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)

Different agents such as phorbol myristate acetate (PMA), N-formyl-methionyl-leucylphenylalanine (fMet-Leu-Phe), or opsonized zymosan induced an oxidative burst in rat peritoneal polymorphonuclear leukocytes (PMNs) elicited by casein. Plastic adhesion of PMNs down-regulated superoxide (O2) release stimulated by PMA or fMet-Leu-Phe but had no effect on zymosan-induced O2 generation, indicating that the O2 forming enzyme, the NADPH oxidase, was not affected by modulation and that a common step of the transductional events induced by PMA or fMet-Leu-Phe might be involved in this regulation. We demonstrated that a differential translocation of protein kinase C (PKC) was not responsible for that modulation. PMA-induced secretion of granule content (vitamin B12-binding protein) was not susceptible to modulation, suggesting that the transductional pathways leading to O2 generation and granule secretion are partly separated. The adhesion of PMNs to different substrates (glass, plastic, albumin-, laminin-, fibronectin-, poly-lysine-, or concanavalin A-coated plastic) down-regulated to different extent superoxide release. Whether the nature of the biochemical signal induced by the diverse adhesive stimuli or a physical parameter such as binding strength was involved in this differential behavior remains to be elucidated. Since adhesiveness was dependent on the state of the cytoskeleton and O2 inducers were reported to stimulate actin polymerization, we studied the F-actin content and distribution of PMNs by using the specific fluorescent probe NBD-phallacidin and an original methodology allowing a quantitative analysis of fluorescence on both adherent and suspended cells. PMA induced a polarization of F-actin on suspended PMNs but had no effect on the intracellular distribution of F-actin in adherent PMNs. Thus, we suggest that the adhesion of PMNs induced an immobilization of F-actin, possibly correlated to the down-regulation of one of the transductional pathways involved in the NADPH oxidase activation.
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PMID:Oxidative metabolism of polymorphonuclear leukocytes: modulation by adhesive stimuli. 184 13

The protein kinase C inhibitor staurosporine influenced in different ways the functions of human neutrophils. Staurosporine prevented the enhanced protein phosphorylation in phorbol ester- and N-formylmethyionyl-leucylphenylalanine (fMLP)-stimulated cells, and was a powerful inhibitor of the respiratory burst induced by phorbol myristate acetate [IC50 (concentration causing 50% inhibition) 17 nM] and the chemotactic peptides fMLP and C5a (IC50 24 nM). It did not alter, however, the superoxide production by cell-free preparations of NADPH oxidase. Staurosporine had no effect on agonist-dependent changes in cytosolic free Ca2+ and exocytosis of specific and azurophil granules, and showed only a slight inhibition of the release of vitamin B12-binding protein induced by phorbol myristate acetate (decreased by 40% at 200 nM). On the other hand, staurosporine also exhibited neutrophil-activating properties: it induced the release of gelatinase (from secretory vesicles) and vitamin-B12-binding protein (from specific granules). These effects were protracted, concentration-dependent, insensitive to Ca2+ depletion, and strongly enhanced by cytochalasin B. Staurosporine, however, did not induce the release of beta-glucuronidase or elastase (from azurophil granules). Except for the sensitivity to cytochalasin B, these properties suggest a similarity between the exocytosis-inducing actions of staurosporine and PMA. The results obtained with staurosporine provide further evidence that different signal-transduction processes are involved in neutrophil activation, and suggest that protein phosphorylation is required for the induction of the respiratory burst, but not for exocytosis.
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PMID:Staurosporine inhibits the respiratory burst and induces exocytosis in human neutrophils. 255 21

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.
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PMID:Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period. 1671 19

Oxidative stress is commonly observed in the elderly and could be involved in age-related diseases. However, the determinants of superoxide anion overproduction are not clearly understood. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method in 478 elderly subjects (304 women, 174 men; 79.5+/-7.1 years). Homocysteine (HCy) metabolism (homocysteinemia, vitamin B12, plasma, and erythrocyte folates), inflammation (CRP, fibrinogen, alpha-1 acid glycoprotein), lipid parameters (total cholesterol, triglycerides, HDL and LDL cholesterol), and nutritional parameters (albumin, transthyretin) were determined. The results show that HCy levels (p<0.001) and superoxide anion production (p=0.04) increase with aging, but CRP does not. Highest HCy (>20 microM) (OR 1.83 (1.09-3.07), p=0.02) and CRP over 5 mg/L (adjusted OR 2.01 (1.15-3.51), p=0.01) are the main determinants in superoxide anion production in the elderly. These clinical data are confirmed in an in vitro study using THP-1 monocyte-like cells. Incubation with HCy thiolactone (HTL) (0-200 microM) and LPS (0-20 ng/ml) dramatically enhances NADPH oxidase expression and activation. Moreover, a synergic action was evidenced for low concentrations of HTL (20 microM) and LPS (5 ng). Taken together, the clinical data and in vitro experiments support the hypothesis that moderate homocysteinemia and low-grade inflammation synergically enhance NADPH oxidase activity in the elderly.
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PMID:Homocysteine and inflammation as main determinants of oxidative stress in the elderly. 1908 60