Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) regulates cellular function, in part, by S-nitrosylating active site thiol groups of proteins. Ex vivo S-nitrosylation of NF-kappa B p50 significantly decreases its capacity for DNA binding. To determine the cellular relevance of this observation, we utilized the ANA-l murine macrophage model of endotoxin (LPS)-mediated NO synthesis. In selected instances, the NO synthase inhibitor, L-arginine methyl ester (L-NAME; 100 microM), or the NO donor, S-nitroso-N-acetylcysteine (SNAC; 100 microM), was added. In contrast to that of LPS cells, nuclear extracts from LPS + L-NAME cells demonstrated increased NF-kappa B DNA binding on gel shift analysis. Addition of SNAC to LPS + L-NAME cells restored binding to a level equivalent to that of LPS cells. Spectrophotometric analysis of NF-kappa B p50 immunoprecipitates demonstrated S-NO bonds exclusively in LPS cells; these p50 protein isolates retained the same DNA binding characteristics as that of the nuclear extracts. Transfection assays utilizing NF-kappa B-dependent promoter-reporter constructs demonstrated increased activity in LPS + L-NAME cells compared with LPS cells; nuclear run-on assays confirmed increased transcription of the corresponding genes. These results suggest that LPS-mediated NO synthesis is associated with S-nitrosylation of NF-kappa B p50 and inhibition of NF-kappa B-dependent DNA binding, promoter activity, and gene transcription. We conclude that NO can regulate gene transcription by S-nitrosylation of NF-kappa B.
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PMID:Endotoxin-mediated S-nitrosylation of p50 alters NF-kappa B-dependent gene transcription in ANA-1 murine macrophages. 1020 34

We tested the hypothesis that NO synthase inhibition alters proinflammatory cytokine expression during acute lung injury in mice. Five-week-old CD-1 mice were pretreated with l-NAME or d-NAME and then received an intratracheal injection of endotoxin (or PBS). TNF-alpha and IL-6 ELISAs and RT-PCR were performed on lung homogenates sampled 6 h later. l-NAME increased TNF-alpha and IL-6 protein and mRNA expression in lungs. Immunostaining demonstrated that TNF-alpha was expressed predominantly by macrophages in the lung. l-NAME did not alter pulmonary macrophage concentration. To better understand the effect of NO synthase inhibition, elicited murine peritoneal macrophages were stimulated in vitro with LPS after addition of l-NAME, d-NAME, nitroprusside, or control. Nuclear proteins were extracted 3 h later and electrophoretic mobility shift and supershift assays were performed using radiolabeled NF-kappaB consensus sequence oligonucleotides. Endotoxin increased NF-kappaB p50/p65 heterodimer binding. Binding was further increased by l-NAME and decreased by nitroprusside. The effect of nitroprusside was not blocked by guanylate cyclase inhibition. We conclude that, in endotoxin-induced acute lung injury, NO synthase inhibition increases proinflammatory cytokine protein and mRNA expression in part because NO decreases the amount of NF-kappaB available for binding to the regulatory region of proinflammatory cytokine genes.
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PMID:Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. 1043 Jul 48

Oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis. Inflammatory genes including inducible nitric oxide synthase (iNOS) may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-kappaB on iNOS expression and apoptosis in H. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC), iNOS inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite donor SIN-1, and a nitric oxide donor NOC-18 in the presence or absence of H. pylori. H. pylori induced cytotocixity time- and dose-dependently, which occurred with induction in iNOS expression and nitrite production. SIN-1 and NOC-18 induced dose-dependent cytotoxicity in AGS cells. Catalase, PDTC, L-NAME, and AMT prevented H. pylori-induced cytotoxicity and apoptosis. It was related to their inhibition on iNOS expression and nitrite production. The cells treated with AS ODN had low levels of p50 and NF-kappaB and inhibited H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-kappaB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells.
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PMID:NF-kappaB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection. 1146 73

Nuclear factor kappa B (NFkappaB), commonly a proinflammatory transcription factor, is responsible for increasing transcription of the endothelial cell nitric oxide synthase (eNOS) in response to laminar shear stress. Nitric oxide (NO) production can be stimulated by shear, and NO is known to inhibit NFkappaB activation. We hypothesized that this inhibitory action of NO on NFkappaB activation serves as a negative feedback to inhibit NFkappaB activity and eNOS transcription. Exposure of bovine aortic endothelial cells to laminar shear stimulated steady state eNOS mRNA expression and eNOS promoter activity as measured using an eNOS promoter/CAT construct. These effects of shear were enhanced by the NOS inhibitor l-NAME and decreased by the NO-donor DPTA-NO by 30-50%. The NFkappaB inhibitor panepoxydone prevented the increase in eNOS mRNA caused by shear confirming a role of NFkappaB in this response. Shear stress stimulated a transient (30 min) nuclear translocation of the NFkappaB subunit p50. Treatment with l-NAME increased binding of the NFkappaB subunit p50 to consensus oligonucleotide-coated microtiter plates, while having only minimal effect on binding of p65, strongly suggesting that nitric oxide mainly inhibits p50 activation. Using the biotin switch method, we found that shear stress stimulates p50 nitrosylation and this was prevented by l-NAME. Moreover, transfection of endothelial cells with a vector encoding the C62S p50, a variant with a point mutation of the nitrosylation site C62, markedly increased nuclear translocation of p50 and doubled eNOS mRNA expression under shear stress compared to that observed in cells transfected with wild-type p50. We conclude that this interaction between shear, NFkappaB activation, NO production and NFkappaB inhibition represents a classical negative feedback loop, which prevents sustained activation of NFkappaB. In the absence of NO, shear stimulation of NFkappaB and eNOS transcription are enhanced. Our findings emphasize the critical role of NO in modulation of the endothelial cell inflammatory state. Several common diseases, including hypercholesteremia, hypertension and diabetes, are associated with eNOS dysfunction. Under these conditions, decreased NO availability may result in sustained activation of NFkappaB in response to shear and unrestrained endothelial inflammation.
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PMID:A negative feedback mechanism involving nitric oxide and nuclear factor kappa-B modulates endothelial nitric oxide synthase transcription. 1609 68

NF-kappaB is a versatile transcription factor that regulates a wide array of processes, including inflammation and survival, and plays a critical role in the etiology of inflammatory lung diseases. Nitric oxide (NO) has been suggested to play an antiinflammatory role through S-nitrosation of components of NF-kappaB pathway. NO production can be modulated by changing the availability of its substrate, L-arginine. Arginases compete with NO synthases (NOSs) for their common substrate, L-arginine, and thereby have the potential to alter the signaling function of NO. The goal of the present study was to determine the impact of arginase manipulation on NO, and subsequent effects on NF-kappaB activation, in lung epithelial cells. Our results demonstrate that reduction of arginase activity enhanced cellular content of NO and S-nitrosated proteins, and resulted in decreases in TNF-alpha- or LPS-stimulated NF-kappaB DNA binding and transcriptional activity, in association with enhanced S-nitrosation of p50. The effects of arginase inhibition on NF-kappaB were reversed by the generic NOS inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), suggesting a causal role for NO in the attenuation of NF-kappaB induced by arginase suppression. Conversely, overexpression of arginase I decreased cellular S-nitrosothiol content and enhanced IkappaB kinase activity and NF-kappaB DNA binding, and decreased S-nitrosation of p50. Collectively, our data point to a regulatory mechanism wherein NF-kappaB is controlled through arginase-dependent regulation of NO levels, which may impact on chronic inflammatory diseases that are accompanied by NF-kappaB activation and upregulation of arginases.
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PMID:Oxidative-nitrosative stress and post-translational protein modifications: implications to lung structure-function relations. Arginase modulates NF-kappaB activity via a nitric oxide-dependent mechanism. 1721 16

Gaseous transmitters contribution in blood oxygen transport function modification under the influence of the magnetic field was studied. It is found, that irradiation of the tail artery of rats for 10 days during 10 minutes increases p50 value, indicating a decrease in the hemoglobin affinity for oxygen and is accompanied by increased concentrations of nitrate/nitrite, and hydrogen sulfide. Administration of L-arginine and nitroglycerin during magnetic field action is accompanied by a decrease of hemoglobin affinity for oxygen, which is absent when NO-synthase enzyme inhibitor (L-NAME) is added. These data suggest an important role in the formation of blood oxygen transport function such gaseous transmitters as nitrogen monoxide and hydrogen sulfide.
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PMID:[PARTICIPATION OF GASEOUS TRANSMITTERS IN BLOOD OXYGEN TRANSPORT FUNCTION MODIFICATION UNDER THE INFLUENCE OF MAGNETIC FIELD]. 3019 35