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:1.6.99.6 (NADPH oxidase)
10,295 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several reports have implicated reactive oxygen and nitrogen metabolites (RONS) in the initiation and/or progression of inflammatory bowel diseases (IBDs). We have investigated the role of three key RONS-metabolizing enzymes (inducible nitric oxide synthase [iNOS], superoxide dismutase [SOD], nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) in a murine model of IBD. Mice genetically deficient ((-/-)) in either iNOS or the p47phox subunit of NADPH oxidase, transgenic (Tg) mice that overexpress SOD, and their respective wild-type (WT) littermates were fed dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis. In addition, the specific iNOS inhibitor 1400W was used in DSS-treated WT and p47phox(-/-) mice. WT mice responded to DSS feeding with progressive weight loss, bloody stools, elevated serum NO(X) and colonic mucosal injury with neutrophil infiltration. Both the onset and severity of colitis were significantly attenuated in iNOS(-/-) and 1400W-treated WT mice. While the responses to DSS did not differ between WT and p47phox(-/-) mice, enhanced protection was noted in 1400W-treated p47phox(-/-) mice. Interestingly, SOD(Tg) mice exhibited more severe colitis than their WT littermates. These findings reveal divergent roles for superoxide and iNOS-derived NO in intestinal inflammation.
...
PMID:Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of superoxide and nitric oxide. 1169 87

We previously reported increased aortic reactive oxygen species (ROS) production in mineralocorticoid (deoxycorticosterone acetate [DOCA]-salt) hypertensive rats. In the present study, we tested the hypothesis that NADH/NADPH oxidase is responsible for increased ROS production, namely superoxide (O(2-)), in aorta from the DOCA-salt rat. Treatment of aortic rings from DOCA-salt rats with the NO synthase inhibitor N-nitro-L-arginine and the xanthine oxidase inhibitor allopurinol did not significantly change O(2-) production. Furthermore, de-endothelialization of aorta from DOCA-salt rats did not affect O(2-) production compared with that of sham-operated rats. Thus, xanthine oxidase and uncoupled endothelial NO synthase were not responsible for increased O(2-) production in the DOCA-salt rats. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased O(2-) production in aortic rings from DOCA-salt rats compared with sham-operated rats. Moreover, long-term administration of apocynin (in drinking water, 1.5 mmol/L, 28 days) to DOCA-salt rats significantly decreased systolic blood pressure compared with that of rats treated with DOCA-salt alone. Furthermore, O(2-) production in aortic rings from DOCA-salt rats treated with apocynin for 28 days was reduced compared with that of untreated DOCA-salt rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that DOCA-salt rats have significantly greater mRNA levels of the NADPH oxidase subunit p22phox than do sham-operated rats. These findings suggest that NADPH oxidase is increased and is responsible for increased O(2-) production and possibly contributes to increased blood pressure in the DOCA-salt hypertensive rat.
...
PMID:NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat. 1171 6

The production and role of reactive oxygen species (ROS) in the expanding zone of maize (Zea mays) leaf blades were investigated. ROS release along the leaf blade was evaluated by embedding intact seedlings in 2',7'-dichlorofluorescein-containing agar and examining the distribution of 2',7'-dichlorofluorescein fluorescence along leaf 4, which was exposed by removing the outer leaves before embedding the seedling. Fluorescence was high in the expanding region, becoming practically non-detectable beyond 65 mm from the ligule, indicating high ROS production in the expansion zone. Segments obtained from the elongation zone of leaf 4 were used to assess the role of ROS in leaf elongation. The distribution of cerium perhydroxide deposits in electron micrographs indicated hydrogen peroxide (H(2)O(2)) presence in the apoplast. 2',7'-Dichlorofluorescein fluorescence and apoplastic H(2)O(2) accumulation were inhibited with diphenyleneiodonium (DPI), which also inhibited O*(2)(-) generation, suggesting a flavin-containing enzyme activity such as NADPH oxidase was involved in ROS production. Segments from the elongation zone incubated in water grew 8% in 2 h. KI treatments, which scavenged H(2)O(2) but did not inhibit O*(2)(-) production, did not modify growth. DPI significantly inhibited segment elongation, and the addition of H(2)O(2) (50 or 500 microM) to the incubation medium partially reverted the inhibition caused by DPI. These results indicate that a certain concentration of H(2)O(2) is necessary for leaf elongation, but it could not be distinguished whether H(2)O(2), or other ROS, are the actual active agents.
...
PMID:Reactive oxygen species in the elongation zone of maize leaves are necessary for leaf extension. 1217 75

The roles of the plasma-membrane (PM) NADPH oxidase in abscisic acid (ABA)- and water stress-induced antioxidant defense were investigated in leaves of maize ( Zea mays L.) seedlings. Treatment by exogenous ABA (100 micro M ABA) or osmotic stress (-0.7 MPa induced by polyethylene glycol) significantly increased the activity of the PM NADPH oxidase, the production of leaf O(2)(-), the activities of several antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase), and the contents of antioxidant metabolites (ascorbate and reduced glutathione). Pretreatment with three different inhibitors of NADPH oxidase (diphenylene iodonium, imidazole and pyridine) or an inhibitor of ABA biosynthesis (tungstate) reduced the increase in the activity of the PM NADPH oxidase and the production of leaf O(2)(-), and the capacity of antioxidant defense systems mediated by ABA. The inhibitory effects above caused by tungstate were reversed by exogenous ABA. These data indicate that NADPH oxidase is involved in the ABA-induced production of active oxygen species (AOS), and our results depict a minimal chain of events initiated by water stress-induced ABA accumulation, which then triggers the production of AOS by membrane-bound NADPH oxidase, resulting in the induction of antioxidant defense systems against oxidative damage in plants.
...
PMID:Involvement of plasma-membrane NADPH oxidase in abscisic acid- and water stress-induced antioxidant defense in leaves of maize seedlings. 1235 63

Cell expansion is a central process in plant morphogenesis, and the elongation of roots and root hairs is essential for uptake of minerals and water from the soil. Ca2+ influx from the extracellular store is required for (and sets the rates of) cell elongation in roots. Arabidopsis thaliana rhd2 mutants are defective in Ca2+ uptake and consequently cell expansion is compromised--rhd2 mutants have short root hairs and stunted roots. To determine the regulation of Ca2+ acquisition in growing root cells we show here that RHD2 is an NADPH oxidase, a protein that transfers electrons from NADPH to an electron acceptor leading to the formation of reactive oxygen species (ROS). We show that ROS accumulate in growing wild-type (WT) root hairs but their levels are markedly decreased in rhd2 mutants. Blocking the activity of the NADPH oxidase with diphenylene iodonium (DPI) inhibits ROS formation and phenocopies Rhd2-. Treatment of rhd2 roots with ROS partly suppresses the mutant phenotype and stimulates the activity of plasma membrane hyperpolarization-activated Ca2+ channels, the predominant root Ca2+ acquisition system. This indicates that NADPH oxidases control development by making ROS that regulate plant cell expansion through the activation of Ca2+ channels.
...
PMID:Reactive oxygen species produced by NADPH oxidase regulate plant cell growth. 1266 Jul 86

Proton channels exist in a wide variety of membrane proteins where they transport protons rapidly and efficiently. Usually the proton pathway is formed mainly by water molecules present in the protein, but its function is regulated by titratable groups on critical amino acid residues in the pathway. All proton channels conduct protons by a hydrogen-bonded chain mechanism in which the proton hops from one water or titratable group to the next. Voltage-gated proton channels represent a specific subset of proton channels that have voltage- and time-dependent gating like other ion channels. However, they differ from most ion channels in their extraordinarily high selectivity, tiny conductance, strong temperature and deuterium isotope effects on conductance and gating kinetics, and insensitivity to block by steric occlusion. Gating of H(+) channels is regulated tightly by pH and voltage, ensuring that they open only when the electrochemical gradient is outward. Thus they function to extrude acid from cells. H(+) channels are expressed in many cells. During the respiratory burst in phagocytes, H(+) current compensates for electron extrusion by NADPH oxidase. Most evidence indicates that the H(+) channel is not part of the NADPH oxidase complex, but rather is a distinct and as yet unidentified molecule.
...
PMID:Voltage-gated proton channels and other proton transfer pathways. 1266 66

Metformin (dimethylbiguanide) is an antihyperglycemic agent used in type 2 diabetes. Beyond its action on glycemic control, metformin exhibits other intrinsic effects that could play a role in prevention against diabetes complications. Some studies thus reported an improvement in the antioxidant status in patients treated with metformin. This might be in part related to its property to limit formation of advanced glycation end products (AGEs) and to decrease the overproduction of free radicals in diabetic subjects. The aim of this study was to investigate the in vitro ability of metformin to modulate the action of reactive oxygen species (ROS) generated either by water gamma radiolysis or by stimulated human leukocytes. Our results showed that metformin at pharmacologically relevant concentrations was in vitro able to scavenge hydroxyl ((.)OH) but not superoxide (O(.-)(2)) free radicals and that hydrogen peroxide did not react with metformin. Nevertheless, when polymorphonuclear cells (PMN) are stimulated by phorbol myristate acetate (PMA), or above all by formyl methionine leucyl phenylalanine (fMLP), a systematic (although nonsignificant) decrease of the ROS-induced chimiluminescence (CL) was observed. These results suggest that metformin could directly scavenge ROS or indirectly act by modulating the intracellular production of superoxide anion, of which NADPH oxidase constitutes the major source. This could contribute to the additional benefits of metformin, especially those related to the improvement in the cardiovascular outcomes in diabetes.
...
PMID:An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress. 1275 88

We previously showed that hydrogen peroxide (H2O2) contributes to flow-induced dilation in human coronary resistance arteries (HCRAs); however, the source of this H2O2 is not known. We hypothesized that the H2O2 is derived from superoxide (O2*-) generated by mitochondrial respiration. HCRAs were dissected from right atrial appendages obtained from patients during cardiac surgery and cannulated with micropipettes. H2O2-derived radicals and O2*- were detected by electron spin resonance (ESR) using BMPO as the spin trap and by histofluorescence using hydroethidine (HE, 5 micromol/L) and dichlorodihydrofluorescein (DCFH, 5 micromol/L). Diameter changes to increases in pressure gradients (20 and 100 cm H2O) were examined in the absence and the presence of rotenone (1 micromol/L), myxothiazol (100 nmol/L), cyanide (1 micromol/L), mitochondrial complex I, III, and IV inhibitors, respectively, and apocynin (3 mmol/L), a NADPH oxidase inhibitor. At a pressure gradient of 100 cm H2O, ubisemiquinone and hydroxyl radicals were detected from effluents of vessels. Including superoxide dismutase and catalase in the perfusate reduced the ESR signals. Relative ethidium and DCFH fluorescence intensities in HCRAs exposed to flow were enhanced (1.45+/-0.15 and 1.57+/-0.12, respectively compared with no-flow) and were inhibited by rotenone (0.87+/-0.17 and 0.95+/-0.07). Videomicroscopic studies showed that rotenone and myxothiazol blocked flow-induced dilation (% max. dilation at 100 cm H2O: rotenone, 74+/-3% versus 3+/-13%; myxothiazol, 67+/-3% versus 28+/-4%; P<0.05). Neither cyanide nor apocynin altered flow-induced dilation. These results suggest that shear stress induced H2O2 formation, and flow-induced dilation is derived from O2*- originating from mitochondrial respiration.
...
PMID:Mitochondrial sources of H2O2 generation play a key role in flow-mediated dilation in human coronary resistance arteries. 1291 51

Voltage gated proton channels were first discovered in snail neurons and recently have been found in many mammalian cells. As their name suggests, H+ channels are sensitive to voltage, with an open probability that increases with membrane depolarization. Many properties that are shared by voltage-gated proton channels make them unique among ion channels. They show high selectivity for protons, strongly pH dependent gating, and a tiny single channel conductance. Although they are inhibited by divalent cations, including zinc and cadmium, no effective blockers exist. There is sufficient evidence to suggest that they are not water filled pores, unlike many other membrane bound ion channels. Instead, protons probably are conducted by a "hydrogen bonded chain" mechanism that resembles the Grotthuss mechanism in water. Differences in activation and deactivation kinetics of H+ currents in different cells suggest that there may be at least 4 isoforms of voltage gated proton channels. Gating kinetics may reflect specific functions. Voltage gated proton channels are well suited to extrude acid from cells and also may function in the extrusion of metabolic acid in the form of CO2 from the lungs. The best established function of H+ channels is in mammalian phagocytes, where they extrude protons to compensate for the charge separation created by the movement of electrons across the membrane by the bactericidal enzyme NADPH oxidase.
...
PMID:Diversity of voltage gated proton channels. 1295 41

Vasopressin regulates water and solute transport in the renal collecting duct. In addition to short-term regulation of aquaporin-2 trafficking, vasopressin also has long-term effects to regulate the abundances of aquaporins-2 and -3 and beta- and gamma-subunits of the epithelial sodium channel in collecting duct principal cells. To investigate further the direct and indirect long-term regulatory actions of vasopressin in the inner medullary collecting duct (IMCD), we used a proteomic approach [difference gel electrophoresis (DIGE) coupled with MALDI-TOF identification of differentially expressed protein spots]. DDAVP or vehicle was infused subcutaneously in Brattleboro rats for 3 days, and IMCD cells were purified from the inner medullas for proteomic analysis. Forty-three proteins were found to be regulated in response to vasopressin infusion, including 18 that were increased in abundance, 22 that were decreased, and 3 that were shifted in the gel, presumably because of posttranslational modification. Immunocytochemistry confirmed collecting duct expression of several of the proteins that were identified. Immunoblot analysis of nine of the proteins confirmed the changes seen by the DIGE method. Of these nine proteins, six were increased in response to DDAVP infusion: nitric oxide synthase-2 (NOS2), GRP78, heat shock protein-70, annexin II, glutaminase, and cathepsin D. The remaining three were decreased in response to DDAVP: aldehyde reductase I, adenylyl cyclase VI, and carbonic anhydrase II. The findings point to a role for vasopressin in the coordinate regulation of several determinants of nitric oxide levels (NOS2, arginase II, NADPH oxidase) and of proteins potentially involved in vasopressin escape (adenylyl cyclase VI and G protein-coupled receptor kinase 4).
...
PMID:Proteomic analysis of long-term vasopressin action in the inner medullary collecting duct of the Brattleboro rat. 1453 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---