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

---

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

Isopycnic sedimentation has been used to separate granulocytes of varying stages of maturity from the bone marrows of normal rabbits and rabbits stimulated to undergo an intense inflammatory response. The separated cell populations were in turn utilized to study the specific activities of six intracellular enzymes. The study revealed an increase with cell maturation in the specific activities of myeloperoxidase, NADPH oxidase, alkaline phosphatase and acid phosphatase in normal animals; in stimulated animals only myeloperoxidase and NADPH oxidase increased significantly with cell maturation. Glucose-6-phosphate dehydrogenase showed no change in specific activity in all animals studied. Malate dehydrogenase tended to show a specific activity decrease in the maturing cells of normal but not in those of stimulated animals.
...
PMID:Characterization of marrow granulocyte development: enzyme-specific activity profiles in response to inflammatory reactions. 2 66

An assay method for the simultaneous evaluation of the oxidative metabolism and adherence of human neutrophils is described, together with certain specific applications. Incubations were performed in serum-coated microtiter plates, where oxidative metabolism was measured as O2- release and, after washing out the nonadherent cells, the adhesion was measured as activity of acid phosphatase. Three agonists tested in this system--opsonized zymosan, concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine--induced both activation of O2- release and cell adhesion, but the two functions had time course and dose dependence patterns that varied depending on the stimulant. Particularly with concanavalin A, O2- release and adhesion response were markedly dissociated; this lectin at low doses increased neutrophil adherence without triggering any O2- production, whereas at high doses it increased both O2- production and adherence. Anti-integrin monoclonal antibodies did not affect adhesion induced by low-dose concanavalin A but inhibited the adhesion induced by the other tested agonists. Adhesion and O2- production were also found to be differentially affected by the NADPH oxidase inhibitor diphenylene iodonium, the sulfhydryl reagent N-ethylmaleimide and the A2 agonist adenosine, indicating that these neutrophil responses have various transductional pathways that also depend on the type of stimulus.
...
PMID:Simultaneous assay for oxidative metabolism and adhesion of human neutrophils: evidence for correlations and dissociations of the two responses. 134 79

Inflammatory response has been assessed in riboflavin or pyridoxine deficient rats. Edema was increased by 54% in pyridoxine deficiency as compared to weight-matched control rats. Food restriction per se reduced the volume of edema by 63%. In pyridoxine deficiency, concentrations of thiobarbituric acid reactive substances (which indicate the extent of lipid peroxidation) increase by 30 and 43% respectively in the edematous tissues of the paw as well as in the wounded skin. Both these parameters were not affected by riboflavin deficiency. Activities of NADPH oxidase and superoxide dismutase in elicited leukocytes from peritoneal cavity were reduced by 54 and 52%, respectively, in riboflavin deficiency but were unaltered in pyridoxine deficiency. Superoxide level and acid phosphatase activity were not influenced by either of the deficiencies, whereas hydrogen peroxide level was increased by 48% in riboflavin deficiency. Food restriction did not affect leukocyte enzymes or the levels of reduced oxygen species. The data suggest that inflammation is enhanced in pyridoxine deficiency but not in riboflavin deficiency.
...
PMID:Effect of riboflavin or pyridoxine deficiency on inflammatory response. 181 86

1. Enzymes pertinent to bactericidal activities of leucocytes were assayed in children suffering from protein-calorie malnutrition. 2. Leucocytes obtained from malnourished and control children contained similar activities for glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Granule-bound NADPH oxidase activity was low in leucocytes isolated from malnourished patients and failed to show the phagocytic stimulation which is normally seen in control leucocytes. Further, leucocytes obtained from malnourished patients did not release the acid phosphatase from lysosomes during phagocytosis, unlike those from controls. 3. Treatment of the malnourishment with a diet high in calories and protein resulted in significant increase in the activities of glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADPH oxidase and in releasing the acid phosphatase from the lysosomes into the supernatant fraction during phagocytosis. 4. The significance of these enzyme changes are discussed in relation to the increased susceptibility of these patients to infection.
...
PMID:Phagocytosis and leucocyte enzymes in protein-calorie malnutrition. 440 28

All of the common cytochalasins activate superoxide anion release and exocytosis of beta-N-acetylglucosaminidase and lysozyme from guinea-pig polymorphonuclear leukocytes (neutrophils) incubated in a buffered sucrose medium. Half-maximal activation of both processes is produced by approx. 0.2 microM cytochalasin A, C greater than 2 microM cytochalasin B greater than or equal to 4-5 microM cytochalasin D, E. While maximal rates of O2- release and extents of exocytosis require extracellular calcium (1-2 mM), replacing sucrose with monovalent cation chlorides is inhibitory to neutrophil activation by cytochalasins. Na+, K+ or choline inhibit either cytochalasin B- or E-stimulated O2- production with IC50 values of 5-10 mM and inhibition occurs whether Cl-, NO3- or SCN- is the anion added with Na+ or K+. Release of beta-N-acetylglucosaminidase in control or cytochalasin B-stimulated cells is inhibited by NaCl(IC50 approximately 10 mM), while cytochalasin E-stimulated exocytosis is reduced less and K+ or choline chloride are ineffective in inhibiting either cytochalasin B- or E-stimulated exocytosis. Release of beta-glucuronidase, myeloperoxidase or acid phosphatase from neutrophils incubated in buffered sucrose is not stimulated by cytochalasin B. Stimulation of either O2- or beta-N-acetylglucosaminidase release by low concentrations of cytochalasin A is followed by inhibition of each at higher concentrations. It appears that all cytochalasins can activate both NAD(P)H oxidase and selective degranulation of neutrophils incubated in salt-restricted media and that differential inhibition of these two processes by monovalent cations and/or anions is produced at some step(s) subsequent to cytochalasin interaction with the cell.
...
PMID:Activation of superoxide production and differential exocytosis in polymorphonuclear leukocytes by cytochalasins A, B, C, D and E. Effects of various ions. 627 16

Pyelonephritis is the most common urinary tract infection affecting females of all age groups. Despite concerted efforts the mechanism of renal injury in pyelonephritis is not clearly understood. In the present study we have made an attempt to characterise the mediators of inflammatory insult in an experimental model of ascending pyelonephritis. Mice infected with Escherichia coli O6:K13:H1 were sacrificed at 2, 7 and 14 days post-infection. Luminol-dependent chemiluminescence response, NADPH oxidase, acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase activities were monitored in circulating as well as renal phagocytic cells in order to determine the role of reactive oxygen species and lysosomal enzymes in genesis of renal injury. We have demonstrated that reactive oxygen species are generated at the initiation of infection and the levels increase progressively during the course of infection. While intracellular release of lysosomal enzymes was seen in all groups, extracellular release was primarily observed at 7 and 14 days post-infection only. The results indicate that while reactive oxygen species play a significant role in tissue injury during all stages of infection, lysosomal enzyme release in extracellular milieu augments tissue destruction at later stages only.
...
PMID:Oxygen-dependent and -independent mechanisms of renal injury in experimental ascending pyelonephritis. 882 96

Diphenyleneiodonium (DPI) inhibits activity of flavoenzymes like NADPH oxidase, the major source of superoxide anion in cardiovascular system, but affects also other oxidoreductases. Contradictory data have been published concerning the effect of diphenyleneiodonium on the production of reactive oxygen species in cells, both inhibitory and stimulatory action of DPI being reported. We have examined the effect of DPI on the cellular production of reactive oxygen and nitrogen species (ROS/RNS) and on the proliferation and apoptosis of human vascular endothelial cells. We found increased oxidation of ROS-sensitive probes (dihydrorhodamine 123 and 2',7'-dichlorodihydrofluorescein diacetate) when DPI (20 microM-100 microM) was present in the treated cells. However, oxidation of the fluorogenic probes was inhibited if DPI (20 microM-100 microM) was removed from the reaction medium after cell preincubation. These results suggest an artifactual oxidation of the fluorogenic probes by DPI or its metabolites. A similar pattern of influence of DPI on the production of NO (measured with 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate) was observed. Modulation of generation of reactive oxygen and nitrogen species in DPI-treated cells influenced the nitration of tyrosine residues of cellular proteins, estimated by Western blotting. Decreased level of nitration generally paralleled the lowered production of ROS. A decreased 3-(4,5-dimethylthiazolyl)-3-3(4-sulphophenyl) tetrazolium (MTT) reducing activity of cells for was observed immediately after 1h treatment of human endothelial cells with DPI (1 microM-100 microM), in spite of lack of changes in cell viability estimated by other methods. These results point to a next limitation of MTT in estimation of viability of cells treated with oxidoreductase inhibitors. DPI inhibited the proliferation of HUVECs as well as immortalized cell line HUVEC-ST, as assessed by acid phosphatase activity test and measurement of total nucleic acid content. Proapoptotic action of DPI was observed 12 h after incubation with this compound.
...
PMID:Induction of apoptosis and modulation of production of reactive oxygen species in human endothelial cells by diphenyleneiodonium. 1579 48

Reactive oxygen species (ROS) derived from NADPH oxidase (Nox) homologues have been suggested to regulate osteoclast differentiation. However, no bone abnormalities have been documented in Nox1 deficient, Nox2 deficient, or Nox3 mutant mice. During receptor activator of nuclear factor-kappaB ligand (RANKL)-stimulated differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts, mRNA levels of Nox enzymes (Nox1-4) and their adaptor proteins were monitored by real-time reverse transcriptase PCR. RAW264.7 cells constitutively expressed abundant Nox2 mRNA and small amounts of Nox1 and Nox3 transcripts. RANKL markedly attenuated Nox2 mRNA expression in association with reciprocal up-regulation of Nox1 and Nox3 transcripts. Introduction of small interference RNA targeting p67(phox) or p22(phox) into RAW264.7 cells effectively down-regulated ROS generation and significantly suppressed the RANKL-stimulated differentiation, which was assessed by appearance of tartrate resistant acid phosphatase (TRAP)-positive, multinucleated cells having an ability to form resorption pits on calcium phosphate thin film-coated disks, and by expression of osteoclast marker genes (TRAP, cathepsin K, Atp6i, ClC-7, and NFATc1). Our results suggest that RANKL may stimulate switching between Nox homologues during osteoclast differentiation, and Nox-derived ROS may be crucial for RANKL-induced osteoclast differentiation.
...
PMID:NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts. 1926 12

Ft is a facultative intracellular pathogen that infects many cell types, including neutrophils. In previous work, we demonstrated that the type B Ft strain LVS disrupts NADPH oxidase activity throughout human neutrophils, but how this is achieved is incompletely defined. Here, we used several type A and type B strains to demonstrate that Ft-mediated NADPH oxidase inhibition is more complex than appreciated previously. We confirm that phagosomes containing Ft opsonized with AS exclude flavocytochrome b(558) and extend previous results to show that soluble phox proteins were also affected, as indicated by diminished phosphorylation of p47(phox) and other PKC substrates. However, a different mechanism accounts for the ability of Ft to inhibit neutrophil activation by formyl peptides, Staphylococcus aureus, OpZ, and phorbol esters. In this case, enzyme targeting and assembly were normal, and impaired superoxide production was characterized by sustained membrane accumulation of dysfunctional NADPH oxidase complexes. A similar post-assembly inhibition mechanism also diminished the ability of anti-Ft IS to confer neutrophil activation and bacterial killing, consistent with the limited role for antibodies in host defense during tularemia. Studies of mutants that we generated in the type A Ft strain Schu S4 demonstrate that the regulatory factor fevR is essential for NADPH oxidase inhibition, whereas iglI and iglJ, candidate secretion system effectors, and the acid phosphatase acpA are not. As Ft uses multiple mechanisms to block neutrophil NADPH oxidase activity, our data strongly suggest that this is a central aspect of virulence.
...
PMID:Multiple mechanisms of NADPH oxidase inhibition by type A and type B Francisella tularensis. 2061 Jul 96

Autophagy mediates the degradation of cytoplasmic contents in the lysosome and plays a significant role in immunity. Lipid second messengers have previously been implicated in the regulation of autophagy. Here, we demonstrate a signaling role for diacylglycerol (DAG) in antibacterial autophagy. DAG production was necessary for efficient autophagy of Salmonella, and its localization to bacteria-containing phagosomes preceded autophagy. The actions of phospholipase D and phosphatidic acid phosphatase were required for DAG generation and autophagy. Furthermore, the DAG-responsive delta isoform of protein kinase C was required, as were its downstream targets JNK and NADPH oxidase. Previous studies have revealed a role for the ubiquitin-binding adaptor molecules p62 and NDP52 in autophagy of S. Typhimurium. We observed bacteria-containing autophagosomes colocalizing individually with either DAG or ubiquitinated proteins, indicating that both signals can act independently to promote antibacterial autophagy. These findings reveal an important role for DAG-mediated PKC function in mammalian antibacterial autophagy.
...
PMID:A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy. 2070 89


1 2 Next >>

---