endothelial nitric oxide synthase

Summary

Gene Symbol: endothelial nitric oxide synthase
Description: nitric oxide synthase 3
Alias: nitric oxide synthase, endothelial, EC-NOS, NOS type III, NOSIII, cNOS, constitutive NOS, eNOS, endothelial NOS, endothelial nitric oxide synthase, nitric oxide synthase 3 (endothelial cell)
Species: cow

Top Publications

  1. Stangl V, Lorenz M, Meiners S, Ludwig A, Bartsch C, Moobed M, et al. Long-term up-regulation of eNOS and improvement of endothelial function by inhibition of the ubiquitin-proteasome pathway. FASEB J. 2004;18:272-9 pubmed
    ..b>Endothelial nitric oxide synthase (eNOS) is the key enzyme of vascular homeostasis involved in the pathophysiology of several ..
  2. Iwakiri Y, Satoh A, Chatterjee S, Toomre D, Chalouni C, Fulton D, et al. Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking. Proc Natl Acad Sci U S A. 2006;103:19777-82 pubmed
    ..b>Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae...
  3. Xiao Z, Wang T, Qin H, Huang C, Feng Y, Xia Y. Endoplasmic reticulum Ca2+ release modulates endothelial nitric-oxide synthase via extracellular signal-regulated kinase (ERK) 1/2-mediated serine 635 phosphorylation. J Biol Chem. 2011;286:20100-8 pubmed publisher
    Endothelial nitric-oxide synthase (eNOS) plays a central role in cardiovascular regulation...
  4. Busconi L, Michel T. Endothelial nitric oxide synthase. N-terminal myristoylation determines subcellular localization. J Biol Chem. 1993;268:8410-3 pubmed
    ..N-terminal myristoylation of the endothelial NO synthase may provide a potential point of regulation of the biological functions of endothelium-derived NO in situ. ..
  5. Marchal S, Gorren A, Sørlie M, Andersson K, Mayer B, Lange R. Evidence of two distinct oxygen complexes of reduced endothelial nitric oxide synthase. J Biol Chem. 2004;279:19824-31 pubmed
    Oxygen binding to the oxygenase domain of reduced endothelial nitric oxide synthase (eNOS) results in two distinct species differing in their Soret and visible absorbance maxima and in their capacity to exchange oxygen by CO...
  6. Cooney R, Hynes S, Duffy A, Sharif F, O BRIEN T. Adenoviral-mediated gene transfer of nitric oxide synthase isoforms and vascular cell proliferation. J Vasc Res. 2006;43:462-72 pubmed
    ..our study was to compare the effects of adenoviral-mediated overexpression of the most commonly used NOS isoforms eNOS and iNOS on vascular cell proliferation...
  7. Sánchez F, Kim D, Duran R, Meininger C, Duran W. Internalization of eNOS via caveolae regulates PAF-induced inflammatory hyperpermeability to macromolecules. Am J Physiol Heart Circ Physiol. 2008;295:H1642-8 pubmed publisher
    Endothelial nitric oxide (NO) synthase (eNOS) is thought to regulate microvascular permeability via NO production...
  8. Tran Q, Leonard J, Black D, Persechini A. Phosphorylation within an autoinhibitory domain in endothelial nitric oxide synthase reduces the Ca(2+) concentrations required for calmodulin to bind and activate the enzyme. Biochemistry. 2008;47:7557-66 pubmed publisher
    ..phosphorylation at Ser-617 and Ser-635 within an autoinhibitory domain (residues 595-639) in bovine endothelial nitric oxide synthase on enzyme activity and the Ca (2+) dependencies for calmodulin binding and enzyme activation...
  9. Pires P, Santos N, Adona P, Natori M, Schwarz K, de Bem T, et al. Endothelial and inducible nitric oxide synthases in oocytes of cattle. Anim Reprod Sci. 2009;116:233-43 pubmed publisher
    ..The following experiments were performed: (1) detection of the endothelial (eNOS) and inducible (iNOS) isoforms in the ovary by immunohistochemistry; (2) detection of eNOS and iNOS in the oocytes ..

More Information

Publications92

  1. Li H, Raman C, Martasek P, Kral V, Masters B, Poulos T. Mapping the active site polarity in structures of endothelial nitric oxide synthase heme domain complexed with isothioureas. J Inorg Biochem. 2000;81:133-9 pubmed
    ..A small hydrophobic pocket in the active site is identified in the bovine eNOS heme domain structures complexed with potent isothiourea inhibitors: seleno analogue of S-ethyl-isothiourea, S-..
  2. Oubaha M, Gratton J. Phosphorylation of endothelial nitric oxide synthase by atypical PKC zeta contributes to angiopoietin-1-dependent inhibition of VEGF-induced endothelial permeability in vitro. Blood. 2009;114:3343-51 pubmed publisher
    ..Nitric oxide (NO) released from endothelial cells, after activation of endothelial NO synthase (eNOS), contributes to proangiogenic and permeability effects of VEGF...
  3. Gangopahyay A, Oran M, Bauer E, Wertz J, Comhair S, Erzurum S, et al. Bone morphogenetic protein receptor II is a novel mediator of endothelial nitric-oxide synthase activation. J Biol Chem. 2011;286:33134-40 pubmed publisher
    ..Endothelial dysfunction, including decreased endothelial nitric-oxide synthase (eNOS) activity and loss of bioactive nitric oxide (NO), plays a prominent role in the development of PAH...
  4. Cho D, Choi Y, Jo S, Nam J, Jung S, Jo I. Retinoic acid decreases nitric oxide production in endothelial cells: a role of phosphorylation of endothelial nitric oxide synthase at Ser(1179). Biochem Biophys Res Commun. 2005;326:703-10 pubmed
    ..has never been studied whether these effects are mediated by direct modulation of phosphorylation of endothelial nitric oxide synthase (eNOS)...
  5. Zemojtel T, Scheele J, Martasek P, Masters B, Sharma V, Magde D. Role of the interdomain linker probed by kinetics of CO ligation to an endothelial nitric oxide synthase mutant lacking the calmodulin binding peptide (residues 503-517 in bovine). Biochemistry. 2003;42:6500-6 pubmed
    ..the length of the interdomain linker in a deletion mutant lacking 15 amino acids (residues 503-517) in bovine eNOS. The kinetics of CO ligation with the mutant were determined in the presence and absence of tetrahydrobiopterin and ..
  6. Peng H, Zhuang Y, Harbeck M, He D, Xie L, Chen W. Serine 1179 Phosphorylation of Endothelial Nitric Oxide Synthase Increases Superoxide Generation and Alters Cofactor Regulation. PLoS ONE. 2015;10:e0142854 pubmed publisher
    b>Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. In addition to producing NO, eNOS can also generate superoxide (O2-...
  7. Nagane M, Yasui H, Sakai Y, Yamamori T, Niwa K, Hattori Y, et al. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway. Biochem Biophys Res Commun. 2015;456:541-6 pubmed publisher
    ..the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells...
  8. Su K, Shyue S, Kou Y, Ching L, Chiang A, Yu Y, et al. ? Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase. J Cell Physiol. 2011;226:3330-9 pubmed publisher
    ..We investigated the role of ?CR in EPO-induced endothelial NO synthase (eNOS) activation in bovine aortic ECs (BAECs) and the molecular mechanisms involved...
  9. Bulotta S, Barsacchi R, Rotiroti D, Borgese N, Clementi E. Activation of the endothelial nitric-oxide synthase by tumor necrosis factor-alpha. A novel feedback mechanism regulating cell death. J Biol Chem. 2001;276:6529-36 pubmed
    ..Our results identify a novel mechanism of regulation of a signal transduction pathway activated by death receptors and suggest that NO may constitute a built-in mechanism by which TNF-alpha controls its own apoptotic program. ..
  10. Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, et al. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science. 2003;299:896-9 pubmed
    ..mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS-/-) mice, which had a reduced metabolic rate and accelerated weight gain as ..
  11. Feng C, Taiakina V, Ghosh D, Guillemette J, Tollin G. Intraprotein electron transfer between the FMN and heme domains in endothelial nitric oxide synthase holoenzyme. Biochim Biophys Acta. 2011;1814:1997-2002 pubmed publisher
    ..J. Feng, G. Tollin, Dalton Trans., (2009) 6692-6700]. Here we report the kinetics of the IET in a bovine endothelial NOS (eNOS) holoenzyme in the presence and absence of added calmodulin (CaM)...
  12. Mukhopadhyay S, Xu F, Sehgal P. Aberrant cytoplasmic sequestration of eNOS in endothelial cells after monocrotaline, hypoxia, and senescence: live-cell caveolar and cytoplasmic NO imaging. Am J Physiol Heart Circ Physiol. 2007;292:H1373-89 pubmed
    ..this trafficking block affects subcellular localization and function of endothelial nitric oxide (NO) synthase (eNOS) and 2) whether Golgi blockade and eNOS sequestration are observed after hypoxia and senescence...
  13. Boo Y, Sorescu G, Bauer P, Fulton D, Kemp B, Harrison D, et al. Endothelial NO synthase phosphorylated at SER635 produces NO without requiring intracellular calcium increase. Free Radic Biol Med. 2003;35:729-41 pubmed
    ..We have shown that exposure of bovine aortic endothelial cells (BAEC) to shear stress stimulates phosphorylation of eNOS at S635 and S1179 by the protein kinase A- (PKA-) dependent mechanisms...
  14. Ching L, Kou Y, Shyue S, Su K, Wei J, Cheng L, et al. Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1. Cardiovasc Res. 2011;91:492-501 pubmed publisher
    ..a Ca(2+)-permeable non-selective cation channel, in the activation of endothelial nitric oxide (NO) synthase (eNOS) in endothelial cells (ECs) and mice. ..
  15. Takeda H, Komori K, Nishikimi N, Nimura Y, Sokabe M, Naruse K. Bi-phasic activation of eNOS in response to uni-axial cyclic stretch is mediated by differential mechanisms in BAECs. Life Sci. 2006;79:233-9 pubmed
    ..Correspondingly, the activities of endothelial nitric oxide synthase (eNOS) and Akt/PKB (measured by phosphorylation at serine 1,177 and serine 473, respectively), ..
  16. Zhou J, Abid M, Xiong Y, Chen Q, Chen J. ox-LDL downregulates eNOS activity via LOX-1-mediated endoplasmic reticulum stress. Int J Mol Med. 2013;32:1442-50 pubmed publisher
    ..in order to induce endoplasmic reticulum (ER) stress and to investigate the regulation of endothelial nitric oxide synthase (eNOS)...
  17. Tran J, Magenau A, Rodriguez M, Rentero C, Royo T, Enrich C, et al. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells. PLoS ONE. 2016;11:e0151556 pubmed publisher
    ..growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure...
  18. Connell P, Walshe T, Ferguson G, Gao W, O Brien C, Cahill P. Elevated glucose attenuates agonist- and flow-stimulated endothelial nitric oxide synthase activity in microvascular retinal endothelial cells. Endothelium. 2007;14:17-24 pubmed
    ..The aim of this study was to determine the effect of hyperglycemia on the expression of endothelial nitric oxide synthase (eNOS) and the release of nitric oxide (NO) in bovine microvascular retinal endothelial cells (BRECs)..
  19. Xu H, Shi Y, Wang J, Jones D, Weilrauch D, Ying R, et al. A heat shock protein 90 binding domain in endothelial nitric-oxide synthase influences enzyme function. J Biol Chem. 2007;282:37567-74 pubmed
    Previous reports suggest heat shock protein 90 (hsp90) associates with endothelial nitric-oxide synthase (eNOS) to increase nitric oxide (*NO) generation...
  20. Lin M, Fulton D, Babbitt R, Fleming I, Busse R, Pritchard K, et al. Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem. 2003;278:44719-26 pubmed
    There is evidence that endothelial nitric-oxide synthase (eNOS) is regulated by reciprocal dephosphorylation of Thr497 and phosphorylation of Ser1179...
  21. Salerno J, Ghosh D, Razdan R, Helms K, Brown C, McMurry J, et al. Endothelial nitric oxide synthase is regulated by ERK phosphorylation at Ser602. Biosci Rep. 2014;34: pubmed publisher
    eNOS (endothelial nitric oxide synthase) contains a MAPK (mitogen-activated protein kinase)-binding site associated with a major eNOS control element...
  22. Zhang M, Song P, Xu J, Zou M. Activation of NAD(P)H oxidases by thromboxane A2 receptor uncouples endothelial nitric oxide synthase. Arterioscler Thromb Vasc Biol. 2011;31:125-32 pubmed publisher
    ..IBOP also significantly suppressed activity of endothelial nitric oxide synthase (eNOS), increased enzyme-inactive eNOS monomers, and reduced levels of tetrahydrobiopterin, an ..
  23. Ramella R, Boero O, Alloatti G, Angelone T, Levi R, Gallo M. Vasostatin 1 activates eNOS in endothelial cells through a proteoglycan-dependent mechanism. J Cell Biochem. 2010;110:70-9 pubmed publisher
    ..However, the cellular processes upstream the eNOS activation exerted by this peptide are still unknown, as typical high-affinity receptors have not been identified...
  24. Bharath L, Cho J, Park S, Ruan T, Li Y, Mueller R, et al. Endothelial Cell Autophagy Maintains Shear Stress-Induced Nitric Oxide Generation via Glycolysis-Dependent Purinergic Signaling to Endothelial Nitric Oxide Synthase. Arterioscler Thromb Vasc Biol. 2017;37:1646-1656 pubmed publisher
    ..receptors, secondary to impaired autophagy in ECs, prevents shear-induced phosphorylation of eNOS (endothelial nitric oxide synthase) at its positive regulatory site S1117 (p-eNOSS1177) and NO generation...
  25. Kotsonis P, Fröhlich L, Raman C, Li H, Berg M, Gerwig R, et al. Structural basis for pterin antagonism in nitric-oxide synthase. Development of novel 4-oxo-pteridine antagonists of (6R)-5,6,7,8-tetrahydrobiopterin. J Biol Chem. 2001;276:49133-41 pubmed
    ..4-oxo compounds and, for comparisons an active 4-amino derivative, were then co-crystallized with the endothelial NOS (NOS-III) oxygenase domain and this structure solved to confirm the hypothetical binding modes...
  26. Bauer P, Fulton D, Boo Y, Sorescu G, Kemp B, Jo H, et al. Compensatory phosphorylation and protein-protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric-oxide synthase. J Biol Chem. 2003;278:14841-9 pubmed
    We examined the influence of individual serine phosphorylation sites in endothelial nitric-oxide synthase (eNOS) on basal and stimulated NO release, cooperative phosphorylation, and co-association with hsp90 and Akt...
  27. Mun G, Kim I, Lee B, Boo Y. Endothelial argininosuccinate synthetase 1 regulates nitric oxide production and monocyte adhesion under static and laminar shear stress conditions. J Biol Chem. 2011;286:2536-42 pubmed publisher
    ..The current study suggests that the expression of ASS1 harmonized with that of NOS3 may be important for the optimized endothelial NO production and the prevention of the inflammatory monocyte adhesion to endothelial cells. ..
  28. Hayashi K, Hosoe M, Takahashi T. Placental expression and localization of endothelin-1 system and nitric oxide synthases during bovine pregnancy. Anim Reprod Sci. 2012;134:150-7 pubmed publisher
    ..enzyme, EDNRA and EDNRB; receptor subtypes A and B) and endothelial and inducible nitric oxide synthases (eNOS and iNOS) in the bovine utero-placental unit during pregnancy...
  29. Greif D, Kou R, Michel T. Site-specific dephosphorylation of endothelial nitric oxide synthase by protein phosphatase 2A: evidence for crosstalk between phosphorylation sites. Biochemistry. 2002;41:15845-53 pubmed
    The endothelial isoform of nitric oxide synthase (eNOS) is a calcium/calmodulin-dependent enzyme that catalyzes the synthesis of nitric oxide, a key mediator of vascular homeostasis...
  30. Raman C, Li H, Martasek P, Southan G, Masters B, Poulos T. Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism. Biochemistry. 2001;40:13448-55 pubmed
    ..We report the crystal structure of the catalytic heme domain of endothelial NOS complexed with 7-NIBr at 1.65 A resolution...
  31. Youn J, Wang T, Cai H. An ezrin/calpain/PI3K/AMPK/eNOSs1179 signaling cascade mediating VEGF-dependent endothelial nitric oxide production. Circ Res. 2009;104:50-9 pubmed publisher
    ..AKT, AMP-dependent kinase (AMPK), and endothelial nitric oxide synthase (eNOS)(s1179) phosphorylations in VEGF-stimulated endothelial cells were markedly enhanced, which ..
  32. Suzuki H, Motley E, Eguchi K, Hinoki A, Shirai H, Watts V, et al. Distinct roles of protease-activated receptors in signal transduction regulation of endothelial nitric oxide synthase. Hypertension. 2009;53:182-8 pubmed publisher
  33. Bernatchez P, Bauer P, Yu J, Prendergast J, He P, Sessa W. Dissecting the molecular control of endothelial NO synthase by caveolin-1 using cell-permeable peptides. Proc Natl Acad Sci U S A. 2005;102:761-6 pubmed
    In endothelia, NO is synthesized by endothelial NO synthase (eNOS), which is negatively regulated by caveolin-1 (Cav-1), the primary coat protein of caveolae...
  34. Zhang Y, Lee T, Kolb E, Sun K, Lu X, Sladek F, et al. AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress. Arterioscler Thromb Vasc Biol. 2006;26:1281-7 pubmed
    ..protein kinase (AMPK) is implicated in vascular biology because AMPK can phosphorylate endothelial NO synthase (eNOS)...
  35. Matsubara M, Hayashi N, Jing T, Titani K. Regulation of endothelial nitric oxide synthase by protein kinase C. J Biochem. 2003;133:773-81 pubmed
    b>Endothelial nitric oxide synthase (eNOS) is a key enzyme in nitric oxide-mediated signal transduction in mammalian cells...
  36. Haque M, Ray S, Stuehr D. Phosphorylation Controls Endothelial Nitric-oxide Synthase by Regulating Its Conformational Dynamics. J Biol Chem. 2016;291:23047-23057 pubmed
    The activity of endothelial NO synthase (eNOS) is triggered by calmodulin (CaM) binding and is often further regulated by phosphorylation at several positions in the enzyme...
  37. Jobin C, Chen H, Lin A, Yacono P, Igarashi J, Michel T, et al. Receptor-regulated dynamic interaction between endothelial nitric oxide synthase and calmodulin revealed by fluorescence resonance energy transfer in living cells. Biochemistry. 2003;42:11716-25 pubmed
    The endothelial isoform of nitric oxide synthase (eNOS), a key regulator of vascular tone, is activated in endothelial cells by diverse Ca(2+)-mobilizing agonists, including vascular endothelial growth factor (VEGF)...
  38. Nishida K, Harrison D, Navas J, Fisher A, Dockery S, Uematsu M, et al. Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase. J Clin Invest. 1992;90:2092-6 pubmed
    ..The unique features of the endothelial cell NO synthase, particularly in the amino terminal portion of the molecule, may provide for novel regulatory influences of enzyme activity and localization. ..
  39. Raman C, Li H, Martasek P, Babu B, Griffith O, Masters B, et al. Implications for isoform-selective inhibitor design derived from the binding mode of bulky isothioureas to the heme domain of endothelial nitric-oxide synthase. J Biol Chem. 2001;276:26486-91 pubmed
    ..Isothioureas are potent NOS inhibitors, and the structures of the endothelial NOS heme domain complexed with isothioureas bearing small S-alkyl substituents have been determined (Li, H...
  40. Kou R, Michel T. Epinephrine regulation of the endothelial nitric-oxide synthase: roles of RAC1 and beta3-adrenergic receptors in endothelial NO signaling. J Biol Chem. 2007;282:32719-29 pubmed
    ..but the mechanisms whereby adrenergic pathways regulate the endothelial isoform of nitric-oxide synthase (eNOS) are incompletely understood...
  41. Martínez Moreno M, Alvarez Barrientos A, Roncal F, Albar J, Gavilanes F, Lamas S, et al. Direct interaction between the reductase domain of endothelial nitric oxide synthase and the ryanodine receptor. FEBS Lett. 2005;579:3159-63 pubmed
    We have performed the recombinant expression and purification of the reductase domain of endothelial nitric oxide synthase (eNOS) and used it as a bait in search for interacting proteins present in endothelial cells...
  42. Robinson L, Michel T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc Natl Acad Sci U S A. 1995;92:11776-80 pubmed
    The endothelial nitric oxide synthase (ec-NOS) plays a key role in the transduction of signals from the bloodstream to the underlying smooth muscle...
  43. Persechini A, Tran Q, Black D, Gogol E. Calmodulin-induced structural changes in endothelial nitric oxide synthase. FEBS Lett. 2013;587:297-301 pubmed publisher
    We have derived structures of intact calmodulin (CaM)-free and CaM-bound endothelial nitric oxide synthase (eNOS) by reconstruction from cryo-electron micrographs...
  44. Zhang Y, Chidiac R, Delisle C, Gratton J. Endothelial NO Synthase-Dependent S-Nitrosylation of ?-Catenin Prevents Its Association with TCF4 and Inhibits Proliferation of Endothelial Cells Stimulated by Wnt3a. Mol Cell Biol. 2017;37: pubmed publisher
    Nitric oxide (NO) produced by endothelial NO synthase (eNOS) modulates many functions in endothelial cells...
  45. Hess C, Kou R, Johnson R, Li G, Michel T. ADP signaling in vascular endothelial cells: ADP-dependent activation of the endothelial isoform of nitric-oxide synthase requires the expression but not the kinase activity of AMP-activated protein kinase. J Biol Chem. 2009;284:32209-24 pubmed publisher
    ..We found that ADP promoted phosphorylation of the endothelial isoform of nitric-oxide synthase (eNOS) at Ser(1179) and Ser(635) and dephosphorylation at Ser(116) in cultured endothelial cells...
  46. Trane A, Pavlov D, Sharma A, Saqib U, Lau K, Van Petegem F, et al. Deciphering the binding of caveolin-1 to client protein endothelial nitric-oxide synthase (eNOS): scaffolding subdomain identification, interaction modeling, and biological significance. J Biol Chem. 2014;289:13273-83 pubmed publisher
    ..Recent evidence suggests that blunted Cav-1/endothelial nitric-oxide synthase (eNOS) interaction, which occurs specifically in vascular endothelial cells, is responsible for the multiple phenotypes ..
  47. Averna M, Stifanese R, De Tullio R, Passalacqua M, Salamino F, Pontremoli S, et al. Functional role of HSP90 complexes with endothelial nitric-oxide synthase (eNOS) and calpain on nitric oxide generation in endothelial cells. J Biol Chem. 2008;283:29069-76 pubmed publisher
    Although several reports have indicated that eNOS is a highly sensitive calpain substrate, the occurrence of a concomitant Ca(2+)-dependent activation of the synthase and of the protease has never been analyzed in specific direct ..
  48. Zamberlam G, Sahmi F, Price C. Nitric oxide synthase activity is critical for the preovulatory epidermal growth factor-like cascade induced by luteinizing hormone in bovine granulosa cells. Free Radic Biol Med. 2014;74:237-44 pubmed publisher
    ..Time- and dose-response experiments demonstrated that LH had a significant stimulatory effect on endothelial NOS (NOS3) mRNA abundance, but in a prostaglandin-dependent manner...
  49. Ou J, Ou Z, Ackerman A, Oldham K, Pritchard K. Inhibition of heat shock protein 90 (hsp90) in proliferating endothelial cells uncouples endothelial nitric oxide synthase activity. Free Radic Biol Med. 2003;34:269-76 pubmed
    ..Increased expression of endothelial nitric oxide synthase (eNOS) has been shown to play an important role in maintaining high levels of (*)NO generation to ..
  50. Goodwin B, Pendleton L, Levy M, Solomonson L, Eichler D. Tumor necrosis factor-alpha reduces argininosuccinate synthase expression and nitric oxide production in aortic endothelial cells. Am J Physiol Heart Circ Physiol. 2007;293:H1115-21 pubmed
    ..Cellular NO production depends absolutely on the availability of arginine, substrate of endothelial nitric oxide synthase (eNOS)...
  51. Arnett D, Persechini A, Tran Q, Black D, Johnson C. Fluorescence quenching studies of structure and dynamics in calmodulin-eNOS complexes. FEBS Lett. 2015;589:1173-8 pubmed publisher
    Activation of endothelial nitric oxide synthase (eNOS) by calmodulin (CaM) facilitates formation of a sequence of conformational states that is not well understood...
  52. Anderson H, Rahmutula D, Gardner D. Tumor necrosis factor-alpha inhibits endothelial nitric-oxide synthase gene promoter activity in bovine aortic endothelial cells. J Biol Chem. 2004;279:963-9 pubmed
    Tumor necrosis factor-alpha (TNF-alpha) has been shown to reduce endothelial nitric-oxide synthase (eNOS) gene expression through post-transcriptional regulation of mRNA stability...
  53. Chen Y, Medhora M, Falck J, Pritchard K, Jacobs E. Mechanisms of activation of eNOS by 20-HETE and VEGF in bovine pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2006;291:L378-85 pubmed
    ..dilation of bovine pulmonary arteries is associated with activation of cytochrome P-450 family 4 (CYP4) enzymes and eNOS. We hypothesized that VEGF and the CYP4 product 20-HETE would trigger common downstream pathways of intracellular ..
  54. Jackson S, Venema R. Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. J Nutr. 2006;136:1178-84 pubmed
    ..the first evidence that QRN inhibits angiogenesis via a mechanism involving both suppression of endothelial nitric oxide synthase (eNOS) and early M-phase cell cycle arrest...
  55. Sugimoto M, Nakayama M, Goto T, Amano M, Komori K, Kaibuchi K. Rho-kinase phosphorylates eNOS at threonine 495 in endothelial cells. Biochem Biophys Res Commun. 2007;361:462-7 pubmed
    b>Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), which is involved in various physiological functions of the cardiovascular system. eNOS is activated by dephosphorylation at Thr495 and phosphorylation at Ser1177...
  56. Sánchez F, Rana R, Kim D, Iwahashi T, Zheng R, Lal B, et al. Internalization of eNOS and NO delivery to subcellular targets determine agonist-induced hyperpermeability. Proc Natl Acad Sci U S A. 2009;106:6849-53 pubmed publisher
    The molecular mechanisms of endothelial nitric oxide synthase (eNOS) regulation of microvascular permeability remain unresolved. Agonist-induced internalization may have a role in this process...
  57. Sessa W, Harrison J, Barber C, Zeng D, Durieux M, D Angelo D, et al. Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase. J Biol Chem. 1992;267:15274-6 pubmed
    ..In addition, ECNOS contains a unique N-myristylation consensus sequence (not shared by bNOS or Mac-NOS) that may explain its membrane localization. ..
  58. Jones S, Greer J, Kakkar A, Ware P, Turnage R, Hicks M, et al. Endothelial nitric oxide synthase overexpression attenuates myocardial reperfusion injury. Am J Physiol Heart Circ Physiol. 2004;286:H276-82 pubmed
    Previous studies indicate that deficiency of endothelial nitric oxide (NO) synthase (eNOS)-derived NO exacerbates myocardial reperfusion injury...
  59. Monti M, Donnini S, Giachetti A, Mochly Rosen D, Ziche M. deltaPKC inhibition or varepsilonPKC activation repairs endothelial vascular dysfunction by regulating eNOS post-translational modification. J Mol Cell Cardiol. 2010;48:746-56 pubmed publisher
    The balance between endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) and reactive oxygen species (ROS) production determines endothelial-mediated vascular homeostasis...
  60. Venema R, Venema V, Ju H, Harris M, Snead C, Jilling T, et al. Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. Am J Physiol Heart Circ Physiol. 2003;285:H669-78 pubmed
    ..is an important downstream intracellular target of nitric oxide (NO) that is produced by endothelial NO synthase (eNOS) and inducible NO synthase (iNOS)...
  61. Presley T, Vedam K, Velayutham M, Zweier J, Ilangovan G. Activation of Hsp90-eNOS and increased NO generation attenuate respiration of hypoxia-treated endothelial cells. Am J Physiol Cell Physiol. 2008;295:C1281-91 pubmed publisher
    ..respiration by a mechanism involving heat shock protein 90 (Hsp90) and endothelial nitric oxide (NO) synthase (eNOS), so that the cells are conditioned to consume less oxygen and survive in prolonged hypoxic conditions...
  62. Vilahur G, Padró T, Casaní L, Mendieta G, López J, Streitenberger S, et al. Polyphenol-enriched diet prevents coronary endothelial dysfunction by activating the Akt/eNOS pathway. Rev Esp Cardiol (Engl Ed). 2015;68:216-25 pubmed publisher
    ..Pomanox supplementation hinders hyperlipemia-induced coronary endothelial dysfunction by activating the Akt/endothelial nitric oxide-synthase pathway and favorably counteracting vascular inflammation and oxidative damage. ..
  63. Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, et al. Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol. 2006;2:596-607 pubmed
    ..These findings reveal the structural motif for the NO-sensitive activation gate in TRP channels and indicate that NO sensors are a new functional category of cellular receptors extending over different TRP families. ..
  64. Shirasuna K, Asahi T, Sasaki M, Shimizu T, Miyamoto A. Distribution of arteriolovenous vessels, capillaries and eNOS expression in the bovine corpus luteum during the estrous cycle: a possible implication of different sensitivity by luteal phase to PGF(2alpha) in the increase of luteal blood flow. J Reprod Dev. 2010;56:124-30 pubmed
    ..In the present study, we characterized the CL vasculature together with endothelial NO synthase (eNOS) expression during the estrous cycle in the cow...
  65. Cao S, Yao J, Shah V. The proline-rich domain of dynamin-2 is responsible for dynamin-dependent in vitro potentiation of endothelial nitric-oxide synthase activity via selective effects on reductase domain function. J Biol Chem. 2003;278:5894-901 pubmed
    ..dyn-2) binds and positively regulates the nitric oxide-generating enzyme, endothelial nitric-oxide synthase (eNOS) (Cao, S., Yao, Y., McCabe, T., Yao, Q., Katusic, Z., Sessa, W., and Shah, V. (2001) J. Biol. Chem...
  66. Takahashi S, Mendelsohn M. Synergistic activation of endothelial nitric-oxide synthase (eNOS) by HSP90 and Akt: calcium-independent eNOS activation involves formation of an HSP90-Akt-CaM-bound eNOS complex. J Biol Chem. 2003;278:30821-7 pubmed
    Endothelial nitric-oxide synthase (eNOS), which generates the endogenous vasodilator, nitric oxide (NO), is highly regulated by post-translational modifications and protein interactions...
  67. Tessaro I, Luciano A, Franciosi F, Lodde V, Corbani D, Modina S. The endothelial nitric oxide synthase/nitric oxide system is involved in the defective quality of bovine oocytes from low mid-antral follicle count ovaries. J Anim Sci. 2011;89:2389-96 pubmed publisher
    ..The aim of the present study was to evaluate whether a defective endothelial nitric oxide synthase/nitric oxide (eNOS/NO) system and vasculature in healthy medium antral follicles is likely to reduce ..
  68. Ebong E, Lopez Quintero S, Rizzo V, Spray D, Tarbell J. Shear-induced endothelial NOS activation and remodeling via heparan sulfate, glypican-1, and syndecan-1. Integr Biol (Camb). 2014;6:338-47 pubmed publisher
    ..We hypothesized that the glypican-1 (GPC1) HS core protein mediates flow-induced EC NO synthase (eNOS) activation because GPC1 is anchored to caveolae where eNOS resides...
  69. Jin Z, Wong C, Wu J, Berk B. Flow shear stress stimulates Gab1 tyrosine phosphorylation to mediate protein kinase B and endothelial nitric-oxide synthase activation in endothelial cells. J Biol Chem. 2005;280:12305-9 pubmed
    ..that flow activated the phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric-oxide synthase (eNOS) via Src kinase-dependent transactivation of vascular endothelial growth factor receptor 2 (VEGFR2)...
  70. Haines R, Corbin K, Pendleton L, Eichler D. Protein kinase C? phosphorylates a novel argininosuccinate synthase site at serine 328 during calcium-dependent stimulation of endothelial nitric-oxide synthase in vascular endothelial cells. J Biol Chem. 2012;287:26168-76 pubmed publisher
    Endothelial nitric-oxide synthase (eNOS) utilizes l-arginine as its principal substrate, converting it to l-citrulline and nitric oxide (NO)...
  71. Lamas S, Marsden P, Li G, Tempst P, Michel T. Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci U S A. 1992;89:6348-52 pubmed
    ..The increase in BAEC NO synthase activity induced by tumor necrosis factor alpha is thus likely to involve posttranscriptional mechanisms or the induction of a distinct endothelial NO synthase isoform. ..
  72. Watanabe T, Suzuki J, Yamawaki H, Sharma V, Sheu S, Berk B. Losartan metabolite EXP3179 activates Akt and endothelial nitric oxide synthase via vascular endothelial growth factor receptor-2 in endothelial cells: angiotensin II type 1 receptor-independent effects of EXP3179. Circulation. 2005;112:1798-805 pubmed
    ..Because of the importance of endothelial nitric oxide synthase (eNOS) in vascular and platelet function, we hypothesized that losartan and its metabolites would ..
  73. Li H, Raman C, Martasek P, Masters B, Poulos T. Crystallographic studies on endothelial nitric oxide synthase complexed with nitric oxide and mechanism-based inhibitors. Biochemistry. 2001;40:5399-406 pubmed
    The crystal structure of the endothelial nitric oxide synthase (NOS) heme domain complexed with NO reveals close hydrogen bonding interactions between NO and the terminal guanidino nitrogen of the substrate, L-arginine...
  74. Li C, Huang W, Harris M, Goolsby J, Venema R. Interaction of the endothelial nitric oxide synthase with the CAT-1 arginine transporter enhances NO release by a mechanism not involving arginine transport. Biochem J. 2005;386:567-74 pubmed
    eNOS (endothelial nitric oxide synthase) catalyses the conversion of L-arginine into L-citrulline and NO...
  75. Ishikawa T, Kondo Y, Goda K, Fujisawa M. Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism. J Androl. 2005;26:281-8 pubmed
    ..The objective of this study was to investigate whether overexpression of endothelial NO synthase (eNOS) could accelerate apoptosis of germ cells in the testes of transgenic mice...
  76. Volkmann N, Martásek P, Roman L, Xu X, Page C, Swift M, et al. Holoenzyme structures of endothelial nitric oxide synthase - an allosteric role for calmodulin in pivoting the FMN domain for electron transfer. J Struct Biol. 2014;188:46-54 pubmed publisher
    ..Application of electron cryo-microscopy and structural modeling of the bovine endothelial nitric oxide synthase (eNOS) holoenzyme produced detailed models of the intact holoenzyme in the presence and absence of ..
  77. Tran Q, Leonard J, Black D, Nadeau O, Boulatnikov I, Persechini A. Effects of combined phosphorylation at Ser-617 and Ser-1179 in endothelial nitric-oxide synthase on EC50(Ca2+) values for calmodulin binding and enzyme activation. J Biol Chem. 2009;284:11892-9 pubmed publisher
    ..Changes in the biochemical properties of eNOS produced by combined phosphorylation at Ser-617 and Ser-1179 are predicted to substantially increase synthase ..
  78. Kosmidou I, Moore J, Weber M, Searles C. Statin treatment and 3' polyadenylation of eNOS mRNA. Arterioscler Thromb Vasc Biol. 2007;27:2642-9 pubmed
    Statins have been shown to increase endothelial nitric oxide synthase expression via enhanced mRNA stability...
  79. Park J, Park M, Byun C, Jo I. c-Jun N-terminal kinase 2 phosphorylates endothelial nitric oxide synthase at serine 116 and regulates nitric oxide production. Biochem Biophys Res Commun. 2012;417:340-5 pubmed publisher
    ..decreased nitric oxide (NO) production via decreased phosphorylation of endothelial NO synthase at serine 1179 (eNOS-Ser(1179)) was reported to be partly involved in JNK2-derived endothelial dysfunction, JNK2 seems likely to be ..
  80. Ching L, Zhao J, Su K, Shyue S, Hsu C, Lu T, et al. Activation of transient receptor potential vanilloid 1 decreases endothelial nitric oxide synthase phosphorylation at Thr497 by protein phosphatase 2B-dependent dephosphorylation of protein kinase C. Acta Physiol (Oxf). 2013;209:124-35 pubmed publisher
    ..1 (TRPV1), a calcium (Ca(2+) )-permeable non-selective cation channel, on phosphorylation of endothelial nitric oxide synthase (eNOS) at threonine 497 (Thr497) in bovine aortic endothelial cells (BAECs) and in mice. ..
  81. Pi X, Wu Y, Ferguson J, Portbury A, Patterson C. SDF-1alpha stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration. Proc Natl Acad Sci U S A. 2009;106:5675-80 pubmed publisher
    ..we describe the identification of an intricate SDF-1alpha-induced signaling cascade that involves endothelial nitric oxide synthase (eNOS), JNK3, and MAPK phosphatase 7 (MKP7)...
  82. Namba T, Koike H, Murakami K, Aoki M, Makino H, Hashiya N, et al. Angiogenesis induced by endothelial nitric oxide synthase gene through vascular endothelial growth factor expression in a rat hindlimb ischemia model. Circulation. 2003;108:2250-7 pubmed
    ..on the role of vascular endothelial growth factor (VEGF) in angiogenesis induced by endothelial NO synthase (eNOS) gene transfer...
  83. Fulton D, Church J, Ruan L, Li C, Sood S, Kemp B, et al. Src kinase activates endothelial nitric-oxide synthase by phosphorylating Tyr-83. J Biol Chem. 2005;280:35943-52 pubmed
    The endothelial nitric-oxide synthase (eNOS) is regulated in part by serine/threonine phosphorylation, but eNOS tyrosine phosphorylation is less well understood...