Formation of Nitric Oxide

The early stages of bone pathology in rheumatoid disease manifest as periarticular osteoporosis and juxta-articular bone erosion. Osteoclast overactivity is the predominant influence in such bone erosion and NO has a direct inhibitory efiect on osteoclastic bone resorption (MacIntyre et al., 1991). Endothelial cells, present in abundance and in close proximity to the osteoclast may therefore play a role in down-regulating osteoclast activity through the production of NO. Since the osteoclast is of macrophage lineage, it is likely to be 

Chin et al. (1992) have su ested that oxidized LDL and high-density lipoprotein (HDL) inactivate endothelial cell-derived NO. NO inactivation was due to the oxidized lipids within the lipoprotein particles and was thought to be explained by a chemical reaction between the lipoproteins and NO. Other investigators have shown that relaxation of vascular smooth muscle by acetylcholine or bradykinin (endothelium-dependent vasodilators) is inhibited by LDL (Andrews etal., 1987). The role of NO in the modification of LDL is discussed in full detail in Chapter 2. 

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The advantages of thermal incineration are that it is simple in concept, has a wide application, and results in almost complete destruction of pollutants with no liquid or solid residue. Thermal incineration provides an opportunity for heat recovery and has low maintenance requirements and low capital cost. Thermal incineration units for small or moderate exhaust streams are generally compact and light. Such units can be installed on a roof when the plant area is limited. = The main disadvantage is the auxiliary fuel cost, which is partly offset with an efficient heat-recovery system. The formation of nitric oxides during the combustion processes must be reduced by control of excess air temperature, fuel supply, and combustion air distribution at the burner inlet, The formation of thermal NO increases dramatically above 980 Table 13.10)... 

NO synthases (NOS, L-arginine, NADPH oxygen oxi-doreductases, nitric oxide forming EC 1.14.13.39) represent a family of enzymes that catalyze the formation of nitric oxide (NO) from the amino acid L-arginine. In mammals, three isoforms of NOS have been identified. They are termed neuronal NOS (nNOS, NOS I, NOS1), inducible NOS (iNOS, NOS H, NOS2), and endothelial... 

Thus far we have studied thermodynamics and kinetics imder the assumption that the systems of interest are in equilibrium. However, some natural systems have reaction rates so slow that they exist for long periods under non-equilibrium conditions. The formation of nitric oxide serves as an interesting example. 

In conclusion, it should be stressed that the competition between pro- and antiapoptotic effects of nitric oxide must probably depends on its relevant levels [137] the low physiological levels of NO principally suppress the apoptotic pathway by several mechanisms, whereas the higher rates of NO production may overcome cellar protective mechanisms and stimulate apoptosis. Furthermore, the simultaneous formation of nitric oxide and superoxide increases the possibility of apoptosis activation due to the formation of peroxynitrite. 

The formation of nitric oxide in microsomes results in the inhibition of microsomal reductase activity. It has been found that the inhibitory effect of nitric oxide mainly depend on the interaction with cytochrome P-450. NO reversibly reacts with P-450 isoforms to form the P-450-NO complex, but at the same time it irreversibly inactivates the cytochrome P-450 via the modification of its thiol residues [64]. Incubation of microsomes with nitric oxide causes the inhibition of 20-HETE formation from arachidonic acid [65], the generation of reactive oxygen species [66], and the release of catalytically active iron from ferritin [67],... 

Andronik-Lion, V., Boucher, J. L., Delaforge, M., Henry, Y., Mansuy, D., Formation of nitric oxide by cytochrome P450-catalyzed oxidation of aromatic amidoximes, Biochem. 

Mansuy, D., Boucher, J. L., Oxidation of N-hydroxyguanidines by cytochromes P450 and NO-synthases and formation of nitric oxide, Drug Metah. Rev. 34 (2002), p. 593-606... 

J. L. Zweier, P. Wang, A. Samouilov, P. Kuppusamy, Enzyme-Independent Formation of Nitric Oxide in Biological Tissues , Nature Med. 1995, 1, 804 - 809. 

Use such reasonable approximations as (1) Air consists solely of nitrogen and oxygen in exactly 4 1 volume ratio (2) other chemical surface reactions can be neglected because of the short times (4) ideal shock wave relations for pure air with constant specific heats may be used despite the formation of nitric oxide and the occurrence of high temperature. 

The NO2 can also be produced by reactions between sulfur and potassium nitrate (KNO3) with the formation of nitric oxide (NO) and nitrogen dioxide (NO2) as shown in reactions (2.3) and (2.4) ... 

Next consider the formation of nitric oxide from air... 

Oxides of nitrogen also contribute to the formation of acid deposition. These oxides are formed whenever sufficient heat is generated in a power generating plant or industrial operation to allow the formation of nitric oxide from nitrogen and oxygen ... 

C. Nitric oxide is an important compound that acts as a biological messenger in many physiological responses. L-Citrulline is a product of the oxidation of L-argenine in the formation of nitric oxide. Bradykinin is formed from a precursor kininogen. 

This reduces the rotational broadening and makes the vibrational subspectra apparent as a series of multiple peaks. If hydroxyl radical scavengers such as buffer components, the glass or plastic wall of test tubes, or trace metal contaminants are present, exposure to light will result in the formation of nitric oxide from... 

Knowles, R. G., Palacios, M., Palmer, R. M. J., and Moncada, S. (1989). Formation of nitric oxide from L-arginine in the central nervous system A transducer mechanism for stimulation of the soluble guanylate cyclase. Proc. Natl. Acad. Sci. U.S.A. 86, 5159-5162. 

Palmer, R. M. J., Rees, D. D., Ashton, D. S., and Moncada, S. (1988b). L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem. Biophys. Res. Commun. 153, 1251-1256. 

If jS-cell production of nitric oxide participates in IDDM, human islets must produce nitric oxide in response to cytokines. We have shown that a combination of cytokines (lL-1, IFN, and TNF) induce the formation of nitric oxide by isolated human islets (Corbett et al., 1993b). The formation of nitric oxide has been demonstrated by cytokine-induced cGMP accumulation, nitrite formation, and EPR-detectable iron-nitrosyl complex formation (Fig. 12), all of which were prevented by NMMA. The cytokine combination of IFN and lL-1 are required for nitrite production, while TTSIF potentiates IL-1 and IFN-induced nitrite formation by human islets. The cytokine combination of lL-1, TNF, and IFN also influences the physiological function of insulin secretion by human islets. Low concentrations of this cytokine combination slightly stimulate insulin secretion, while high concentrations inhibit insulin secretion, similar to the concentration-dependent effects of lL-1 on rat islet function. NMMA partially prevents the inhibitory effects of this cytokine combination on insulin secretion from human islets, suggesting that nitric oxide may participate in )3-cell dysfunction associated with IDDM. 

We believe that the /3 cell is a source of nitric oxide production by human islets because (1) IL-1 and IFN-induced nitric oxide production by human macrophages has not been clearly demonstrated (2) the cytokine combination of IL-1, IFN, and TNF induces the formation of nitric oxide by human islets either freshly isolated or cultured for 7 days at 25°C (a procedure which removes 80-90% of nonendocrine cells from the islet) and also by islets cryoperserved and (3) NADPH—diaphorase staining reveals that approximately 60-70% of human islet cells treated with cytokines stain for NADPH-diaphorase (J. A. Corbett and M. L. McDaniel, unpublished data). TTiis staining procedure has been shown to colocalize with nitric oxide synthase in a number of cells including rat islets (Corbett et al., 1993c), and nitric oxide synthase has been demonstrated to contain NADPH-diaphorase enzymatic activity (Dawson et al., 1991 Hope et... 

Effects of cytokines on the formation of nitric oxide by human islets as determined by EPR spectroscopy. Human islets were treated for 18 hr with 75 U/ml lL-1, 3.5 nM TNF-a, and 750 U/ml IFN-y, the islets were then isolated, and EPR spectroscopy was performed as described previously (Corbett et al., 1993b). Cytokine induced nitric oxide formation is demonstrated by the genetation of an EPR detectable g = 2.04 iton-nitrosyl complex which is prevented by 0.5 mM NMMA. Reproduced with permission from Proc. Nall. Acad. Set. U S.A. (Corbett et al., 1993b). 

Corbett, J. A., Sweetland, M. A., Lancaster, J. R., Jr., and McDaniel, M. L. (1993a). A 1 hour pulse with IL-lb induces the formation of nitric oxide and inhibits insulin secretion by rat islets of Langerhans Evidence for a tyrosine kinase signaling mechanism. FASEBJ. 7, 369-374. 

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