NO Metabolism (no + metabolism)

Distribution by Scientific Domains

Selected Abstracts

Gestational diabetes affects platelet behaviour through modified oxidative radical metabolism

L. Mazzanti
Abstract Aims Patients with Type 1 and Type 2 diabetes mellitus show altered platelet function including decreased nitric oxide synthase (NOS) activity and increased peroxynitrite production. Gestational diabetes mellitus (GDM) is a clinical condition which is ideal for evaluating short-term effects of impaired glucose metabolism, ruling out the possibility that the platelet abnormalities are a consequence of diabetic complications. The aim of the present work was to study NO metabolism in platelets from pregnant women with GDM. The production of peroxides was also studied as it is strongly involved in peroxynitrite formation. Methods Platelet NOS activity and peroxynitrite production, levels of hydroperoxides and thiobarbituric acid reactive substances (TBARS) in platelet membranes in the basal state and after in vitro peroxidative stress with phenylhydrazine were determined in 40 pregnant women with GDM, 40 healthy pregnant women (pregnant controls) of comparable age and gestational age, and 15 healthy non-pregnant women (controls). Results NOS activity was significantly increased in both groups of pregnant women compared with non-pregnant ones, and in GDM women compared with pregnant controls. Production of peroxynitrite was higher in GDM women than in pregnant controls, who also had significantly reduced production compared with non-pregnant women. Basal levels of peroxidation of the platelet membranes evaluated either by hydroperoxide content and TBARS levels or the susceptibility to peroxidation were increased in GDM patients in comparison with both control groups. Conclusions We have shown a modification in platelet NO and peroxynitrite production and an increase in platelet indicators of oxidative stress in GDM women compared with healthy pregnant women which might be at the basis of a cellular dysfunction. [source]

Mutual changes of thioredoxin and nitrosothiols during biliary cirrhosis: Results from humans and cholestatic rats,

HEPATOLOGY, Issue 2 2007
Ignazio Grattagliano
Cholestasis is associated with changes in NO metabolism and thiol oxidation. Thioredoxin contributes to regulate vascular tone and intracellular redox status by cleaving nitrosothiols and maintaining ,SH groups. This study investigated the changes in circulating thioredoxin and nitrosothiols and the relationship with protein sulfhydryls (PSH), hepatic concentrations, hyaluronate, and histology in patients with primary biliary cirrhosis (PBC) and in rats with bile duct ligation (BDL). PSH in erythrocytes were significantly decreased in stage III and IV PBC and at day 10 after BDL. Compared with controls, erythrocyte thioredoxin levels were higher in stage I through III PBC and lower in stage IV patients. Serum thioredoxin levels were significantly higher in PBC stages I and II and lower in stages III and IV. Serum nitrosothiols were higher in all PBC patients and inversely related to thioredoxin and hyaluronate. In rats, serum, hepatic, and mitochondrial thioredoxin had initially increased after BDL (day 1-3) and then decreased. After day 7 BDL, nitrosothiols were 10-fold increased in serum and liver, and even higher in mitochondria. In the liver, thioredoxin was inversely related to both nitrosothiols and PSH. In rats, the difference in time average changes from baseline among serum, hepatic, and erythrocyte thioredoxin suggests that most of circulating thioredoxin originates from the liver. Conclusion: Our findings indicate that cholestasis is associated with significant mutual and interrelated changes between circulating and hepatic thioredoxin and nitrosothiols. The increase of hepatic, mitochondrial, and circulating nitrosothiols with ongoing cholestasis suggests an active participation of NO in both liver injury and extrahepatic changes. (HEPATOLOGY 2007;45:331,339.) [source]

Cerebral blood flow and oxygen metabolism measured with the Kety,Schmidt method using nitrous oxide

Background: The Kety,Schmidt method is the reference method for measuring global cerebral blood flow (CBF), cerebral metabolic rates (CMR) and flux, especially where scanners are unavailable or impractical. Our primary objective was to assess the repeatability of the Kety,Schmidt method in a variety of different approaches using inhaled nitrous oxide (N2O) as the tracer, combined with photoacoustic spectrometry. A secondary objective was to assess the impact of this tracer on the systemic vascular concentration of nitrite (NO2,). Methods: Twenty-nine healthy male volunteers underwent 61 CBF measurements by breathing a normoxic gas mixture containing 5% N2O until tension equilibrium. Paired blood samples were collected from an arterial and a jugular bulb catheter in the saturation or desaturation phase, by continuous or the discontinuous sampling. N2O concentration was measured with photoacoustic spectrometry after equilibration of blood samples with air. CBF was calculated by the Kety,Schmidt equation. CMR of oxygen (CMRO2) was determined by the Fick principle. NO2, in plasma and red blood cells (RBC) was measured by ozone-based chemiluminescence. Results: The most robust approach for CBF measurement was achieved by discontinuous sampling in the desaturation phase [CBF, 64 (95% confidence interval, 59,71 ml)] 100 g/min; CMRO2 1.8 (1.7,2.0) ,mol/g/min). The tracer did not influence plasma or RBC NO2, (P>0.05 vs. baseline). Conclusion: These findings confirm the reliability and robustness of the Kety,Schmidt method using inhaled N2O for the measurement of global CBF and CMR. At the low tracer concentration used, altered NO metabolism is unlikely to have affected cerebral haemodynamic function. [source]

Functional analysis of NsrR, a nitric oxide-sensing Rrf2 repressor in Neisseria gonorrhoeae

Vincent M. Isabella
Summary Nitric oxide (NO) has been shown to be an important component of the human immune response, and as such, it is important to understand how pathogenic organisms respond to its presence. In Neisseria gonorrhoeae, recent work has revealed that NsrR, an Rrf2-type transcriptional repressor, can sense NO and control the expression of genes responsible for NO metabolism. A highly pure extract of epitope-tagged NsrR was isolated and mass spectroscopic analysis suggested that the protein contained a [2Fe,2S] cluster. NsrR/DNA interactions were thoroughly analysed in vitro. Using EMSA analysis, NsrR::FLAG was shown to interact with predicted operators in the norB, aniA and nsrR upstream regions with a Kd of 7, 19 and 35 nM respectively. DNase I footprint analysis was performed on the upstream regions of norB and nsrR, where NsrR was shown to protect the predicted 29 bp binding sites. The presence of exogenously added NO inhibited DNA binding by NsrR. Alanine substitution of C90, C97 or C103 in NsrR abrogated repression of norB::lacZ and inhibited DNA binding, consistent with their presumed role in co-ordination of a NO-sensitive Fe,S centre required for DNA binding. [source]