Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is a short-lived, diffusible molecule that has a variety of biological activities including vasorelaxation, neurotransmission, and cytotoxicity. In the central nervous system, a constitutive form of nitric oxide synthase (NOS) has been localized in a subset of neurons and in endothelial cells. In addition, both constitutive and LPS-inducible NOS has been demonstrated in rat astrocytes and microglia in vitro. In this report, we present evidence for the production of NO, as measured by the production of nitrite, in highly enriched human fetal astrocyte cultures stimulated with IL-1 beta. The production of nitrite paralleled the induction of NADPH diaphorase enzyme activity in the perikarya of the majority of stimulated astrocytes. The IL-1 beta-induced nitrite production by astrocytes was markedly enhanced when cells were co-stimulated with IFN-gamma or TNF-alpha (IFN-gamma > TNF-alpha); LPS had no effect used as a single agent or in combination with other cytokines. NGMMA and NG-nitro-arginine, competitive inhibitors of NOS, diminished the accumulation of nitrite, but calmodulin antagonists (trifluoperazine, W-5 and W-7) had little or no inhibitory effect. Human fetal microglia, in contrast to astrocytes, failed to secrete significant amounts of nitrite in response to various stimuli. The results demonstrate the presence of an inducible form of NOS in human fetal astrocytes; human microglia, in turn, may control astrocyte NO production by providing IL-1 beta as an activating signal.
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PMID:Induction of nitric oxide synthase activity in human astrocytes by interleukin-1 beta and interferon-gamma. 768 87

Injection of an Ascaris suum extract (Asc) affects both the humoral and cellular immune responses to unrelated antigens when it is co-administered with these antigens. In the present study we evaluated the effect of Asc on macrophage activation in the early phase of Mycobacterium bovis BCG (Pasteur strain TMCC 1173) infection in C57Bl/6 mice. C57Bl/6 mice were injected intraperitoneally (ip) with 0.1 mg BCG (BCG group) or BCG plus 1 mg Asc (BCG + Asc group). The peritoneal exudates were obtained at 2, 7 and 14 days after infection. The numbers of IFN-gamma-secreting cells were assessed by the ELISPOT assay. Nitric oxide (NO) production was measured by the Griess method and by the evaluation of NADPH diaphorase activity in the peritoneal exudates. The administration of Asc extract increased NADPH diaphorase activity (2 days: control = 0, BCG = 7%, BCG + Asc = 13%, and Asc = 4%; 7 days: control = 4, BCG = 13%, BCG + Asc = 21%, and Asc = 4.5%) and TNF-alpha levels (mean +/- SD; 2 days: control = 0, BCG = 169 +/- 13, BCG + Asc = 202 +/- 37, and Asc = 0; 7 days: control = 0, BCG = 545 +/- 15.5, BCG + Asc = 2206 +/- 160.6, and Asc = 126 +/- 26; 14 days: control = 10 +/- 1.45, BCG = 9 +/- 1.15, BCG + Asc = 126 +/- 18, and Asc = 880 +/- 47.67 pg/ml) in the early phase of BCG infection. Low levels of NO production were detected at 2 and 7 days after BCG infection, increasing at 14 days (mean +/- SD; 2 days: control = 0, BCG = 3.7 +/- 1.59, BCG + Asc = 0.82 +/- 0.005, Asc = 0.48 +/- 0.33; 7 days: control = 0, BCG = 2.78 +/- 1.54, BCG + Asc = 3.07 +/- 1.05, Asc = 0; 14 days: control = 0, BCG = 9.05 +/- 0.53, BCG + Asc = 9.61 +/- 0.81, Asc = 10.5 +/- 0.2 (2 x 10(6)) cells/ml). Furthermore, we also observed that Asc co-injection induced a decrease of BCG-colony-forming units (CFU) in the spleens of BCG-infected mice during the first week of infection (mean +/- SD; 2 days: BCG = 1.13 +/- 0.07 and BCG + Asc = 0.798 +/- 0.305; 7 days: BCG = 1.375 +/- 0. 194 and BCG + Asc = 0.548 +/- 0.0226; 14 days: BCG = 0.473 +/- 0.184 and BCG + Asc = 0.675 +/- 0.065 (x 10(2)) CFU). The present data suggest that Asc induces the enhancement of the immune response in the early phase of BCG infection.
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PMID:Effect of the injection of an extract of Ascaris suum on macrophage activation during the early phase of Mycobacterium bovis BCG infection in C57Bl/6 mice. 1055 45

Nitric oxide (NO) can play an important role in the regulation of vascular tone and neurotransmission, as well as in non-specific immunoreactions and inflammation in a variety of tissues. Increased quantities of nitric oxide in respired air can be measured during inflammatory processes. However, the exact role and precise sources of NO under physiological and pathophysiological conditions within the airways remain to be defined. Three isoforms of NO-synthases can be distinguished: two constitutive (neuronal and endothelial) Ca(2+)-dependent cNOS and one inducible Ca(2+)-independent iNOS (NOS II). Constitutive NOS (NOS I and III) release a basal amount of NO under physiological conditions. The inducible form once expressed can catalyse the generation of large quantities of NO. Many kinds of cells, such as macrophages, neutrophils, endothelium and smooth muscle cells, are capable of expressing NOS II. Since all isoforms of NO-synthase seem to be present in nasal tissues and the expression of iNOS under inflammatory conditions seems to be responsible for excessive production of NO, the distribution of NOS-isoforms (especially NOS II) in normal and inflammatory nasal tissue, as well as the exact requirements for expression of iNOS remain to be proven. Non-inflamed fresh human nasal mucosa from the middle turbinate was compared immuno-histologically with nasal mucosa having the typical findings of chronic polypoid rhinosinusitis (i.e., polypoid middle turbinates and polyps of the middle nasal duct). In order to gain more information about the mechanisms of acute inflammation, non-inflamed vital turbinates were incubated in vitro with the proinflammatory substances bacterial lipopolysaccharides (LPS) and tumor necrosis-factor (TNF) for 30, 60, 90, 120, 180 and 240 min. Subsequent to exposure to NADPH-diaphorase and immunostaining with specific antibodies to each NOS-isoform, clearly increased or initiated expressions of inducible NOS (iNOS) in blood vessels, glands, macrophages and epithelium of chronically inflamed and LPS-incubated nasal tissue became apparent in comparison to the non-inflamed controls. In contrast, NOS III/NOS I seemed to be not affected. The onset of immunohistochemically recognizable NOS II expression was observed after 90 min incubation with of LPS/TNF-alpha. Polypoid tissue showed a strong increase in submucosal thickness and a high infiltration of iNOS-positive leukocytes (granulocytes and macrophages) compared to the LPS-incubated non-inflamed specimens. These findings implicate NOS II generated nitric oxide as a key agent for causing swelling, secretion and obstruction in patients with acute and chronic polypoid or allergic rhinitis. These findings also suggest that molecular NO has to be considered in the pathophysiology of chronic polypoid rhinosinusitis.
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PMID:[Detection of nitric oxide synthases in physiological and pathophysiological processes of the nasal mucosa]. 1095 25