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)

Granulocyte functions, viz. endocytosis, NADPH oxidase activity and iodination by leukocytes, were studied in granulocytes isolated from 17 chronic myeloid leukemia (CML) patients at initial diagnosis (stage I), from 10 patients in relapse (stage II), and 10 patients in acute blastic crisis (stage III). The mean phagocytic index of granulocytes from CML patients was similar to the normal value. NADPH activity decreased as the disease progressed. Thus, the amount of formazan produced was lower in granulocytes from patients in stage II (P less than 0.05) and stage III (P less than 0.01) than that produced by normal granulocytes. H2O2-Myeloperoxidase-dependent iodination was found to be significantly reduced in granulocytes from all stages of the disease compared to that of normal, stage I (P less than 0.01), stage II (P less than 0.05) and stage III (P less than 0.01). It thus seems that granulocyte function becomes less efficient as the disease progresses towards acute blastic crisis. Immature cells from the same patients carried out these functions at a more reduced level than did their mature counterparts.
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PMID:Studies on granulocyte functions in patients with chronic myeloid leukemia. 386 54

Cetiedil, alpha-cyclohexyl-3-thiopheneacetic acid 2-(hexahydro-lH-azepin-l-yl)-ethyl ester, was found to specifically suppress oxygen uptake by polymorphonuclear leucocytes (PMN) that were exposed to myristate or heat-killed E. coli. The chemical had no effect on the basal respiration rate of PMN in the resting state. Inhibition of oxygen uptake by cetiedil was proportionate to the degree of inhibition of the generation of O-2 and H2O2. It was also found that cetiedil suppressed the rate of the phagocytosis by PMN of opsonized oil droplets. Cetiedil had no effect on subcellular NADPH oxidase, an enzyme responsible for the respiratory burst that is activated by the perturbation of PMN plasma membrane with phagocytable particles or stimulators such as myristate. These results suggest that cetiedil affects the trigger mechanism of the plasma membrane to inhibit the activation of NADPH oxidase.
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PMID:Effects of cetiedil on the oxidative metabolism of activated polymorphonuclear leucocytes. 401 89

In thyroid gland, iodination takes place on the apical plasma membrane and requires the presence of the thyroid peroxidase and H2O2 generating system. H2O2 generation and NBT (nitro blue tetrazolium) reductase activity (both of which are NADPH-dependent) as well as peroxidase activity were compared for their respective orientations in membrane vesicles. The possible role of NADPH-NBT reductase activity in H2O2 generation was also examined. Results favor the conclusion that thyroid peroxidase is oriented towards the luminal side of the vesicles, whereas the NADPH site of NADPH oxidase-dependent H2O2 generation is located on the external side of the same or of different vesicles. Furthermore, it is shown that different NADPH-NBT reductase activities are present on both the outer and inner surfaces of the membrane vesicles, and that none of these activities is able to produce either H2O2 or O-2. The idea that a multi-component complex is involved in H2O2 generation is discussed, and a model is proposed which takes into account the possible spatial separation of the thyroid peroxidase site from the NADPH site of this H2O2 generation system on the apical membrane of the thyrocyte.
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PMID:Relation between thyroid peroxidase, H2O2 generating system and NADPH-dependent reductase activities in thyroid particulate fractions. 401 97

The extracellular protein coat of the sea urchin egg is cross-linked after fertilization via dityrosyl linkages made by an exocytosed ovoperoxidase. The source of oxidant for this reaction is unknown, but eggs produce H2O2 in amounts equivalent to the cyanide-insensitive O2 uptake "respiratory burst" that follows fertilization. Several possible H2O2-forming oxidase activities, including glucose, xanthine, fatty acyl, and fatty-acyl CoA oxidases, were absent from the egg cortex. However, an NAD(P)H-O2 oxidoreductase activity was found in the egg cortex and was completely accounted for by ovoperoxidase. Homogeneous ovoperoxidase exhibits two types of NAD(P)H oxidase activity. One of these activities is similar to that of horseradish peroxidase and lactoperoxidase; it is dependent on Mn2+ ions and catalytic amounts of phenols, such as 2,4-dichlorophenol and N-acetyltyrosinamide, and is greater than 95% inhibited by 0.1 mM cyanide. A second, novel oxidase activity utilizes Ca2+ and an unidentified, heat-stable, Mr less than 1000 factor that can be extracted by ethanol from egg homogenates. This NADH oxidase activity is only 40% inhibited by 0.1 mM cyanide and is maximally stimulated by 10 mM Ca2+. It has an apparent Km for NADH of 50 microM. The stoichiometry of NADH:O2 consumption is 1.6:1, but approaches 2:1 in the presence of 20 micrograms/ml superoxide dismutase or 200 micrograms/ml catalase. This indicates that complete reduction of O2 to water occurs and that the reaction does not produce H2O2 stoichiometrically. However, nearly complete inhibition of the reaction by higher catalase concentrations suggests that H2O2 is an intermediate. The properties of this novel oxidase activity suggest that it may play such a role in vivo.
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PMID:The relationship between a novel NAD(P)H oxidase activity of ovoperoxidase and the CN- -resistant respiratory burst that follows fertilization of sea urchin eggs. 405 35

The paper deals with 1) the features of the respiratory burst (increase of the respiration with production of O2 metabolites, O2-, H2O2, OH) of the inflammatory cells; 2) the factors responsible for its activation; 3) the methods for its measurement; 4) the molecular events which take place at the level of the plasma membrane following the interaction between the stimuli and the cell surface (the Ca++ changes, the modification of membrane potential, the activation of phospholipid turnover) and the hypothesis of the activation of the protein kinase C; 5) the nature of the NADPH oxidase whose activation is responsible for the respiratory burst and the production of O2 metabolites; 6) the defensive, toxic, proinflammatory and modulatory effects due to the reactivity of the oxygen metabolites.
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PMID:Mechanism of production of toxic oxygen radicals by granulocytes and macrophages and their function in the inflammatory process. 405 21

The origin of luminol-dependent chemiluminescence (CL) in neutrophils stimulated by immune complexes (IC) was investigated. It was found that CL induced by soluble IC and aggregated human gamma globulin (AHG) was glucose-independent, while insoluble IC-induced CL was diminished in the absence of glucose. AHG-induced CL was not inhibited by superoxide dismutase, catalase or 2,5-dimethyl furan, but was suppressed in the presence of phenol, sodium benzoate, sodium formate and mannitol. The CL was also inhibited by inhibitors of arachidonic acid (AA) metabolism including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin and aspirin, and by prostaglandins E1 and E2, theophylline and dibutyryl cyclic AMP. Luminol-dependent CL was also studied in cell-free systems including AA plus soybean lipoxygenase, hydroperoxyeicosatetraenoic acid plus peroxidase and xanthine oxidase plus xanthine. Our results indicate that, in neutrophils exposed to soluble IC and AHG, CL is produced and this is closely linked to the formation of free radicals during the metabolism of AA. The radical(s) involved is likely to include the hydroxyl radical. In neutrophils stimulated by large aggregates of IC or micro-organisms, superoxide anion, H2O2 and singlet oxygen are also produced as a result of activation of NAD(P)H oxidase. These oxygen species function as oxidizing agents for AA metabolism and amplify the production of hydroxyl radical along the lipoxygenase (and possibly cyclooxygenase) pathway(s).
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PMID:Luminol-dependent chemiluminescence produced by neutrophils stimulated by immune complexes. 608 70

The oxidative metabolism of rabbit alveolar macrophages (A-MO) was compared with that of rabbit polymorphonuclear leukocytes (PMN) with respect to H2O2 generation by intact cells or subcellular fractions. Rabbit PMN exhibited an increase in the oxygen uptake and a marked release of H2O2 upon addition of heat-killed E. coli in the presence and absence of opsonin. However, rabbit A-MO exhibited an increase in the oxygen uptake upon addition of E. coli only in the presence of anti-E. coli serum as an opsonin, whereas a very small amount of H2O2 release was observed during ingestion of the opsonized E. coli. The generation of O2- and H2O2 by a granule-rich fraction isolated from phagocytosing PMN was larger than that by a similar fraction isolated from resting PMN. However, there was no significant difference in O2- and H2O2 generation by the granule fractions between phagocytosing and resting A-MO in the presence of either NADH or NADPH. In contrast to the granule fraction of rabbit PMN, the O2- and H2O2 generating activities in the A-MO granule fraction were higher in the presence of NADH than in the presence of NADPH. The rates of NADH and NADPH oxidation by both A-MO and PMN granule fractions were measured with and without addition of Mn2+ to the assay medium. The effect of Mn2+ on the NAD(P)H oxidase was found to differ between rabbit A-MO and PMN.
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PMID:Comparative studies on alveolar macrophages and polymorphonuclear leukocytes. I. H2O2 and O2- generation by rabbit alveolar macrophages. 624 9

1. The so called "soluble" oxidase(s) are not involved in the respiratory burst of guinea pig and human granulocytes and of guinea pig peritoneal resident and elicited macrophages. 2. The activation of the oxidation of NADPH by a membrane bound NAD(P)H oxidase is the main mechanism responsible for the activation of the respiration of phagocytes. 3. The oxidase is inactive in resting cells and the activated form works on the plasma membrane. 4. More than one mechanism is operative in the oxidation of NAD(P)H by cell free particles in vitro. These mechanisms vary in relation to the conditions of assay (pH and concentration of substrate). 5. Under optimal conditions in vitro the enzymatic oxidation of NADPH practically involves the univalent pathway of oxygen reduction with stoichiometry of two nanomoles of O2 formed for one nanomole of NADPH oxidized. 6. Also in intact cells all O2 is first univalently reduced to O2 and then discharged outside the cell or in the phagocytic vacuoles. 7. The main reactions involved in the O2 balance in intact cells are the univalent reduction of O2, the dismutation of O2 to H2O2 and the degradation of the peroxide through catalatic and peroxidatic mechanisms. 8. The total oxygen univalently reduced by the activated oxidase is 2-4 folds the net oxygen consumed by the cells, depending on the mechanism of H2O2 degradation. 9. All the rate of extrarespiration is accounted for by the rate of oxidation of physiological concentration of NADPH by the membrane-bound enzyme. This adequacy can be observed only under appropriate experimental conditions, because the high activity of the oxidase is not a permanent state.
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PMID:The respiratory burst of phagocytic cells: facts and problems. 628 27

These studies on the effect of administration of 1,600 units of vitamin E to humans indicated the following responses to the PMNs (TABLE 6). Functional alterations occur with an increased ability to ingest particles but a mild decrease in bactericidal potency of the PMN. Although the respiratory burst is slightly enhanced as is superoxide anion release, H2O2 release from the PMN is markedly impaired. The hexose monophosphate shunt activity, which is dependent on intracellular H2O2 is decreased during phagocytosis. Membrane responses such as changes in order parameter during phagocytosis as reported by the stearic acid analogue probe 5DS are similar to those of normal PMNs. The release of arachidonic acid from membranes of vitamin E PMNs during phagocytosis of opsonized zymosan is slightly enhanced, indicating normal phospholipase A2 activation. NADH oxidase-derived H2O2 is not impaired within phagocytic generated by NADPH oxidase in phagocytic vesicles, accounting for impairment in HMPS activity and bactericidal activity in these cells.
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PMID:The influence of vitamin E on human polymorphonuclear cell metabolism and function. 629 63

Mouse peritoneal macrophages respond to environmental stimuli in different ways depending on their state of differentiation. Macrophages from mice with bacillus Calmette--Guerin (BCG) infection produced large amounts of H2O2 in response to phorbol diesters (PDEs), while those from noninfected mice produced little or no H2O2. The effects of PDEs on cells are mediated by specific cellular receptors for these ligands. The purpose of this study was to determine if the varying responses of macrophages from different groups of mice were caused by differences in their receptors for the PDE ligands. By all parameters studied, the binding of [20-3H]phorbol 12,13-dibutyrate ( [3H]PDBu) was similar in all macrophages irrespective of their ability to produce H2O2 in response to PDEs. Binding of [3H]PDBu was rapid at 23 degrees C reaching a maximum at 10-20 min with a subsequent decline to 50-60% of maximum by 30-60 min. Binding was slower at 0 degrees C reaching a maximum at 90-120 min. The binding was reversible, with dissociation kinetics paralleling association kinetics. The binding was saturable; the Kd's (45 to 91 nM) and number of binding sites (about 7-14 X 10(5)/cell or 11-12 pmol/mg protein) were essentially the same for the different classes of macrophages. The binding was specific, and analogs of PDBu inhibited [3H]PDBu binding to macrophages with potencies comparable to their potencies in causing in vivo tumor promotion and elicitation of other cellular responses in vitro. The ligands [3H]PDBu and [3H]PMA were degraded to comparable degrees by macrophages from normal or BCG-infected mice. Macrophages from C3H/HeJ and C3H/HeN mice, although known to differ in their abilities to respond to stimuli such as lymphokines and LPS, did not differ in their ability to produce H2O2 in response to PDEs or in their receptors for PDEs. Results of this study suggest that in vivo "activation" of macrophages in mice infected with BCG is not associated with a change in the cells' receptors for PDEs, but may be associated with "postreceptor" changes such as linkage of the PDE receptor with NAD(P)H oxidase, a change in NAD(P)H oxidase, or induction of synthesis of NAD(P)H oxidase.
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PMID:Phorbol diester-induced H2O2 production by peritoneal macrophages. Different H2O2 production by macrophages from normal and BCG-infected mice despite comparable phorbol diester receptors. 630 16


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