Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.5.1.19 (NOS)
7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is normally synthesized inside skeletal muscle fibers by both endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases. In this study, we evaluated the influence of hypobaric hypoxia on the expression of NOS isoforms, argininosuccinate synthetase (AS), argininosuccinate lyase (AL), and manganese superoxide dismutase (Mn SOD) in the ventilatory muscles. Rats were exposed to hypobaric hypoxia ( approximately 95 mmHg) from birth for 60 days or 9-11 mo. Age-matched control groups of rats also were examined. Sixty days of hypoxia elicited approximately two- and ninefold increases in diaphragmatic eNOS and nNOS protein expression (evaluated by immunoblotting), respectively, and about a 50% rise in diaphragmatic NOS activity. In contrast, NOS activity and the expression of these proteins declined significantly in response to 9 mo of hypoxia. Hypoxia elicited no significant alterations in AS, AL and Mn SOD protein expression. Moreover, the inducible NOS (iNOS) was not detected in normoxic and hypoxic diaphragmatic samples. We conclude that diaphragmatic NOS expression and activity undergo significant adaptations to hypobaric hypoxia and that iNOS does not participate in this response.
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PMID:Regulation of diaphragmatic nitric oxide synthase expression during hypobaric hypoxia. 1095 27

Organic nitrites are nitric oxide (NO) donors that are used predominantly as inhalant drugs of abuse and have been shown to have immunomodulating effects. NO donors can modulate NOS activity and expression, thus altering the level of endogenous NO production. NO can react with superoxide (O(*)(2)(-)) to form peroxynitrite (ONOO(-)), which can nitrate tyrosine residues in proteins and alter tyrosine phosphorylation. We investigated the effects of inhaled isobutyl nitrite (ISBN) on NOS expression, tyrosine nitration, and tyrosine phosphorylation in selected organs of rats. Following exposures of 109 and 1517 ppm ISBN for 4 h, the lung, spleen, liver, and kidney were removed and assayed by SDS-PAGE for NOS III (eNOS), NOS II (iNOS), nitrotyrosine (NT)- and phosphotyrosine (PT)-immunoreactive proteins using specific antibodies. ISBN at 1517 ppm, but not 109 ppm, caused an increase in NOS III expression in the liver and kidney, but not in the lung and spleen. No apparent effect on NOS II expression was observed in these organs. The expressions of NT and PT protein bands (30-200 kDa) were increased in the liver and kidney, but not in the lung and spleen. This increase in NT persisted for 24 h post-exposure. Increased NOS III expression in the liver and kidney may promote peroxynitrite formation and contribute to the increase in NT and PT immunoreactivity. ISBN inhalation may thus cause changes in cellular signaling involving tyrosine phosphorylation. These findings may suggest a mechanistic basis for the apparent immunotoxicity associated with nitrite abuse.
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PMID:Nitrite inhalation in rats elevates tissue NOS III expression and alters tyrosine nitration and phosphorylation. 1096 67

1. Experiments were designed to investigate the effects of the inducible nitric oxide synthase (iNOS) stimulator, lipopolysaccharide (LPS), on noradrenaline (NA) responses and on NOS activity and its expression in intact mesenteric resistance arteries (MRAs) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. In MRAs from WKY, LPS (10 microg ml(-1); 1-5 h) reduced the vasoconstrictor responses to NA (0.1 - 30 microM) in the presence, but not in the absence of L-arginine (L-Arg, 10 microM). However, in SHR arteries, LPS induced an incubation-time dependent reduction of NA responses in the absence, as well as the presence, of L-Arg. The LPS inhibitory effect was reduced by the non-specific NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME, 100 microM) and the selective iNOS inhibitor, aminoguanidine (100 microM). 3. L-NAME alone similarly shifted the concentration-response curve to NA leftward in arteries from both strains, while aminoguanidine had no effect. L-Arg shifted the curve to NA rightward only in SHR MRAs. 4. Basal activity of both iNOS and constitutive NOS (conversion of [(3)H]-L-Arg to [(3)H]-L-citrulline) was similar in arteries from both strains. After 5 h incubation with LPS, only iNOS activity in arteries from SHR was increased. 5. Basal iNOS protein expression was undetectable; basal endothelial (eNOS) protein expression was similar in arteries from both strains, while neuronal (nNOS) was greater in arteries from SHR. LPS induced iNOS protein expression, that was higher in arteries from SHR than in those from WKY. 6. These results indicate that NO production, via iNOS induction, is greater than in those from MRAs from SHR to WKY.
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PMID:Influence of hypertension on nitric oxide synthase expression and vascular effects of lipopolysaccharide in rat mesenteric arteries. 1099 10

Previous studies have demonstrated that responses to endothelium-dependent vasodilators are absent in the aortas from mice deficient in expression of endothelial nitric oxide synthase (eNOS -/- mice), whereas responses in the cerebral microcirculation are preserved. We tested the hypothesis that in the absence of eNOS, other vasodilator pathways compensate to preserve endothelium-dependent relaxation in the coronary circulation. Diameters of isolated, pressurized coronary arteries from eNOS -/-, eNOS heterozygous (+/-), and wild-type mice (eNOS +/+ and C57BL/6J) were measured by video microscopy. ACh (an endothelium-dependent agonist) produced vasodilation in wild-type mice. This response was normal in eNOS +/- mice and was largely preserved in eNOS -/- mice. Responses to nitroprusside were also similar in arteries from eNOS +/+, eNOS +/-, and eNOS -/- mice. Dilation to ACh was inhibited by N(G)-nitro-L-arginine, an inhibitor of NOS in control and eNOS -/- mice. In contrast, trifluoromethylphenylimidazole, an inhibitor of neuronal NOS (nNOS), decreased ACh-induced dilation in arteries from eNOS-deficient mice but had no effect on responses in wild-type mice. Indomethacin, an inhibitor of cyclooxygenase, decreased vasodilation to ACh in eNOS-deficient, but not wild-type, mice. Thus, in the absence of eNOS, dilation of coronary arteries to ACh is preserved by other vasodilator mechanisms.
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PMID:Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase-deficient mice. 1100 79

Nitric oxide (NO) is produced by NO synthases (nNOS, iNOS, and eNOS) expressed in various human tissues and depending on the amount of NO produced in each tissue, the physiological function of NO is determined. However, due to the difficulty in obtaining normal human tissues, little is known about the basal levels of each of the three NOS mRNAsand proteins expressed constitutively in various human tissues. Results of the present study indicate that the basal levels of each of the three NOS mRNAs and proteins expressed in various regions of brain and peripheral tissues are different both in their sizes and in their contents. In Northern blot analysis, two different-sized mRNAs were found for each NOS isozymes: for the nNOS, approximately 12 and <12 kb mRNAs; for the iNOS, 4.2 and 4.5 kb mRNAs; for the eNOS, 4.2 and 4.4 kb mRNAs. In the Western blot, several different-sized NOS proteins were detected ( approximately 160, approximately 140, and approximately 130 kDa for nNOS; approximately 130 kDa for iNOS and eNOS) with tissue-specific expression patterns. These differential expression patterns of NOS mRNAs and proteins were caused by alternative splicing in the open-reading frame, and 5'- and/or 3'-untranslated regions of NOS mRNAs. These results suggest that regulation for differential expression of the three NOS genes in various human tissues may occur by alternative splicing of the NOS mRNAs in tissue-specific patterns.
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PMID:Differential and constitutive expression of neuronal, inducible, and endothelial nitric oxide synthase mRNAs and proteins in pathologically normal human tissues. 1102 Mar 35

The objective of this study was to determine what roles the endothelial cell and inducible isoforms of nitric oxide synthase (eNOS, iNOS) play in ischemia and reperfusion (I/R)-induced liver injury in vivo in mice genetically deficient in each isoform of NOS. We found that 45 min of partial (70%) liver ischemia and 5 h of reperfusion induced substantial liver injury as assessed by the release of large and significant amounts of the liver-specific enzyme alanine aminotransferase (ALT) into the serum of wild-type (wt) mice. The enhanced ALT levels were not due to increased recruitment of potentially damaging PMNs, which could mediate hepatocyte injury, as neither histopathological inspection nor quantitative MPO determinations revealed the presence of PMNs in the liver at this time point. In addition, we observed a significant enhancement in liver injury in eNOS-deficient but not iNOS-deficient mice subjected to liver I/R compared to postischemic wt mice. Taken together, these data suggest that eNOS- but not iNOS-derived NO plays an important role in limiting or downregulating I/R-induced liver injury in vivo following 5 h of reperfusion.
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PMID:Nitric oxide synthase and postischemic liver injury. 1102 58

C(60)-Fullerene monomalonate adducts inactivate selectively the neuronal nitric oxide synthase isoform in a manner completely preventable by the concurrent presence of superoxide dismutase and catalase. This inactivation is time-, fullerene concentration-, and turnover-dependent and is not reversible by dilution. The di(carboxypropan-3-ol)methano-[60]-fullerene (diol adduct) has no effect on NADPH consumption by nNOS as measured in the absence of arginine substrate, but dramatically increases NADPH consumption in the presence of arginine. This fullerene-enhanced NADPH consumption is linked to oxygen as electron acceptor and is accompanied by the increased production of hydrogen peroxide. These effects of fullerene monomalonate adducts are unique to the nNOS isoform and are not observed using either the iNOS or the eNOS isoform. The inhibitory effects of fullerene monomalonate adducts are unaltered and insurmountable by increased concentrations of arginine, tetrahydrobiopterin, or calmodulin. These observations indicate that fullerene monomalonate adducts uncouple in the presence of arginine the formation of reactive oxygen intermediates from NO production by nNOS. These reactive oxygen intermediates dissociate from the enzyme and, acting from solution, inactivate NOS NO forming activity.
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PMID:C60-Fullerene monomalonate adducts selectively inactivate neuronal nitric oxide synthase by uncoupling the formation of reactive oxygen intermediates from nitric oxide production. 1114 Oct 54

This study examined the notion that exogenous generation of nitric oxide (NO) modulates NOS gene expression and activity. Bovine pulmonary artery endothelial cells (BPAEC) were treated with the NO donors, 1 mM SNAP (S-nitroso-N-acetylpenicillamine), 0.5 mM SNP (sodium nitroprusside) or 0.2 microM NONOate (spermine NONOate) in medium 199 containing 2% FBS. Controls included untreated cells and cells exposed to 1 mM NAP (N-acetyl-D-penicillamine). NOS activity was assessed using a fibroblast-reporter cell assay; intracellular Ca2+ concentrations were assessed by Fura-2 microfluorometry; and NO release was measured by chemiluminescence. Constitutive endothelial (e) and inducible (i) NOS gene and protein expression were examined by northern and western blot analysis, respectively. Two hours exposure to either SNAP or NONOate caused a significant elevation in NO release from the endothelial cells (SNAP = 51.4 +/- 5.9; NONOate = 23.8 +/- 4.2; control = 14.5 +/- 2.8 microM); but A23187 (3 microM)-stimulated NO release was attenuated when compared to controls. Treatment with either SNAP or NONOate for 2 h also resulted in a significant increase in NOS activity in endothelial homogenates (SNAP = 23.6 +/- 2.5; NONOate= 29.8 +/- 7.7; control = 14.5 +/- 2.5fmol cGMP/microg per 10(6) cells). Exposure to SNAP and SNP, but not NONOate, for 1 h caused an increase in intracellular calcium. Between 4 and 8 h, SNAP and NONOate caused a 2- to 3-fold increase in eNOS, but not iNOS, gene (P < 0.05) and protein expression. NAP had little effect on either eNOS gene expression, activity or NO production. Our data indicate that exogenous generation of NO leads to a biphasic response in BPAEC, an early increase in intracellular Ca2+, and increases in NOS activity and NO release followed by increased expression of the eNOS gene, but not the iNOS gene. We conclude that eNOS gene expression and activity are regulated by a positive-feedback regulatory action of exogenous NO.
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PMID:Nitric oxide donors regulate nitric oxide synthase in bovine pulmonary artery endothelium. 1114 6

Past studies have demonstrated that 17beta-estradiol (E(2)beta) increases endothelial nitric oxide (NO) synthase (eNOS) activity in uterine, heart, and skeletal muscle and in cultured human endothelial cells. However, little is known about E(2)beta regulation of NO synthesis in the pulmonary vasculature. The present study evaluated E(2)beta regulation of eNOS function in pulmonary arteries and thoracic aortas. We hypothesized that E(2)beta upregulates vascular NO release by increasing eNOS expression. To test this, NO-dependent vasodilation was assessed in isolated perfused lungs and aortic rings from ovariectomized Sprague-Dawley rats treated for 1 wk with 20 microg/24 h of E(2)beta or vehicle. Expression of eNOS was evaluated by Western blot and immunohistochemistry. Also, a RNase protection assay determined eNOS mRNA levels in lung and aortic homogenates from control and treated rats. Vasodilation to ionomycin in lungs from the E(2)beta-treated group was enhanced compared with that in control animals. Endothelium-intact aortic rings from E(2)beta-treated animals also demonstrated augmented endothelium-dependent dilation. Both responses were blocked with NOS inhibition. Immunostaining for eNOS was greater in pulmonary arteries and aortas from E(2)beta-treated compared with control rats. However, mRNA levels did not differ between groups. Thus we conclude that in vivo E(2)beta treatment augments endothelium-dependent dilation in aorta and lung, increasing expression of eNOS independently of sustained augmented gene transcription.
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PMID:17beta-estradiol increases nitric oxide-dependent dilation in rat pulmonary arteries and thoracic aorta. 1115 40

We determined the existence and role of beta(2)-adrenergic receptor in cultured BAECs through the effect of a beta-blocker having NO releasing action; 3,4-dihydro-8(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran; nipradilol on eNOS and eNOS regulatory protein caveolin-1. beta(2) receptor exists in BAECs. eNOS mRNA and protein were up-regulated by its treatment whereas those of caveolin were not altered considerably. This eNOS up-regulatory action was abolished by beta(2) receptor antagonist, ICI-118551. Increase of NO metabolites, protein and mRNA of eNOS was also partially inhibited by co-treatment of NOS inhibitor, L-NA with nipradilol. This is the first investigation of the action of non-selective beta blocker on eNOS through beta(2) receptor. The drug increases NO on incubation with BAECs about 50% as a NO donor and about 50% as results of eNOS up-regulation.
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PMID:Up-regulation of endothelial nitric oxide synthase through beta(2)-adrenergic receptor--the role of a beta-blocker with NO-releasing action. 1116 60


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