Negative Modulation of Nitric Oxide Synthase by Nitric Oxide and Nitroso Compounds

Griscavage, Jeanette M.; Hobbs, Adrian J.; Ignarro, Louis J.

doi:10.1016/s1054-3589(08)61088-1

Cited by 137 publications

(81 citation statements)

References 49 publications

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“…The expression of iNOS was significantly increased after inhibition of nitric oxide production (Fig. 2), a finding consistent with the observation that nitric oxide regulates expression of iNOS in inflammatory cells (40,41). One of the remarkable findings in the present study, however, was that iNOS expression was significantly enhanced in cells transfected with catalase compared with vector-transfected controls, suggesting that intracellular H 2 O 2 production serves as an endogenous regulator of iNOS expression.…”

Section: Discussionsupporting

confidence: 92%

“…2). Inclusion of iNOS inhibitor (1400W) significantly increased iNOS protein levels (1.5-fold), consistent with previous reports of nitric oxide-induced downregulation of iNOS expression in inflammatory cells (40,41). Cells stably transfected with catalase demonstrated significant increased in cytokine-mediated expression of iNOS protein as compared with vector-transfected cells (1.5-fold increase; p Ͻ 0.05).…”

Section: Methodssupporting

confidence: 90%

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Expression of Inducible Nitric-oxide Synthase and Intracellular Protein Tyrosine Nitration in Vascular Smooth Muscle Cells

Fries

Paxinou

Themistocleous

et al. 2003

Journal of Biological Chemistry

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A significant increase in the induction of inducible nitric-oxide synthase (iNOS) protein expression and in the levels of nitrite plus nitrate was observed in rat aortic smooth muscle cells (RASMCs) stably transfected with catalase (RASMC-2C2) as compared with empty vector-transfected RASMC-V4 cells after exposure to cytokines and lipopolysaccharide. The increased expression of iNOS protein in the RASMC-2C2 cells was associated with a significant activation of nuclear transcription factor B, one of the transcriptional regulators of iNOS expression. The induction of iNOS was also accompanied by increased protein tyrosine nitration in both cell types as revealed by immunocytochemical staining and high pressure liquid chromatography with on-line electrospray ionization tandem mass spectrometry. Nitrotyrosine formation was inhibited by 1400W, an iNOS inhibitor, by 4-(2-aminoethyl) benzenesulfonyl fluoride, an inhibitor of NADPH oxidase, and by the superoxide dismutase mimetic M40403, but not by the peroxidase inhibitor 4-aminobenzoic hydrazide. Electron microscopy using affinity-purified anti-nitrotyrosine antibodies revealed labeling at the cytosolic side of the rough endoplasmic reticulum membranes, in the nucleus, occasionally in mitochondria, and consistently within the fibrillar layer underneath the plasma membrane. Collectively, the data in this model system indicate that hydrogen peroxide, by inhibiting the activation of nuclear transcription factor B, prevents iNOS expression, whereas superoxide contributes in a precise pattern of intracellular protein tyrosine nitration.

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Section: Discussionsupporting

confidence: 92%

Section: Methodssupporting

confidence: 90%

Expression of Inducible Nitric-oxide Synthase and Intracellular Protein Tyrosine Nitration in Vascular Smooth Muscle Cells

Fries

Paxinou

Themistocleous

et al. 2003

Journal of Biological Chemistry

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“…Pretreatment with S-NO-HSA, such as may be indicated in elective surgery, was even more beneficial. This could be because NO released by S-NO-HSA can counteract the consequences of the initial excessive NO production by eNOS 7 or because NO concentrations are maintained above baseline for an essentially longer period in the ischemic region. This further protects the enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that exogenous NO exhibits a negative feedback on the production of NO by eNOS (product inhibition of the enzyme). 7 The exogenous NO released by S-NO-HSA can therefore decrease production of NO by eNOS. For the smaller turnover rate of eNOS, the local arginine concentration around the enzyme may be sufficient to minimize or even prevent derangement.…”

mentioning

confidence: 99%

S -Nitroso Human Serum Albumin Treatment Reduces Ischemia/Reperfusion Injury in Skeletal Muscle via Nitric Oxide Release

et al. 2002

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Background-Peroxynitrite generated from nitric oxide (NO) and superoxide (O 2 Ϫ ) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O 2 Ϫ production generated also by endothelial NO synthase at diminished local L-arginine concentrations accompanying I/R. Methods and Results-During hindlimb I/R (2.5 hours/2 hours), in vivo NO was monitored continuously (porphyrinic sensor), and high-energy phosphates, reduced and oxidized glutathione (chromatography), and I/R injury were measured intermittently. Rabbits receiving human serum albumin (HSA) (controls) were compared with those receiving S-nitroso human serum albumin (S-NO-HSA) beginning 30 minutes before reperfusion for 1 hour or 30 minutes before ischemia for 3.5 hours (0.1 mol · kg Ϫ1 · h Ϫ1 ). The onset of ischemia led to a rapid increase of NO from its basal level (50Ϯ12 nmol/L) to 120Ϯ20 and 220Ϯ15 nmol/L in the control and S-NO-HSA-treated groups, respectively. In control animals, NO dropped below basal levels at the end of ischemia and to undetectable levels (Ͻ1 nmol/L) during reperfusion. In S-NO-HSA-treated animals, maximal NO levels never decreased below basal concentration and on reperfusion were 100Ϯ15 nmol/L (S-NO-HSA preischemia group, 175Ϯ15 nmol/L). NO supplementation by S-NO-HSA led to partial and in the preischemia group to total preservation of high-energy phosphates and glutathione status in reperfused muscle (eg, preischemia groups: ATP, 30.23Ϯ5.02 mol/g versus control, 15.75Ϯ4.33 mol/g, PϽ0.0005; % oxidized glutathione, 4.49Ϯ1.87% versus control, 22.84Ϯ6.39%, PϽ0.0001). S-NO-HSA treatment in all groups led to protection from vasoconstriction and reduced edema formation after reperfusion (eg, preischemia groups: interfiber area, 12.94Ϯ1.36% versus control, 27.83Ϯ1.95%, PϽ0.00001). Conclusions-Long

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“…On the other hand, NOS3 of vascular endothelial cells has been shown to be down-regulated 29,31 or up-regulated 30 by LPS. Furthermore, NO has been shown to inhibit NOS2 induction 32 or the catalytic activity of NOS2 33,34 in vitro. It is not clear how aortic nitric oxide synthases (NOSs) of portal vein-stenosed rats with baseline NO overproduction are regulated after LPS challenge.…”

mentioning

confidence: 99%

Abnormal regulation of aortic NOS2 and NOS3 activity and expression from portal vein-stenosed rats after lipopolysaccharide administration

et al. 1999

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Hyporeactivity to vasoconstrictors in aortae from portal vein-stenosed rats is associated with an increased activity of endothelial NO synthase (NOS3). In contrast, during sepsis, which is common in cirrhosis, vascular hyporeactivity is associated with an induction of inducible NOS2. The aim of this study was to investigate the in vitro reactivity to phenylephrine and the regulation of NOS2 and NOS3 in aortae from portal vein-stenosed rats after lipopolysaccharide (LPS) administration. Aortic vascular reactivity for phenylephrine, aortic NOS activity, and NOS2 and NOS3 protein expression were determined 5 hours after intravenous LPS or saline administration. Moreover, aortic NOS activity was measured after 5-hour in vitro incubation in LPS. LPS induced a significantly smaller decrease in aortic tension in portal vein-stenosed than in sham-operated rats. Under baseline conditions, aortic NOS activity and NOS3 protein expression were higher in portal vein-stenosed than in sham-operated rats, and NOS2 protein expression was not detected in aortae from either group. After LPS administration, NOS activity and NOS2 protein expression increased significantly less in portal vein-stenosed than in sham-operated rat aortae. Similar results were obtained after in vitro incubation with LPS. Endothelium removal or NOS3 inhibition with the calmodulin inhibitor, W7, increased NOS activity in the aortae of portal vein-stenosed rats after LPS incubation. In conclusion, in aortae of portal vein-stenosed rats exposed to LPS, no further decrease in aortic reactivity to phenylephrine was observed, and the induction of NOS2 was down-regulated. Endothelium removal or calmodulin inhibition inhibits NOS3 overactivity and leads to normalized NOS2 activation after LPS in aortae from portal vein-stenosed rats. (HEPATOLOGY 1999;30:698-704.)In cirrhosis, the occurrence of sepsis and the morbidity and mortality of septic shock are increased in humans and animal models. 1-4 Vasodilation in septic shock or during endotoxemia is caused part by an overproduction of nitric oxide (NO), which in this case is synthesized by the inducible NO synthase isoform (NOS2). [5][6][7][8][9][10] On the other hand, a hyperdynamic syndrome that results in systemic and splanchnic vasodilation, 11-13 a decreased responsiveness to vasoconstrictors, [14][15][16] and an increased cardiac output is also observed in portal hypertension with or without liver disease. In contrast to the hypothesis by Vallance and Moncada, 17 who suggested that circulating bacterial endotoxins induced vascular NOS2 in patients with cirrhosis, there is increasing evidence that the overproduction of NO in aortae of rats with extrahepatic portal hypertension 18-20 and cirrhotic rats without ascites [21][22][23] is caused by increased endothelial, constitutive NO synthase (NOS3) expression and activity without NOS2 induction. [23][24][25] In fact, because bacterial infections and sepsis are frequent in cirrhosis, NO overproduction in relation to both NOS3 overactivity and NOS2 induction may occ...

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Negative Modulation of Nitric Oxide Synthase by Nitric Oxide and Nitroso Compounds

Cited by 137 publications

References 49 publications

Expression of Inducible Nitric-oxide Synthase and Intracellular Protein Tyrosine Nitration in Vascular Smooth Muscle Cells

Expression of Inducible Nitric-oxide Synthase and Intracellular Protein Tyrosine Nitration in Vascular Smooth Muscle Cells

S -Nitroso Human Serum Albumin Treatment Reduces Ischemia/Reperfusion Injury in Skeletal Muscle via Nitric Oxide Release

Abnormal regulation of aortic NOS2 and NOS3 activity and expression from portal vein-stenosed rats after lipopolysaccharide administration

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