Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.19 (NOS)
 7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently isolated trophoblasts express nitric oxide synthase 2 (NOS-2) and cyclooxygenase 2 (COX-2), decreasing the levels of the corresponding mRNAs when the cells were maintained in culture. The sustained expression of COX-2 and NOS-2 in trophoblasts was dependent on the activation of nuclear factor kappaB (NF-kappaB) since proteasome inhibitors and antioxidants that abrogated NF-kappaB activity suppressed the induction of both genes. The time-dependent fall of the mRNA levels of NOS-2 and COX-2 paralleled the inhibition of NF-kappaB, determined by electrophoretic mobility shift assays, and the increase of the IkappaBalpha and IkappaBbeta inhibitory proteins. Isolated trophoblasts synthesized reactive oxygen intermediates (ROI), a process impaired after culturing the cells, and that might be involved in the NF-kappaB activation process. Moreover, treatment of recently isolated cells with ROI scavengers suppressed the expression of COX-2 and NOS-2. Challenge of trophoblasts with interleukin-1beta up-regulated the expression of both proteins, an effect that was potentiated by lipopolysaccharide. These results indicate that the physiological expression of NOS-2 and COX-2 in trophoblasts involves a sustained activation of NF-kappaB which inhibition abrogates the inducibility of both genes.
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PMID:Requirement of nuclear factor kappaB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts. 1046 30

In brain astrocytes, nuclear factor kappaB (NF-kappaB) is activated by stimuli that produce cellular stress causing the expression of genes involved in defence, including the inducible nitric oxide synthase (NOS-2). Theiler's murine encephalomyelitis virus (TMEV) induces a persistent CNS infection and chronic immune-mediated demyelination, similar to human multiple sclerosis. The cytokines interleukin (IL)-4 and IL-10 inhibit the expression of proinflammatory cytokines, counteracting the inflammatory process. Our study reports that infection of cultured astrocytes with TMEV resulted in a time-dependent phosphorylation of IkappaBalpha, degradation of IkappaBalpha and IkappaBbeta, activation of NF-kappaB and expression of NOS-2. The proteasome inhibitor MG-132 blocked TMEV-induced nitrite accumulation, NOS-2 mRNA expression and phospho-IkappaBalpha degradation, suggesting NF-kappaB-dependent NOS-2 expression. Pretreatment of astrocytes with IL-4 or IL-10 decreased p65 nuclear translocation, NF-kappaB binding activity and NOS-2 transcription. IL-4 and IL-10 caused an accumulation of IkappaBalpha in TMEV-infected astrocytes without affecting IkappaBbeta levels. The IkappaB kinase activity and the degradation rate of both IkappaBs were not modified by either cytokine, suggesting de novo synthesis of IkappaBalpha. Indeed, IL-4 or IL-10 up-regulated IkappaBalpha mRNA levels after TMEV infection. Therefore, the accumulation of IkappaBalpha might impair the translocation of the NF-kappaB to the nucleus, mediating the inhibition of NF-kappaB activity. Overall, these data suggest a novel mechanism of action of IL-4 and IL-10, which abrogates NOS-2 expression in viral-infected glial cells.
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PMID:Interleukin-4 and interleukin-10 modulate nuclear factor kappaB activity and nitric oxide synthase-2 expression in Theiler's virus-infected brain astrocytes. 1206 72

The ability of neonatal and adult cardiomyocytes to activate the nuclear factor (NF)-kappaB pathway in response to lipopolysaccharide and interleukin-1beta challenge has been investigated and compared with that of peritoneal macrophages. The activation of the IkappaB kinase and the phosphorylation and degradation of IkappaBalpha and IkappaBbeta was much lower in adult cardiomyocytes than in the neonatal counterparts and macrophages. This restricted activation of the NF-kappaB pathway resulted in a significant reduction in the time of nuclear activation of NF-kappaB, as deduced by electrophoretic mobility shift assays and in the transcription of target genes, such as IkappaBalpha, cyclooxygenase-2 (COX-2) and nitric-oxide synthase-2 (NOS-2). Studies on chromatin immunoprecipitation showed binding of NF-kappaB proteins to the regulatory kappaB sites identified in the promoters of the IkappaBalpha, COX-2, and NOS-2 genes in macrophages and, to a lower extent, in neonatal cardiomyocytes. The binding to these kappaB sites in adult cardiomyocytes was observed only in the IkappaBalpha promoter and was minimal or absent in the COX-2 and NOS-2 promoters, respectively, suggesting a restricted activation of NF-kappaB-regulated genes in these cells. These data indicate that the function of the NF-kappaB pathway in adult cardiomyocytes is limited in time, which results in the expression of a reduced number of genes and provides a functional explanation for the absence of NOS-2 inducibility in these cells under proinflammatory conditions.
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PMID:Selective impairment of nuclear factor-kappaB-dependent gene transcription in adult cardiomyocytes: relevance for the regulation of the inflammatory response in the heart. 1767 83

Although dam mutants of Salmonella have been proposed as live vaccines, their capacity to trigger cell inflammatory cascades has not been fully elucidated. We investigated in detail the ability of Salmonella enterica dam mutant to activate the signalling pathways of the inflammatory response in RAW 264.7 cells. Apoptosis in macrophages treated with Salmonella dam mutant was low. Similarly, the expression of both NOS-2 and COX-2 and subsequently the production of NO and PGE(2) was significantly reduced. Also, Salmonella dam mutant induced an attenuated activation of the inflammatory signalling pathway as indicated by the reduced degradation of IkappaBalpha and IkappaBbeta and the low IkappaBalpha phosphorylation found. In addition, translocation of p65 to the nucleus was notably impaired and the amount of phosphorylated p44, p42 and p38 MAPKs was clearly reduced in extracts from dam-infected macrophages. These results indicate that the lack of ERK and p38 phosphorylation at the proper time in dam-infected cells notably reduces the engagement of subsequent signalling pathways involved in the full activation of NF-kappaB in response to infection. Taken together, these results suggest that Salmonella activation of both signalling cascades in the inflammatory response is a mechanism requiring Dam protein participation.
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PMID:Salmonella enterica serovar Enteritidis dam mutant induces low NOS-2 and COX-2 expression in macrophages via attenuation of MAPK and NF-kappaB pathways. 1880 55