and in-situ immunofluorescence(γH2AX assay).The role of reactive oxygen species (ROS) and nitric oxide (NO) in mediating the bystander response was explored by pre-treating bystander cells with dimethylsulphoxide (DMSO) and C-PTIO respectively. Results Bystander response was observed only in CCRF-CEM and A549 cells (P bystander response on treatment with DMSO, suggests that ROS has a more significant role in mediating the bystander response.Since the possibility of the ROS and NO in mediating these bystander effect was confirmed, mechanistic control of these signaling molecules could either reduce radiation damage and potential carcinogenicity of normal tissues (by reducing bystander signaling) or maximize cell sterilization during chemotherapy (by amplifying bystander responses in tumors). PMID:29147282

Simulation of nitrous oxide and nitric oxide emissions from tropical primary forests in the Costa Rican Atlantic Zone

Science.gov (United States)

Shuguanga Liu; William A. Reiners; Michael Keller; Davis S. Schimel

2000-01-01

Nitrous oxide (N2O) and nitric oxide (NO) are important atmospheric trace gases participating in the regulation of global climate and environment. Predictive models on the emissions of N2O and NO emissions from soil into the atmosphere are required. We modified the CENTURY model (Soil Sci. Soc. Am. J., 51 (1987) 1173) to simulate the emissions of N2O and NO from...

Mid-Ir Cavity Ring-Down Spectrometer for Biological Trace Nitric Oxide Detection

Science.gov (United States)

Kan, Vincent; Ragab, Ahemd; Stsiapura, Vitali; Lehmann, Kevin K.; Gaston, Benjamin M.

2011-06-01

S-nitrosothiols have received much attention in biochemistry and medicine as donors of nitrosonium ion (NO^+) and nitric oxide (NO) - physiologically active molecules involved in vasodilation and signal transduction. Determination of S-nitrosothiols content in cells and tissues is of great importance for fundamental research and medical applications. We will report on our ongoing development of a instrument to measure trace levels of nitric oxide gas (NO), released from S-nitrosothiols after exposure to UV light (340 nm) or reaction with L-Cysteine+CuCl mixture. The instrument uses the method of cavity ring-down spectroscopy, probing rotationally resolved lines in the vibrational fundamental transition near 5.2 μm. The laser source is a continuous-wave, room temperature external cavity quantum cascade laser. An acousto-optic modulator is used to abruptly turn off the optical power incident on the cavity when the laser and cavity pass through resonance.

Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity

International Nuclear Information System (INIS)

Wu Defeng; Cederbaum, Arthur

2006-01-01

Polyunsaturated fatty acids such as arachidonic acid (AA) play an important role in alcohol-induced liver injury. AA promotes toxicity in rat hepatocytes with high levels of cytochrome P4502E1 and in HepG2 E47 cells which express CYP2E1. Nitric oxide (NO) participates in the regulation of various cell activities as well as in cytotoxic events. NO may act as a protectant against cytotoxic stress or may enhance cytotoxicity when produced at elevated concentrations. The goal of the current study was to evaluate the effect of endogenously or exogenously produced NO on AA toxicity in liver cells with high expression of CYP2E1 and assess possible mechanisms for its actions. Pyrazole-induced rat hepatocytes or HepG2 cells expressing CYP2E1 were treated with AA in the presence or absence of an inhibitor of nitric oxide synthase L-N G -Nitroarginine Methylester (L-NAME) or the NO donors S-nitroso-N-acetylpenicillamine (SNAP), and (Z)-1-[-(2-aminoethyl)-N-(2-aminoethyl)]diazen-1-ium-1,2-diolate (DETA-NONO). AA decreased cell viability from 100% to 48 ± 6% after treatment for 48 h. In the presence of L-NAME, viability was further lowered to 23 ± 5%, while, SNAP or DETA-NONO increased viability to 66 ± 8 or 71 ± 6%. The L-NAME potentiated toxicity was primarily necrotic in nature. L-NAME did not affect CYP2E1 activity or CYP2E1 content. SNAP significantly lowered CYP2E1 activity but not protein. AA treatment increased lipid peroxidation and lowered GSH levels. L-NAME potentiated while SNAP prevented these changes. Thus, L-NAME increased, while NO donors decreased AA-induced oxidative stress. Antioxidants prevented the L-NAME potentiation of AA toxicity. Damage to mitochondria by AA was shown by a decline in the mitochondrial membrane potential (MMP). L-NAME potentiated this decline in MMP in association with its increase in AA-induced oxidative stress and toxicity. NO donors decreased this decline in MMP in association with their decrease in AA-induced oxidative stress and

NITRIC OXIDE ACTIVITY OF NEUTROPHIL IN BLOOD AND CEREBROSPINAL FLUID OF THE CHILDREN WITH BACTERIAL AND VIRAL MENINGITIS

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V. P. Molochniy

2014-01-01

Full Text Available The article presents the results of study of nitric oxide activity of neutrophil leucocytic and freeradical processes in blood and cerebrospinal fluid of the children with bacterial and viral meningitison the acute period diseases. The peculiarities or activity of freeradical processes and nitric oxide of cerebrospinal fluid with bacterial meningitis in acute period diseases and activities of studies of ferments with the health children. 

Exhaled nitric oxide in diagnosis and management of respiratory diseases

Directory of Open Access Journals (Sweden)

Abba Abdullah

2009-01-01

Full Text Available The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases.