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)

Peroxynitrite, formed by nitric oxide (NO) and superoxide, can alter protein function by nitrating amino acids such as tyrosine, cysteine, trytophan, or methionine. Inducible nitric oxide synthase (Type 2 NOS or iNOS) converts arginine to citrulline, releasing NO. We hypothesized that peroxynitrite could function as a negative feedback modulator of NO production by nitration of iNOS. Confluent cultures of the murine lung epithelial cell line, LA-4 were stimulated with cytokines to express iNOS, peroxynitrite was added, and the flasks sealed. After 3 h, NO in the headspace above the culture was sampled. Peroxynitrite caused a concentration-dependent decrease in NO. Similar results were obtained when 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, was added to the flasks. PAPA-NONOate, the NO generator, did not affect the headspace NO. Nitration of the iNOS was confirmed by detection of 3-nitrotyrosine by Western blotting. These data suggest a mechanism for inhibition of NO synthesis at inflammatory sites where iNOS, NO, and superoxide would be expected.
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PMID:Peroxynitrite inhibits inducible (type 2) nitric oxide synthase in murine lung epithelial cells in vitro. 1131 78

A possible role of nitric oxide (NO) on adipocyte lipolysis was studied in exercise-trained (9 weeks of running) rats. Lipolysis in adipose tissue tended to be greater in trained rats than in control rats. A treatment of adipose tissue with 5 mM N(G)-nitro-L-arginine methyl ester (L-NAME) showed that basal and isoproterenol-stimulated lipolysis were both significantly greater in trained rats than in control rats. In contrast, in isolated adipocytes L-NAME had no effect on lipolysis in either group of rats, though the lipolysis of isolated adipocytes was significantly greater in trained rats than in control rats. Training significantly reduced nitrite/nitrate production in adipocytes, but not in tissue. On the other hand, training increased the protein expression of endothelial nitric oxide synthase (eNOS), but not that of inducible NOS (iNOS) in the extracts of tissue homogenates. In tissue homogenates, eNOS activity but not iNOS activity was significantly greater in trained rats than in control rats. In cellular extracts, training significantly reduced the activities of both NOS's, but the mRNA expressions of both NOS's were not different between groups. The NO donors, S-nitroso-N-acetyl-penicillamine (SNAP) and 1-propamine, 3-(2-hydroxy-2-nitroso-1-propyl-hydrazine) (PAPA-NONOate), significantly inhibited adipocyte lipolysis in response to isoproterenol in both groups. This inhibitory effect of SNAP, but not that of PAPA-NONOate, was greater in the adipocytes of trained rats than in those of the control rats. Thus it is possible that NO is involved in the regulation of lipolysis and that exercise training enhances the responsiveness of adipocytes to extracellular NO with the reduced production of nitrite/nitrate in adipocytes because of decreased activities of NOS's. On the other hand, it is also possible that exercise increases either the activity or the protein expression of eNOS in adipose tissue.
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PMID:Possible role of nitric oxide on adipocyte lipolysis in exercise-trained rats. 1251 69

We hypothesized that targeted mutation of the endothelial nitric oxide synthase (eNOS) gene would reduce Akt-related signaling events in skeletal muscle cells, compared to wild type (WT) controls. Results show that slow myosin heavy chain (type I/beta) expression and the abundance of slow-twitch fibers are reduced in plantaris muscle of eNOS(-/-) mice, compared to WT. Further, basal phosphorylation of Akt (p-Akt (Ser-473)/total Akt) and GSK-3beta (GSK-3beta (Ser-9)/total GSK-3beta) are reduced 60-70% in primary myotubes from eNOS(-/-) mice. Treatment with the calcium ionophore, A23187 (0.4 microM, 1 h), increased phosphorylation of Akt and GSK-3beta by approximately 2-fold (P<0.05) in myotubes from WT mice, but had no effect on phosphorylation of these proteins in eNOS(-/-) myotubes. Additionally, A23187 treatment failed to induce nuclear translocation of the transcription factor, NFATc1, in eNOS(-/-) myotubes. Treatment with the nitric oxide donor, propylamine propylamine NONOate (PAPA-NO; 1 microM for 1 h) increased Akt and GSK-3beta phosphorylation, and induced NFATc1 nuclear translocation in WT and eNOS(-/-) myotubes, and eliminated differences from WT in the NOS knockout cultures. Parallel experiments in C2C12 myotubes found that Akt phosphorylation induced by NO or the guanylate cyclase activator, YC-1, is prevented by co-treatment with either a guanylate cyclase or PI3K inhibitor (10 microM ODQ or 25 microM LY2904002, respectively). These data suggest that eNOS activity is necessary for calcium-induced activation of the Akt pathway, and that nitric oxide is sufficient to elevate Akt activity in primary myotubes. NO appears to influence Akt signaling through a cGMP, PI3K-dependent pathway.
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PMID:Endothelial nitric oxide synthase is involved in calcium-induced Akt signaling in mouse skeletal muscle. 1968 97

Understanding the biological fate of graphene-based materials such as graphene oxide (GO) is crucial to assess adverse effects following intentional or inadvertent exposure. Here we provide first evidence of biodegradation of GO in the gastrointestinal tract using zebrafish as a model. Raman mapping was deployed to assess biodegradation. The degradation was blocked upon knockdown of nos2a encoding the inducible nitric oxide synthase (iNOS) or by pharmacological inhibition of NOS using l-NAME, demonstrating that the process was nitric oxide (NO)-dependent. NO-dependent degradation of GO was further confirmed in vitro by combining a superoxide-generating system, xanthine/xanthine oxidase (X/XO), with an NO donor (PAPA NONOate), or by simultaneously producing superoxide and NO by decomposition of SIN-1. Finally, by using the transgenic strain Tg(mpx:eGFP) to visualize the movement of neutrophils, we could show that inhibition of the degradation of GO resulted in increased neutrophil infiltration into the gastrointestinal tract, indicative of inflammation.
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PMID:Nitric oxide-dependent biodegradation of graphene oxide reduces inflammation in the gastrointestinal tract. 3278 15