Endothelial NO synthase

Endothelial NO Synthase (eNOS) expression is relatively specific for endothelial cells. However, the isozyme has also been detected in certain neurons of the brain, in syncytiotrophoblasts of human placenta and in LLC-PKi kidney tubular epithelial cells. 

Forstermann U (2006) Janus-faced role of endothelial NO synthase in vascular disease - Uncoupling of NADPH oxidation from NO synthesis and its pharmacological reversal. Biol Chem 387 1521-1533... 

Forstermann U, Miinzel T (2006) Endothelial NO synthase in vascular disease — from marvel to menace. Circulation 113 1708-1714... 

The inactivation of enzymes containing the zinc-thiolate moieties by peroxynitrite may initiate an important pathophysiological process. In 1995, Crow et al. [129] showed that peroxynitrite disrupts the zinc-thiolate center of yeast alcohol dehydrogenase with the rate constant of 3.9 + 1.3 x 1051 mol-1 s-1, yielding the zinc release and enzyme inactivation. Later on, it has been shown [130] that only one zinc atom from the two present in the alcohol dehydrogenase monomer is released in the reaction with peroxynitrite. Recently, Zou et al. [131] reported the same reaction of peroxynitrite with endothelial NO synthase, which is accompanied by the zinc release from the zinc-thiolate cluster and probably the formation of disulfide bonds between enzyme monomers. The destruction of zinc-thiolate cluster resulted in a decrease in NO synthesis and an increase in superoxide production. It has been proposed that such a process might be the mechanism of vascular disease development, which is enhanced by diabetes mellitus. 

NADH-ubiquinone reductase) and the second one was complex II (succinate-ubiquinone reductase). Chiesi and Schwaller [101] found that quercetin and tannin inhibited neuronal constitutive endothelial NO synthase. 

Fig. 12.2 Immunogold localization of endothelial NO synthase (NOS3) in skeletal muscles, a Immunogold labeling of NOS3 in subsarcolemmal mitochondria, b Inside of the sarcoplasm NOS3 is localized along the contractile fibers, in the sarcoplasmic reticulum and in mitochondria. EPON embedding, etching with sodium ethoxide, antigen retrieval in citrate buffer, pH 6.0. 12 nm immunogold.

Nitric Oxide Synthase Expression and Activity Nitric Oxide Synthase Uncoupling. Inhibitory effects of quercetin on the activity or expression of endothelial NO synthases (eNOS and iNOS) has been reported but only at high concentrations (< 50 pM) [Camuesco et al., 2004 Chiesi and Schwaller 1995]. Therefore, direct changes in endothelial NO expression or activity, even when relevant to other polyphenolics, do not appear to be physiologically relevant for quercetin. However, quercetin may restore NOS expression or activity when unpaired by pathological stimuli. In fact, eNOS expression, which is up-regulated in SHR, can be corrected by chronic quercetin administration... 

Chiesi M, Schwaller R. 1995. Inhibition of constitutive endothelial NO-synthase activity by tannin and quercetin. Biochem Pharmacol 49 495-501. 

Wallerath T, Li H, Godtel-Ambrust U, Schwarz PM, Forstermann U. 2005. A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide 12 97-104. 

Millanvoye-Van Brussel E., Topal G., Brunet A., Do Phaw T., Deckert V., Rendu F., and David-Dufilho M. (2004). Lysophosphatidylcholine and 7-oxocholesterol modulate Ca2+ signals and inhibit the phosphorylation of endothelial NO synthase and cytosolic phospholipase A2. Biochem. J. 380 533-539. 

Mancusi, G., C. Hutter, S. Baumgartner-Parzer, K. Schmidt, W. Schutz, and V. Sexl. 1996. High-glucose incubation of human umbilical-vein endothelial cells does not alter expression and function either of G-protein alpha-subunits or of endothelial NO synthase. Biochem. J. 315(Pt l) 281-287. 

Ndiaye, M., Chataigneau, M., Lobysheva, 1., Chataigneau, T., Schini-Kerth, V. B. (2005). Red wine polyphenol-induced, endothelium-dependent NO-mediated relaxation is due to the redox-sensitive P13-kinase/Akt-dependent phosphorylation of endothelial NO-synthase in the isolated porcine coronary artery. FASEB J., 19, 455 57. 

Machauer R, Waldmann H. Synthesis of the N-terminal N-myristoylated and S-palmitoylated undetrigintapeptide of endothelial NO-synthase. Angew. Chem. Int. Ed. 2000 39 1449-1453. 

Z. P. Chen, K. I. Mitchelhill, B. J. Michell, D. Stapleton, I. Rodriguez-Crespo, L. A. Witters, D. A. Power, P. R. Ortiz de Montellano and B. E. Kemp, AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett 443,285-289 (1999). 

Liu YH, Xu J, Yang XP, Yang F, Shesely E, Carretero OA. 2002. Effect of ACE inhibitors and angiotensin II type 1 receptor antagonists on endothelial NO synthase knockout mice with heart failure. Hypertension 39(2 Pt 2) 375—81... 

Kano H, Hayashi T, Sumi D, Esaki T, Asai Y, et al. 1999. A HMG-CoA reductase inhibitor improved regression of atherosclerosis in the rabbit aorta without affecting serum lipid levels possible relevance of up-regulation of endothelial NO synthase mRNA. Biochem. Biophys. Res. Commun. 259 414-19... 

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