Nitric oxide synthase Pers

Abbreviations BSO, D.L-buthionine-. i -sulfoxime L , lipid alkyl radicals LH, lipid LO, Upid alkoxyl radicals LOO, Upid peroxyl radicals L-NAME, yV -nitro-L-arginine-methyl ester MBl, methylene bridge index (mean number of h -aUytic methylene positions per fatty add) NO, nitric oxide NOS, nitric oxide synthase NO, nitrite N02, nitrogen dioxide NO2CI, nitryl chloride O2 , superoxide OH, hydroxyl radical OL, epoxyaUyhc radical OLOO, epoxyperoxyl radical 0=NOO , peroxynitrite SNAP, S-nitroso-iV-acetyl-D.L-penicillamine SOD, superoxide dismutase contd. onp. 98, Subcellular Biochemistry, Volume 36 Phospholipid Metabolism in Apoptosis. 

Prosthetic groups contained within NOS. Nitric oxide synthases are isolated containing approximately one molecule each of heme, FAD, and FMN per subunit, and also contain variable quantities of tetrahydrobiopterin (0.1 to 1 molecule per subunit). 

The mechanistic basis of the neuroprotective activity of FAEE appears to rely not only on its general free-radical trapping or antioxidant activity per se, but also on its activity in mediating the induction of stress response proteins (HO-1 and F1SP72), cytoprotective (phase 2) proteins, and the parallel suppression of genes induced by pro-inflammatory cytokines, such as nitric oxide synthase (iNOS). 

Exhaled nitric oxide was used as the marker of airway inflammation after patients who had asthma were found to have increased levels of exhaled nitric oxide and nitric oxide synthase expression [17]. Exhaled nitric oxide correlated with a response to steroid, defined as change in pulmonary function testing, asthma symptoms, and BHR [18]. Patients who have symptoms of asthma who respond to steroids have higher exhaled nitric oxide than those who do not, implying inadequate anti-inflammatory treatment. The cutoff of exhaled nitric oxide for steroid response was determined to be approximately 48 parts per billion in one study [18], but no standards are widely used. 

Modification of human serum albumin by o-glucose impaired its antiapoptotic activity for endothelial cells a 50% loss of activity corresponded to about four fiuctosamine residues per protein molecule. In another study, D-fiuctose-albumin enhanced nitric oxide synthase activity and a consequent NO-dependent apoptosis in vascular endothelial cells. " This effect was also attributed to a possible mechanism of hyperglycemia-induced vasculopathy in diabetic patients. In proximal tubular epithelial cells, however, the effect of co-incubated D-fiuctose-albumin was the... 

Nitric oxide synthase dependent chemUumines-cence (counts per min with zymosan minus counts per min with zymosan -1- N -nitro-L-arginine meth-ylester) was determined as the amount of zymosan-stimulated chemiluminescence that was inhibitable by 1 mM N -nitro-L-arginine methylester added during the preincubation period (Jorens et al. 1993). 

There was no evidence from cell-free assay systems that carvedilol is a scavenger for 02 or NO (Asbrink et al. 2000). Carvedilol did not affect other reactions dependent on NO, e.g. spontaneous of formyl-methionyl-leucyl-phenylalanine-stimulated polymorphonuclear leucocyte migration or hpoxin A4-, fMLP-, or A23187-induced neutrophil cytotoxicity for human umbiUcal vein endothehal cells. Thus, these effects point to the possibility that carvedilol modulates the NADPH oxidase of polymorphonuclear leucocytes but leaves the nitric oxide synthase of phagocytes intact. Carvedilol exerted poor reactivity toward phenoxyl, alkoxyl, and per-oxyl radicals in acetonitrile solution nor did it show an appreciable antioxidant effect against either the peroxyl radical-induced oxidation of methyl Unole-... 

Inhibition of nitric oxide synthase by intraperi-toneal pre-medication of N -nitro-L-arginine for four days dramatically potentiated seizures induced in adult male Sprague-Dawley rats by 10 mg kainic acid per kg body weight (Maggio et al. 1995). 

Figure 3.2 Beneficial effects of folic acid on vascular wall. Folic acid circulates in human body as 5-methyltetrahydrofolate (5-MTHF). 5-MTHF lowers circulating homocysteine (Hey) levels, thus reducing systemic oxidative stress and Hcy-induced activation of prothrombotic mechanisms. In addition, vascular 5-MTHF has a favourable effect on intracellular Hey metabolism, attenuating Hcy-induced activation of NADPH oxidase isoforms (NOXs) in the vascular wall. Furthermore vascular 5-MTHF scavenges per se peroxynitrite (ONOO ) radicals in the vascular wall preventing the oxidation of vascular tetrahydrobiopterin (BH4) associated with endothelial nitric oxide synthase (eNOS) uncoupling and diminished vascular nitric oxide (NO) bioavailability. In total through these effects 5-MTHF lowers vascular oxidative and nitrosative stress. Thus by modulating vascular redox, 5-MTHF inhibits activation of proinffammatory pathways which orchestrate vascular wall inflammation and perpetuate endothelial dysfunction and atherogenesis development (unpublished).

Recent discovery of nitric oxide ( NO), which controls and influences a number of critical physiological processes, as a mammalian metabolic intermediate has stimulated rapid progress of studies on nitric oxide synthase (NOS) [267-269]. The formation of NO from L-arginine in mammalian cells is catalyzed by NOS. The inducible NOS has now been known to contain a cytochrome P-450 type iron-protoporphyrin IX prosthetic group and 1 equiv each of FAD and FMN per subunit [270, 271]. Further, NOS requires NADPH to proceed the reactions. Interestingly, P-450 itself has been demonstrated to catalyze NO synthesis [272, 273]. While the detail of the reaction mechanism is still obscure. Scheme 17 summarizes proposed reaction sequences [269]. 

Stuehr and Ikeda-Saitos used EPR and optical spectroscopy to characterize nitric oxide synthases isolated from brain and ey tokine-aetivated maerophages. They found that both enzymes contain two molecules of iron-protoporphyrin IX per protein homodimer and showed that the optieal and EPR speetroscopie... 

Once perfusion is recovered, vascular regulatory processes are not fully functional, such as endothelial nitric-oxide synthase (eNOS), which becomes uncoupled and instead of generating NO produces superoxide, contributing to oxidative stress and triggering an inflammatory cascade. The additive role of oxidative and nitrosative stress results in increased NO release from inducible NOS (iNOS) in perivascular tissue and from macrophages/monocytes. The NO generated by iNOS is metabolized to per-oxynitrite, which is cytotoxic to tissues. 

FIGURE 2 Nitric oxide (NO) synthase inhibition with nitro-L-arginine (L-NA) increases basal total pulmonary resistance per kilogram (TPR/KG) and attenuates the decline in TPR during ventilation with and without hyperoxia in the premature lamb. As shown, the immature lung is responsive to inhaled NO (20 ppm). IMV, intermittent mandatory ventilation BL, baseline. [From Kinsella et al. (35).]... 

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