scholarly journals Nitric oxide and oxidative stress (H2O2) control mammalian iron metabolism by different pathways.

1996 ◽  
Vol 16 (7) ◽  
pp. 3781-3788 ◽  
Author(s):  
K Pantopoulos ◽  
G Weiss ◽  
M W Hentze
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
De Novo ◽  
Reactive Oxygen ◽  
Target Cells ◽  
Induction Phase ◽  
Reactive Oxygen Intermediate ◽  
Oxygen Intermediates

Several cellular mRNAs are regulated posttranscriptionally by iron-responsive elements (IREs) and the cytosolic IRE-binding proteins IRP-1 and IRP-2. Three different signals are known to elicit IRP-1 activity and thus regulate IRE-containing mRNAs: iron deficiency, nitric oxide (NO), and the reactive oxygen intermediate hydrogen peroxide (H2O2). In this report, we characterize the pathways for IRP-1 regulation by NO and H2O2 and examine their effects on IRP-2. We show that the responses of IRP-1 and IRP-2 to NO remarkably resemble those elicited by iron deficiency: IRP-1 induction by NO and by iron deficiency is slow and posttranslational, while IRP-2 induction by these inductive signals is slow and requires de novo protein synthesis. In contrast, H2O2 induces a rapid posttranslational activation which is limited to IRP-1. Removal of the inductive signal H2O2 after < or = 15 min of treatment (induction phase) permits a complete IRP-1 activation within 60 min (execution phase) which is sustained for several hours. This contrasts with the IRP-1 activation pathway by NO and iron depletion, in which NO-releasing drugs or iron chelators need to be present during the entire activation phase. Finally, we demonstrate that biologically synthesized NO regulates the expression of IRE-containing mRNAs in target cells by passive diffusion and that oxidative stress endogenously generated by pharmacological modulation of the mitochondrial respiratory chain activates IRP-1, underscoring the physiological significance of NO and reactive oxygen intermediates as regulators of cellular iron metabolism. We discuss models to explain the activation pathways of IRP-1 and IRP-2. In particular, we suggest the possibility that NO affects iron availability rather than the iron-sulfur cluster of IRP-1.

scholarly journals The role of oxidative/nitrosative stress in pathogenesis of paracetamol-induced toxic hepatitis

2010 ◽  
Vol 63 (11-12) ◽  
pp. 827-832 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Dusan Mladenovic ◽  
Danijela Vucevic ◽  
Rada Jesic-Vukicevic
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Severe Liver ◽  
Hepatocellular Necrosis

Introduction. Paracetamol is an effective analgesic/antipyretic drug when used at therapeutic doses. However, the overdose of paracetamol can cause severe liver injury and liver necrosis. The mechanism of paracetamol-induced liver injury is still not completely understood. Reactive metabolite formation, depletion of glutathione and alkylation of proteins are the triggers of inhibition of mitochondrial respiration, adenosine triphosphate depletion and mitochondrial oxidant stress leading to hepatocellular necrosis. Role of oxidative stress in paracetamol-induced liver injury. The importance of oxidative stress in paracetamol hepatotoxicity is controversial. Paracetamol induced liver injury cause the formation of reactive oxygen species. The potent sources of reactive oxygen are mitochondria, neutrophils, Kupffer cells and the enzyme xatnine oxidase. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in paracetamol-induced oxidative stress. The production of mitochondrial reactive oxygen species is increased, and the glutathione content is decreased in paracetamol overdose. Oxidative stress in mitochondria leads to mito?chondrial dysfunction with adenosine triphosphate depletion, increase mitochondrial permeability transition, deoxyribonu?cleic acid fragmentation which contribute to the development of hepatocellular necrosis in the liver after paracetamol overdose. Role of Kupffer cells in paracetamol-induced liver injury. Paracetamol activates Kupffer cells, which then release numerous cytokines and signalling molecules, including nitric oxide and superoxide. Kupffer cells are important in peroxynitrite formation. On the other hand, the activated Kupffer cells release anti-inflammatory cytokines. Role of neutrophils in paracetamol-induced liver injury. Paracetamol-induced liver injury leads to the accumulation of neutrophils, which release lysosomal enzymes and generate superoxide anion radicals through the enzyme nicotinamide adenine dinucleotide phosphate oxidase. Hydrogen peroxide, which is influenced by the neutrophil-derived enzyme myeloperoxidase, generates hypochlorus acid as a potent oxidant. Role of peroxynitrite in paracetamol-induced oxidative stress. Superoxide can react with nitric oxide to form peroxynitrite, as a potent oxidant. Nitrotyrosine is formed by the reaction of tyrosine with peroxynitrite in paracetamol hepatotoxicity. Conclusion. Overdose of paracetamol may produce severe liver injury with hepatocellular necrosis. The most important mechanisms of cell injury are metabolic activation of paracetamol, glutathione depletion, alkylation of proteins, especially mitochondrial proteins, and formation of reactive oxygen/nitrogen species.

Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120

2016 ◽  
Vol 23 (21) ◽  
pp. 21805-21821 ◽  
Author(s):  
Manish Singh Kaushik ◽  
Meenakshi Srivastava ◽  
Alka Srivastava ◽  
Anumeha Singh ◽  
Arun Kumar Mishra
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Iron Deficiency ◽  
Anabaena 7120 ◽  
Cyanobacterium Anabaena ◽  
Damaging Effects

Reactive oxygen intermediate production by oyster hemocytes exposed to hypoxia

1999 ◽  
Vol 202 (22) ◽  
pp. 3135-3143 ◽  
Author(s):  
J.N. Boyd ◽  
L.E. Burnett
Keyword(s):  
Reactive Oxygen ◽  
Reactive Oxygen Intermediate ◽  
Reactive Oxygen Intermediates ◽  
Oxygen Intermediates ◽  
Hypoxic Conditions ◽  
Enhanced Chemiluminescence ◽  
Large Numbers ◽  
Lower Oxygen ◽  
Independent Effects

Oysters are frequently exposed to severely hypoxic conditions, especially during summer months. During the summer, there are also large numbers of disease-related oyster mortalities. This research was conducted to determine whether exposure to environmental hypoxia reduces the ability of oyster hemocytes to produce reactive oxygen intermediates (ROIs), an important part of their defense system. Oysters of the species Crassostrea virginica were held in normoxic (P(O)(2)=20.0-20.7 kPa, pH 7.8-8.0) and hypoxic conditions (P(O)(2)=4.0-6.7 kPa, pH 7.1-7.4). In vivo hemolymph variables (P(O)(2), P(CO)(2) and pH) were measured after both 1 hour and 2 days in each treatment to determine the appropriate environment for subsequent hemocyte experiments. Production of reactive oxygen intermediates by hemocytes was measured using luminol-enhanced chemiluminescence (CL). During CL tests, hemocytes were held under the following conditions: air (P(O)(2)=20.7, P(CO)(2)&lt;0.07, pH 7.6), in vivo hemolymph conditions of normoxic oysters (P(O)(2)=5.2, P(CO)(2)=0.27, pH 7.6), and in vivo hemolymph conditions of hypoxic oysters (P(O)(2)=1.47, P(CO)(2)=0.53, pH 7.1). Production of ROIs under hypoxic conditions was 33 % of that under normoxia. This decrease was the result of specific and independent effects of lower oxygen levels and decreased pH. It was not due to any direct effect of CO(2).

scholarly journals Serum factor requirement for reactive oxygen intermediate release by rabbit alveolar macrophages.

1985 ◽  
Vol 161 (2) ◽  
pp. 392-408 ◽  
Author(s):  
G F Gerberick ◽  
J B Willoughby ◽  
W F Willoughby
Keyword(s):  
Alveolar Macrophages ◽  
Tissue Injury ◽  
Reactive Oxygen ◽  
Rabbit Serum ◽  
Reactive Oxygen Intermediate ◽  
Serum Free Medium ◽  
Free Medium ◽  
Oxygen Intermediates ◽  
Serum Free ◽  
Mediator Systems

Alveolar macrophages (AM) from pathogen-free rabbits were unable to release reactive oxygen intermediates (ROI) unless they were conditioned in serum for 24-48 h before triggering with membrane-active agents. The degree of serum conditioning of AM depended upon the concentration of serum used; optimal ROI release was obtained at or above 7.5% fetal bovine serum (FBS). FBS, autologous rabbit serum, pooled rabbit serum, and pooled human serum were each capable of conditioning AM for release of ROI. Serum conditioning of AM requires synthesis of new protein(s); and the enzyme required for ROI production, NADPH oxidase, was only detectable in serum-conditioned cells. Moreover, serum-conditioned cells lost their ability to release ROI after transfer to serum-free medium, while cells maintained in serum-free medium acquired the capacity to release ROI after their transfer to serum-containing medium, demonstrating the reversibility of the phenomenon. Initial purification data indicate that conditioning is mediated by a discrete serum constituent, which precipitates 40-80% saturated ammonium sulfate, does not bind to Cibacron Blue columns, and has a molecular weight of 30,000 to 50,000, as determined by molecular exclusion chromatography. Unlike gamma interferon, which also enhances ROI release by macrophages, our serum-conditioning factor is not acid labile, retaining 67% of its activity after 120 min incubation at pH 2.0. Moreover, it does not appear to be a contaminating endotoxin, since LPS neither conditioned AM for ROI production, nor triggered ROI production by serum-conditioned AM. We propose that such a conditioning requirement may normally protect the lung against ROI-mediated tissue injury. However, during a pulmonary inflammatory reaction initiated by other mediator systems, the resulting transudation of plasma proteins into the alveolar spaces may condition AM in situ for ROI production.

Tobacco-smoke-inducible human haem oxygenase-1 gene expression: role of distinct transcription factors and reactive oxygen intermediates

2001 ◽  
Vol 353 (3) ◽  
pp. 475-482 ◽  
Author(s):  
Florence FAVATIER ◽  
Barbara S. POLLA
Keyword(s):  
Gene Expression ◽  
Heat Shock ◽  
Tobacco Smoke ◽  
Reactive Oxygen ◽  
Binding Activity ◽  
Reactive Oxygen Intermediate ◽  
Mobility Shift ◽  
Oxygen Intermediates ◽  
Haem Oxygenase

Exposure of eukaryotic cells to a variety of reactive-oxygen-intermediate (ROI)-mediated sources of cellular injury, including heavy metals and UV radiation, induces the expression of heat-shock (HS) and stress-related genes among which is a 32–34kDa protein identified as inducible haem oxygenase-1 (HO-1). We previously showed that tobacco smoke (TS), a potent source of oxidants leading to oxidative stress, induces both HS proteins (HSPs) and HO-1 in normal human monocytes. Here we investigated the induction mechanisms of human HO-1 gene expression by TS in the human premonocytic line U937. Northern blotting and flow cytometry revealed a dose- and time-dependent induction of HO-1 mRNA and protein by TS. In order to clarify the role of transacting factors in this induction, electrophoretic mobility-shift analysis was performed with nuclear extracts from control, TS-, cadmium (Cd)- or H2O2-exposed cells, incubated with consensus elements and binding sites of the promoter region of HO-1[heat-shock factor (HSF), nuclear factor κB (NF-κB) and activator protein-1 (AP-1)] and the cadmium-responsive element (CdRE) isolated by Takeda, Ishizawa, Sato, Yoshida and Shibahara [(1994) J. Biol. Chem. 269, 22858–22867]. We report an inhibition of NF-κB activation by TS, no effect on AP-1 and a strong activation of CdRE-binding activity, whereas cadmium chelation from TS only partially prevented HO-1 induction. H2O2 also activated the CdRE-binding activity, and pretreatment with N-acetyl-l-cysteine, which replenishes the intracellular levels of GSH, suppressed, in TS-treated cells, both the CdRE-binding activity and the increased HO-1 expression.

scholarly journals Reactive Oxygen Species (ROS) Metabolism and Nitric Oxide (NO) Content in Roots and Shoots of Rice (Oryza sativa L.) Plants under Arsenic-Induced Stress

Agronomy ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1014 ◽  
Author(s):  
Ernestina Solórzano ◽  
Francisco J. Corpas ◽  
Salvador González-Gordo ◽  
José M. Palma
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Oryza Sativa ◽  
Oryza Sativa L ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antioxidative Systems ◽  
Ros Metabolism ◽  
As Stress

Arsenic (As) is a highly toxic metalloid for all forms of life including plants. Rice is the main food source for different countries worldwide, although it can take up high amounts of As in comparison with other crops, showing toxic profiles such as decreases in plant growth and yield. The induction of oxidative stress is the main process underlying arsenic toxicity in plants, including rice, due to an alteration of the reactive oxygen species (ROS) metabolism. The aim of this work was to gain better knowledge on how the ROS metabolism and its interaction with nitric oxide (NO) operate under As stress conditions in rice plants. Thus, physiological and ROS-related biochemical parameters in roots and shoots from rice (Oryza sativa L.) were studied under 50 μM arsenate (AsV) stress, and the involvement of the main antioxidative systems and NO in the response of plants to those conditions was investigated. A decrease of 51% in root length and 27% in plant biomass was observed with 50 μM AsV treatment, as compared to control plants. The results of the activity of superoxide dismutase (SOD) isozymes, catalase, peroxidase (POD: total and isoenzymatic), and the enzymes of the ascorbate–glutathione cycle, besides the ascorbate and glutathione contents, showed that As accumulation provoked an overall significant increase of most of them, but with different profiles depending on the plant organ, either root or shoot. Among the seven identified POD isozymes, the induction of the POD-3 in shoots under As stress could help to maintain the hydrogen peroxide (H2O2) redox homeostasis and compensate the loss of the ascorbate peroxidase (APX) activity in both roots and shoots. Lipid peroxidation was slightly increased in roots and shoots from As-treated plants. The H2O2 and NO contents were enhanced in roots and shoots against arsenic stress. In spite of the increase of most antioxidative systems, a mild oxidative stress situation appears to be consolidated overall, since the growth parameters and those from the oxidative damage could not be totally counteracted. In these conditions, the higher levels of H2O2 and NO suggest that signaling events are simultaneously occurring in the whole plant.

Oxidative Stress and Pteridines in Pediatric Asthma: Relationship to Exhaled Nitric Oxide

Pteridines ◽  
2012 ◽  
Vol 23 (1) ◽  
pp. 104-109 ◽  
Author(s):  
Taisuke Takeda ◽  
Takashi Hamazaki ◽  
Ryohei Wakahara ◽  
Hiroki Fujioka ◽  
Shizuhiro Niihira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Pediatric Asthma ◽  
Allergic Inflammation ◽  
Reactive Oxygen ◽  
Exhaled Nitric Oxide ◽  
Oxidative Stress Marker ◽  
Reactive Oxygen Metabolites ◽  
Asthmatic Patients ◽  
Airway Injury

Abstract Fractional exhaled nitric oxide (FeNO) is a useful marker of airway inflammation in asthmatics. Nitric oxide synthase (NOS) requires tetrahydrobiopterin as a cofactor and produces superoxide during NO generation. Therefore, we investigated the relationship of FeNO to pteridine biosynthesis and oxidative stress in pediatric asthma patients. We recruited 67 asthmatic children for FeNO measurement and examined neopterin, biopterin, and Diacron-reactive oxygen metabolites (d-ROMs) as an oxidative stress marker in both summer and winter. Although d-ROMs levels did not show significant correlation with FeNO levels in summer, d-ROMs and FeNO were positively correlated in winter (p <0.05). Both neopterin and biopterin levels in the blood tended to be lower in patients who showed higher FeNO. Multivariate analysis revealed that increased IgE levels correlated with increased FeNO (p <0.01) and decreased neopterin (p <0.05) levels. This data supports a mechanism by which decreased levels of pteridines promote reactive oxygen species production upon NO generation, resulting in airway injury in asthmatic patients. Correlation with IgE level indicates that Th2-mediated allergic inflammation is involved in this process.

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