Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The magnitude and duration of the abruptly occurring increases in cytosolic Ca2+ in human neutrophils following activation with PAF (20 and 200 nM) and FMLP (1 microM), have been compared and related to alterations in NADPH oxidase activity, membrane potential and intracellular cyclic AMP. Cytosolic Ca2+ and membrane potential were measured by spectrofluorimetry, transmembrane fluxes of Ca2+ by radiometric procedures, and NADPH oxidase activity and cyclic AMP by chemiluminescence and radioimmunoassay respectively. Activation of neutrophils with both PAF (200 nM) and FMLP (1 microM) was accompanied by an abrupt increase in cytosolic Ca2+, which was of similar magnitude for each activator (393+/-9 and 378+/-17 nM respectively). Unlike FMLP-activated cells in which Ca2+ was rapidly removed from the cytosol, peak levels of cytosolic Ca2+ were sustained for longer (0.14+/-0.02 vs 1.16+/-0.04 min, P<or=0.0001) and declined at a slower rate in PAF-treated neutrophils. The prolonged elevation of cytosolic Ca2+ in PAF-treated cells was due to accelerated store-operated influx of extracellular cation and was attenuated by dibutyryl cyclic AMP (4 mM), the Ca2+-chelator, EGTA (5 mM), and SKF 96365 (10 microM). In contrast to FMLP, basal levels of superoxide production and cyclic AMP were unaltered in PAF-activated neutrophils, while only moderate membrane depolarization was detected. These observations demonstrate that mechanisms which restore Ca2+ homeostasis to FMLP-activated neutrophils, viz. activation of NADPH oxidase and adenylate cyclase, are not operative in PAF-treated cells, presenting the potential hazard of Ca2+ overload and hyperactivity.
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PMID:Dissociation of the PAF-receptor from NADPH oxidase and adenylate cyclase in human neutrophils results in accelerated influx and delayed clearance of cytosolic calcium. 1197 71

Activation of the NADPH oxidase system to generate reactive oxygen species (ROS) plays a key role in bacterial killing by human neutrophils. However, the involvement of such radicals in spontaneous and TNFalpha-driven neutrophil apoptosis remains uncertain. While incubation of cells under anoxic conditions attenuated the pro-apoptotic effect of TNFalpha, full activation of the respiratory burst using PAF followed by fMLP, or the addition of physiologically relevant concentrations of H(2)O(2), had no effect on the rate of apoptosis. Furthermore, the phosphoinositide 3-kinase inhibitor, LY294002, which abolishes receptor-mediated activation of the NADPH oxidase, and five discrete anti-oxidants all failed to affect apoptotic thresholds. Thus ROS do not appear to modulate constitutive apoptosis in neutrophils or appear sufficient to mediate the pro-apoptotic effect of TNFalpha.
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PMID:Hypoxic regulation of neutrophil apoptosis role: of reactive oxygen intermediates in constitutive and tumor necrosis factor alpha-induced cell death. 1503 62

The tonic contraction of human and guinea pig gallbladder (GB) is dependent on basal levels of PGE(2) and thromboxane A(2) (TxA(2)). The pathway involved in the genesis of these prostaglandins has not been elucidated. We aimed to examine the source of reactive oxygen species (ROS) and whether they contribute to the genesis of GB tonic contraction by generating basal prostaglandin levels. Tonic contraction was studied in human and guinea pig GB muscle strips treated with ROS scavengers (Tiron and catalase), apocynin (an inhibitor of NADPH oxidase), and NOX-1 small interference RNA (siRNA). The subunits of NADPH oxidase and their functional roles were determined with specific antibodies in GB muscle cells. ROS scavengers reduced the GB tonic contraction and H(2)O(2) and PGE(2) levels. Apocynin also inhibited the tonic contraction. Antibodies against subunits of NADPH oxidase present in GB muscle cells lowered H(2)O(2) and PGE(2) levels. NOX-1 siRNA transfection reduced the tonic contraction, NOX-1 expression, and levels of H(2)O(2) and PGE(2). Tiron and apocynin inhibited the expected increase in tension and H(2)O(2) levels induced by stretching of muscle strips. H(2)O(2) increased the levels of PGE(2) and TxA(2) by increasing platelet-activating factor-like lipids that phosphorylate p38 and cPLA(2) sequentially. H(2)O(2) generated by NADPH oxidase participates in a signal transduction pathway that maintains the GB tonic contraction by activating PAF, p38, and cPLA(2) to generate prostaglandins.
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PMID:Reactive oxygen species are messengers in maintenance of human and guinea pig gallbladder tonic contraction. 1862 97