Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.3.1 (NADPH oxidase)
11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As plants are confined to the place where they grow, they have to develop a broad range of defence responses to cope with pathogenic infections. The oxidative burst, a rapid, transient, production of huge amounts of reactive oxygen species (ROS), is one of the earliest observable aspects of a plant's defence strategy. First this Review describes the chemistry of ROS (superoxide radical, hydrogen peroxide and hydroxyl radical). Secondly, the role of ROS in defence responses is demonstrated, and some important issues are considered, such as: (1) which of the ROS is a major building element of the oxidative burst; (2) the spatial and temporal regulation of the oxidative burst; and (3) differences in the plant's responses to biotic and abiotic elicitation. Thirdly, the relationships between the oxidative burst and other plant defence responses are indicated. These include: (1) an oxygen consumption, (2) the production of phytoalexins, (3) systemic acquired resistance, (4) immobilization of plant cell wall proteins, (5) changes in membrane permeability and ion fluxes and (6) a putative role in hypersensitive cell death. Wherever possible, the comparisons with models applicable to animal systems are presented. Finally, the question of the origin of ROS in the oxidative burst is considered, and two major hypotheses, (1) the action of NADPH oxidase system analogous to that of animal phagocytes, and (2) the pH-dependent generation of hydrogen peroxide by a cell wall peroxidase, are presented. On the basis of this material, a third 'unifying' hypothesis is presented, where transient changes in the pH of the cell wall compartment are indicated as a core phenomenon in evoking ROS production. Additionally, a germin/oxalate oxidase system which generates H2O2 in response to pathogenic infection is also described.
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PMID:Oxidative burst: an early plant response to pathogen infection. 914 37

Human neutrophils (PMN) activated by N-formylmethionyl-leucyl-phenylalanine (fMLP) simultaneously release nitric oxide (.NO), superoxide anion (O2.-) and its dismutation product, hydrogen peroxide (H2O2). To assess whether .NO production shares common steps with the activation of the NADPH oxidase, PMN were treated with inhibitors and antagonists of intracellular signaling pathways and subsequently stimulated either with fMLP or with a phorbol ester (PMA). The G-protein inhibitor, pertussis toxin (1-10 micrograms/ml) decreased H2O2 yield without significantly changing .NO production in fMLP-stimulated neutrophils; no effects were observed in PMA-activated cells. The inhibition of tyrosine kinases by genistein (1-25 micrograms/ml) completely abolished H2O2 release by fMLP-activated neutrophils; conversely, .NO production increased about 1.5- and 3-fold with fMLP and PMA, respectively. Accordingly, orthovanadate, an inhibitor of phosphotyrosine phosphatase, markedly decreased .NO production and increased O2.- release. On the other hand, inhibition of protein kinase C with staurosporine and the use of burst antagonists like adenosine, cholera toxin or dibutyryl-cAMP diminished both H2O2 and .NO production. The results suggest that the activation of the tyrosine kinase pathway in stimulated human neutrophils controls positively O2.- and H2O2 generation and simultaneously maintains .NO production in low levels. In contrast, activation of protein kinase C is a positive modulator for O2.- and .NO production.
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PMID:Effects of respiratory burst inhibitors on nitric oxide production by human neutrophils. 916 37

Chronic granulomatous disease is an uncommon inherited disease with presentations of frequent pyogenic and fungal infections. In this disease, the phagocytes ingest pathogens, but the ingested microorganisms can not be killed because the cells lack the ability to convert oxygen into superoxide using the enzyme known as NADPH oxidase. We report on a patient who had experienced frequent lymphadenopathy and bacterial infections since childhood. In addition to his history of repeated bacterial infections, diagnosis was also based on abnormal findings in immunologic tests including the nitroblue tetrazolium test assay, analysis of chemiluminescence and detection of hydrogen peroxide using flow cytometry. He received prophylactic treatment with antibiotics, and the condition remained stable during a six-month follow-up period.
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PMID:Chronic granulomatous disease: a case report. 926 Mar 77

The effects of arachidonic acid metabolism and NADPH oxidase inhibitor on the hydrogen peroxide (H2O2) generation and endocytotic activity of cultured human endothelial cells (EC) exposed to atherogenic low-density lipoprotein (LDL) levels have been investigated. EC were incubated with 240 mg/dl LDL cholesterol and cellular H2O2 production and endocytotic activity measured in the presence and absence of the arachidonic acid metabolism inhibitors, indomethacin, nordihydroguaiaretic acid, and SKF525A, and NADPH oxidase inhibitor, apocynin. All inhibitors, with the exception of indomethacin, markedly reduced high LDL-induced increases in EC H2O2 generation and endocytotic activity. EC exposed to exogenously applied arachidonic acid had cellular functional changes similar to those induced by high LDL concentrations. EC incubated with 1-25 uM arachidonic acid had increased H2O2 production and heightened endocytotic activity. Likewise, EC pre-loaded with [3H]arachidonic acid when exposed to increasing LDL levels (90-330 mg/dl cholesterol) had a dose-dependent rise in cytosolic [3H]arachidonic acid. The phospholipase A2 inhibitors, 4-bromophenacyl bromide and 7,7-dimethyleicosadienoic acid, markedly inhibited H2O2 production in EC exposed to 240 mg/dl LDL cholesterol. These findings suggest that arachidonic acid contributes mechanistically to high LDL-perturbed EC H2O2 generation and heightened endocytosis. Such cellular functional changes add to our understanding of endothelial perturbation, which has been hypothesized to be a major contributing factor in the pathogenesis of atherosclerosis.
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PMID:Low-density lipoprotein stimulated peroxide production and endocytosis in cultured human endothelial cells: mechanisms of action. 927 82

Neutrophils contain a 21-kDa phosphoprotein that undergoes rapid dephosphorylation upon stimulation of these cells with the chemoattractant N-fMet-Leu-Phe (fMLP), activators of protein kinase C [e.g., 4 beta-phorbol 12-myristate 13-acetate (PMA)] or the calcium ionophore A23187. This phosphoprotein was identified as the non-muscle form of cofilin by peptide sequencing and immunoblotting with specific antibodies. Evidence is presented that in neutrophils cofilin is regulated by a continual cycle of phosphorylation and dephosphorylation, and that the phosphatase undergoes activation during cell stimulation. Experiments with a wide variety of antagonists further suggested that the protein kinase that participates in these reactions may be a novel enzyme. The kinetics of cofilin dephosphorylation in neutrophils stimulated with fMLP or PMA were very similar to those observed for superoxide (O2-) release. Immunofluorescent studies revealed that cofilin was present throughout the cytosol of resting neutrophils and underwent rapid translocation to the F-actin-rich, ruffled membranes of stimulated cells. Cytochemical analysis further revealed that the ruffled membranes also contained large amounts of hydrogen peroxide (H2O2), a product of the O2-/H2O2-generating activity of stimulated neutrophils (NADPH oxidase). Cofilin is therefore well placed to participate in the continual polymerization and depolymerization of F-actin that is thought to give rise to the oscillatory pattern of H2O2 production observed under certain conditions.
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PMID:Cofilin undergoes rapid dephosphorylation in stimulated neutrophils and translocates to ruffled membranes enriched in products of the NADPH oxidase complex. Evidence for a novel cycle of phosphorylation and dephosphorylation. 934 16

We have investigated the action of the product of the enzyme NADPH oxidase; hydrogen peroxide (H2O2), on the first phase of the hypoxic contraction, prostaglandin F2 alpha (PGF2 alpha)-induced contractions and potassium chloride (KCl)-induced contractions, in isolated rat pulmonary arteries in a wire myograph. Both concentrations of H2O2 (0.03 and 0.5 mM) produced initial contractions, and the higher concentration of H2O2 produced a significant inhibition of both the priming concentration of PGF2 alpha (5 microM) and the hypoxic contraction (P < 0.01 for both contractions). These effects were shown to be reversible, with contractions of a similar size to control values being seen to both PGF2 alpha (5 microM) and hypoxia following washout of H2O2 (P > 0.1 for both contractions). H2O2 (0.03 mM) was shown to have no significant effect upon either contraction (P > 0.1 for both contractions). H2O2 (0.5 mM) was also shown to have a significant inhibitory effect upon the efficacy (Emax) of the PGF2 alpha and KCl concentration-response curves (P < 0.01 for both contractions). This inhibition was again shown to be reversible. The higher concentration of H2O2 (0.5 mM) is clearly shown to be having a dual action, producing an initial contraction followed by inhibition of contractions to both PGF2 alpha and KCl. The mechanism by which H2O2 produces vasoconstriction is unclear, but it is suggested that H2O2 may inhibit the release of Ca2+ ions from intracellular stores as this is a common link between the modes of action of these two contractile agents. In addition to this, as an elevation in intracellular Ca2+ from intracellular stores appears to be a prerequisite for hypoxic pulmonary vasoconstriction (HPV), then this apparent mode of action of H2O2 could play an important role in the regulation of HPV and suggests a possible role for NADPH oxidase or a similar oxidoreductase as an oxygen sensor.
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PMID:The effect of hydrogen peroxide on hypoxia, prostaglandin F2 alpha and potassium chloride induced contractions in isolated rat pulmonary arteries. 934 31

The enzymatic determination of hydrogen peroxide can be accomplished with high sensitivity and specificity using N-acetyl-3, 7-dihydroxyphenoxazine (Amplex Red), a highly sensitive and chemically stable fluorogenic probe for the enzymatic determination of H2O2. Enzyme-catalyzed oxidation of Amplex Red, which is a colorless and nonfluorescent derivative of dihydroresorufin, produces highly fluorescent resorufin, which has an excitation maximum at 563 nm and emission maximum at 587 nm. The reaction stoichiometry of Amplex Red and H2O2 was determined to be 1:1. This probe allows detection of 5 pmol H2O2 in a 96-well fluorescence microplate assay. When applied to the measurement of NADPH oxidase activation, the Amplex Red assay can detect H2O2 release from as few as 2000 phorbol myristate acetate-stimulated neutrophils with a sensitivity 5- to 20-fold greater than that attained in the scopoletin assay under the same experimental conditions. Furthermore, the oxidase-catalyzed assay using Amplex Red results in an increase in fluorescence on oxidation rather than a decrease in fluorescence as in the scopoletin assay. In comparison with other fluorometric and spectrophotometric assays for the detection of monoamine oxidase and glucose oxidase, this probe is also found to be more sensitive. Given its high sensitivity and specificity, Amplex Red should have a broad application for the measurement of H2O2 in a variety of oxidase-mediated reactions and very low levels of H2O2 in food, environmental waters, and consumer products.
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PMID:A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases. 936 98

The sites of generations of superoxide anions and hydrogen peroxide in cross sections of hypocotyls from spinach seedlings were located by staining with nitroblue tetrazolium (NBT) and with starch-iodide, respectively. Formazan, produced upon the reduction of NBT by superoxide, was observed mainly in the vascular tissue only in the presence of inhibitors of CuZn-superoxide dismutase (CuZn-SOD), and its formation was suppressed under anaerobic conditions. Thus, NBT was reduced to formazan specifically by the superoxide anions generated in vascular tissue. The reduction of NBT was suppressed by inhibitors of NAD(P)H oxidase, but neither by cyanide nor azide, indicating the involvement of NAD(P)H oxidase in the generation of superoxide anions in the vascular tissue. Starch-I2 complex also was formed in the vascular tissue, but not in the presence of either the CuZn-SOD inhibitor or the NAD(P)H oxidase inhibitor, indicating that the hydrogen peroxide is produced via the catalytic disproportionation with CuZn-SOD of the superoxide generated by NAD(P)H oxidase. Generations of superoxide anions and hydrogen peroxide in the vascular tissue were particularly apparent in the xylem and associated with the sites of distribution of CuZn-SOD as determined by an immunohistochemical method, and also with the location of lignin as determined by the phloroglucin-HCl reaction.
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PMID:Generation of superoxide anion and localization of CuZn-superoxide dismutase in the vascular tissue of spinach hypocotyls: their association with lignification. 939 35

The gene encoding a putative NADPH:flavin oxidoreductase of the protozoan parasite Entamoeba histolytica (Eh34) was recombinantly expressed in Escherichia coli. The purified recombinant protein (recEh34) has a molecular mass of about 35 kDa upon SDS/PAGE analysis, exhibits a flavoprotein-like absorption spectrum and contains 1 mol of non-covalently bound FMN per mol of protein. RecEh34 reveals two different enzymic activities. It catalyses the NADPH-dependent reduction of oxygen to hydrogen peroxide (H2O2), as well as of disulphides such as 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and cystine. The disulphide reductase but not the H2O2-forming NADPH oxidase activity is inhibitable by sulphydryl-active compounds, indicating that a thiol component is part of the active site for the disulphide reductase activity, whereas for the H2O2-forming NADPH oxidase activity only the flavin is required. Compared with the recombinant protein, similar activities are present in amoebic extracts. Native Eh34 is active in a monomeric as well as in a dimeric state. In contrast to recEh34, no flavin was associated with the native protein. However, both NADPH oxidase as well as DTNB reductase activity were found to be dependent on the addition of FAD or FMN.
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PMID:Recombinant expression and biochemical characterization of an NADPH:flavin oxidoreductase from Entamoeba histolytica. 949 88

Experiments were designed to investigate whether leukotriene (LTB4) receptors can couple directly to phospholipase A2 (PLA2) in guinea pig eosinophils and the role of endogenous arachidonic acid (AA) in LTB4-induced activation of the NADPH oxidase. LTB4 (EC50 approximately 16 nM) and AA (EC50 approximately 6 microM) generated hydrogen peroxide (H2O2) in a concentration-dependent manner and at an equivalent maximum rate (5-6 nmol/min/10(6) cells). LTB4 stimulated PLA2 over a similar concentration range that activated the NADPH oxidase, although kinetic studies revealed that the release of [3H]AA (t1/2 approximately 2 s) preceded H2O2 generation (t1/2 > 30 s). Pretreatment of eosinophils with pertussis toxin abolished the increase in inositol(1,4,5)trisphosphate mass, [Ca2+]c, [3H]AA release, and H2O2 generation evoked by LTB4. Qualitatively identical results were obtained in eosinophils in which phospholipase C (PLC) was desensitized by 4beta-phorbol 12,13-dibutyrate with the exception that [3H]AA release was largely unaffected. Additional studies performed with the protein kinase C inhibitor, Ro 31-8220, and under conditions in which Ca2+ mobilization was abolished, provided further evidence that LTB4 released [3H]AA independently of signal molecules derived from the hydrolysis of phosphatidylinositol(4,5)bisphosphate by PLC. Pretreatment of eosinophils with the PLA2 inhibitor, mepacrine, abolished LTB4-induced [3H]AA release at a concentration that inhibited H2O2 by only 36%. Collectively, the results of this study indicate that agonism of LTB4 receptors on guinea pig eosinophils mobilizes AA by a mechanism that does not involve the activation of PLC. In addition, although LTB4 effectively stimulated PLA2, a central role for AA in the activation of the NADPH oxidase was excluded.
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PMID:Leukotriene B4 activates the NADPH oxidase in eosinophils by a pertussis toxin-sensitive mechanism that is largely independent of arachidonic acid mobilization. 957 59


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