Nitric oxide synthase cells

MacMicking, J.D. et al., Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase, Cell, 81, 641, 1995. 

Ghafourifar P, Saavedra-Molina A. Functions of mitochondrial nitric oxide synthase. Oxidative Stress and Disease 2006 19 77-98. Su Y, Kondrikov D, Block ER. Cytoskeletal regulation of nitric oxide synthase. Cell Biochem. Biophys. 2005 43(3) 439-449. Hobbs AJ, Higgs A, Moncada S. Inhibition of nitric oxide synthase as a potential therapeutic target. Annu. Rev. Pharmacol. Toxicol. 1999 39 191-220. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Schaefer U, Schneider A, Rixen D, Neugebauer E (1998) Neutrophil adhesion to histamine stimulated cultured endothelial cells is primarily mediated via activation of phospholipase C and nitric oxide synthase isozymes. Inflamm Res 47(6) 256-264 Schaefer U, Schmitz V, Schneider A, Neugebauer E (1999) Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial ceUs. Shock 12(4) 309-315... 

Nitric oxide has also been implicated in PD. Thus animals with MPTP-induced Parkinsonism not only show extensive gliosis in the substantia nigra (like humans) in which the glial cells produce NO, but Liberatore and colleagues have found that in iNOS (inducible nitric oxide synthase) knock-out mice the toxicity of MPTP is halved. Since NO releases iron from ferritin and produces toxic peroxinitrate in the presence of superoxide radicals it could accelerate, even if it does not initiate, dopaminergic cell death (see Hirsch and Hunot 2000 for further details). 

Radomski, M.W., Palmer, R.M. and Moncada, S. (1990). Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc. Natl Acad. Sci. USA 87, 10043-10047. 

Hong CH, Sun KH, Jin O, Sun SK, Kyung AN, Sang KL. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J Ethnopharmacol 2002 83 153-159. 

Rafi, MM and Shafaie, Y, 2007. Dietary lutein modulates inducible nitric oxide synthase (iNOS) gene and protein expression in mouse macrophage cells (RAW 264.7). Mol Nutr Food Res 51, 333-340. 

Sakata K, Hirose Y, Qiao Z, Tanaka T and Mori H. 2003. Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett 199(2)439-145. 

Marlett, M. Nitric oxide synthase aspects concerning structure and catalysts. Cell 78 927-930,1994. 

FIGURE 34-5 Induction of endothelial nitric oxide synthase (eNOS) in medial thalamus of thiamine-deficient rats. (A) Increased eNOS mRNA. (B) Increased eNOS immunolabeling of vascular endothelial cells (magnification x200). 

The interaction of estrogen receptors with signaling systems of the cell membrane that respond to growth factors and mediate nongenomic, fast actions of estrogens will be reviewed as well. These mechanisms have a growing importance in the comprehension of phenomena like the induction of endothelial NOS (nitric oxide synthase) by estrogens (Rubanyi et al. 2002). 

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Simoncini T, Genazzani AR (2000) Raloxifene acutely stimulates nitric oxide release from human endothelial cells via an activation of endothelial nitric oxide synthase. J Clin Endocrinol Metab 85(8) 2966-2969... 

Exposure to trichothecenes at levels that partially inhibit translation upregulates expression of many inflammatory and immune-related genes including macrophage, Thl and Th2 cytokines as well as chemokines, cyclooxygenase 2 and inducible nitric oxide synthase.1518 Contrastingly, suppressive effects of trichothecenes on leukocyte function are intimately linked with the induction of apoptosis as has been demonstrated in macrophages, T cells and B cells both in vivo and in vitro.19-20... 

Kleeberger, S.R., et al., Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase, Am. J. Physiol. Lung. Cell. Mol. Physiol. 280, 2,L326, 2001. 

Kiselyov K, Mignery GA, Zhu MX, Muallem S 1999 The N-terminal domain of the IP3 receptor gates store-operated hTrp3 channels. Mol Cell 4 423-429 Lee HC 2000 NAADP An emerging calcium signaling molecule. J Membr Biol 173 1 -8 Lin S, Fagan KA, Li K-X, Shaul PW, Cooper DMF, Rodman DM 2000 Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J Biol Chem 275 17979-17985... 

Marczin N, Jilling T, Papapetropoulos A, Go C, Catravas JD 1996 Cytoskeleton-dependent activation of the inducible nitric oxide synthase in cultured aortic smooth muscle cells. Br J Pharmacol 118 1085—1094... 

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