Experts and Doctors on nitric oxide synthase in Boston, Massachusetts, United States


Locale: Boston, Massachusetts, United States
Topic: nitric oxide synthase

Top Publications

  1. Steudel W, Kirmse M, Weimann J, Ullrich R, Hromi J, Zapol W. Exhaled nitric oxide production by nitric oxide synthase-deficient mice. Am J Respir Crit Care Med. 2000;162:1262-7 pubmed
    ..Since NOS 2-deficient mice were the only genotype to lack substrate- and inhibitor-regulated changes of NO exhalation, we suggest that NOS 2 is an important isoform contributing to exhaled NO exhalation in healthy mice. ..
  2. 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
    ..These results demonstrate that HSP90 and Akt synergistically activate eNOS and suggest that this synergy contributes to Ca2+-independent eNOS activation in response to insulin. ..
  3. Michel J, Feron O, Sacks D, Michel T. Reciprocal regulation of endothelial nitric-oxide synthase by Ca2+-calmodulin and caveolin. J Biol Chem. 1997;272:15583-6 pubmed
    ..These findings may have broad implications for the regulation of Ca2+-dependent signal transduction in plasmalemmal caveolae. ..
  4. Feron O, Smith T, Michel T, Kelly R. Dynamic targeting of the agonist-stimulated m2 muscarinic acetylcholine receptor to caveolae in cardiac myocytes. J Biol Chem. 1997;272:17744-8 pubmed
    ..Thus, dynamic targeting of sarcolemmal m2 mAchR to caveolae following agonist binding may be essential to initiate specific downstream signaling cascades in these cells. ..
  5. Michel T, Feron O. Nitric oxide synthases: which, where, how, and why?. J Clin Invest. 1997;100:2146-52 pubmed
  6. Baron R, Carvajal I, Fredenburgh L, Liu X, Porrata Y, Cullivan M, et al. Nitric oxide synthase-2 down-regulates surfactant protein-B expression and enhances endotoxin-induced lung injury in mice. FASEB J. 2004;18:1276-8 pubmed
    ..This study demonstrates that expression of NOS2 in lung epithelial cells is critical for the development of lung injury and mediates surfactant dysfunction independent of NOS2 inflammatory cell expression and cytokine production...
  7. Frantz S, Kobzik L, Kim Y, Fukazawa R, Medzhitov R, Lee R, et al. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest. 1999;104:271-80 pubmed
    ..Increased expression and signaling by TLR4, and perhaps other Toll homologues, may contribute to the activation of innate immunity in injured myocardium. ..
  8. Buras J, Stahl G, Svoboda K, Reenstra W. Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am J Physiol Cell Physiol. 2000;278:C292-302 pubmed
    ..Our findings suggest that the beneficial effects of HBO in treating I/R injury may be mediated in part by inhibition of ICAM-1 expression through the induction of eNOS...
  9. Ullrich R, Bloch K, Ichinose F, Steudel W, Zapol W. Hypoxic pulmonary blood flow redistribution and arterial oxygenation in endotoxin-challenged NOS2-deficient mice. J Clin Invest. 1999;104:1421-9 pubmed

More Information


  1. Cambien B, Bergmeier W, Saffaripour S, Mitchell H, Wagner D. Antithrombotic activity of TNF-alpha. J Clin Invest. 2003;112:1589-96 pubmed
    ..This effect is not exerted directly on platelets but mediated through the rapid generation of NO in the vessel wall. ..
  2. Wechsler M, Grasemann H, Deykin A, Silverman E, Yandava C, Israel E, et al. Exhaled nitric oxide in patients with asthma: association with NOS1 genotype. Am J Respir Crit Care Med. 2000;162:2043-7 pubmed
  3. Kondo T, Vicent D, Suzuma K, Yanagisawa M, King G, Holzenberger M, et al. Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization. J Clin Invest. 2003;111:1835-42 pubmed
    ..These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process. ..
  4. 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
  5. Robinson L, Weremowicz S, Morton C, Michel T. Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics. 1994;19:350-7 pubmed
    ..abstract truncated at 250 words) ..
  6. Sugita H, Fujimoto M, Yasukawa T, Shimizu N, Sugita M, Yasuhara S, et al. Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem. 2005;280:14203-11 pubmed
    ..These findings indicate that iNOS reduces IRS-1 expression in skeletal muscle via proteasome-mediated degradation and thereby may contribute to obesity-related insulin resistance. ..
  7. Liu V, Huang P. Cardiovascular roles of nitric oxide: a review of insights from nitric oxide synthase gene disrupted mice. Cardiovasc Res. 2008;77:19-29 pubmed
    ..Mice lacking the inducible isoform show reduced hypotension to septic shock. Together, NOS gene knockout mice have been useful tools that complement our other approaches to studying the multiple roles of NO in the cardiovascular system. ..
  8. Milsom A, Fernandez B, Garcia Saura M, Rodriguez J, Feelisch M. Contributions of nitric oxide synthases, dietary nitrite/nitrate, and other sources to the formation of NO signaling products. Antioxid Redox Signal. 2012;17:422-32 pubmed publisher
  9. Igarashi J, Michel T. Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae. eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. J Biol Chem. 2000;275:32363-70 pubmed
    ..The agonist-modulated targeting of EDG-1 to caveolae and its dynamic inhibitory interactions with caveolin identify new points for regulation of sphingolipid-dependent signaling in the vascular wall. ..
  10. Kim C, Goyal R, Mashimo H. Neuronal NOS provides nitrergic inhibitory neurotransmitter in mouse lower esophageal sphincter. Am J Physiol. 1999;277:G280-4 pubmed
    ..These results indicate that in mouse LES, nNOS rather than eNOS is the enzymatic source of the NO that mediates NANC relaxation and rebound contraction. ..
  11. Klings E, Lowry M, Li G, Jean J, Fernandez B, Garcia Saura M, et al. Hyperoxia-induced lung injury in gamma-glutamyl transferase deficiency is associated with alterations in nitrosative and nitrative stress. Am J Pathol. 2009;175:2309-18 pubmed publisher
    ..Therefore, reduced denitrosylation of proteins, possibly resulting in impaired cellular repair, and excessive apoptotic cell death likely contribute to increased lung injury and mortality of GGT(enu1) mice in hyperoxia. ..
  12. Ichinose F, Zapol W, Sapirstein A, Ullrich R, Tager A, Coggins K, et al. Attenuation of hypoxic pulmonary vasoconstriction by endotoxemia requires 5-lipoxygenase in mice. Circ Res. 2001;88:832-8 pubmed
    ..Taken together, these findings demonstrate that a 5-LO product, most likely a cysteinyl LT, contributes to the attenuation of HPV and to pulmonary injury after challenge with endotoxin. ..
  13. Mannick J, Asano K, Izumi K, Kieff E, Stamler J. Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation. Cell. 1994;79:1137-46 pubmed
    ..These results suggest that NO plays a physiological role in human B cell biology by inhibiting programmed cell death and maintaining viral latency. ..
  14. Sugita H, Kaneki M, Tokunaga E, Sugita M, Koike C, Yasuhara S, et al. Inducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance. Am J Physiol Endocrinol Metab. 2002;282:E386-94 pubmed
    ..The protective effect of aminoguanidine on insulin resistance is probably by attenuation of hepatic glucose output via its inhibition of key enzymes for glycogenolysis and gluconeogenesis, including glycogen phosphorylase and PEPCK. ..
  15. Joussen A, Poulaki V, Mitsiades N, Kirchhof B, Koizumi K, Döhmen S, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J. 2002;16:438-40 pubmed
    ..Taken together, these data identify COX-2 and TNF-alpha as operative in the early signature pathologies of diabetic retinopathy, a newly recognized inflammatory disease...
  16. Park K, Kim J, Ahn Y, Bonventre A, Bonventre J. Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury. J Biol Chem. 2004;279:52282-92 pubmed
  17. Feron O, Dessy C, Opel D, Arstall M, Kelly R, Michel T. Modulation of the endothelial nitric-oxide synthase-caveolin interaction in cardiac myocytes. Implications for the autonomic regulation of heart rate. J Biol Chem. 1998;273:30249-54 pubmed
    ..Thus, our results suggest that acylated eNOS may couple muscarinic receptor activation to heart rate control and indicate a key role for eNOS/caveolin interactions in the cholinergic modulation of cardiac myocyte function. ..
  18. Jiang B, Xu S, Hou X, Pimentel D, Brecher P, Cohen R. Temporal control of NF-kappaB activation by ERK differentially regulates interleukin-1beta-induced gene expression. J Biol Chem. 2004;279:1323-9 pubmed
    ..These results reveal a novel functional role for ERK as an important temporal regulator of NF-kappaB activation and NF-kappaB-dependent gene expression. ..
  19. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004;279:1304-9 pubmed
    ..These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells. ..
  20. Chen Y, Layne M, Chung S, Ejima K, Baron R, Yet S, et al. Elk-3 is a transcriptional repressor of nitric-oxide synthase 2. J Biol Chem. 2003;278:39572-7 pubmed
    ..Thus, Elk-3 may serve as an important mediator of NOS2 gene expression. ..
  21. Munarriz R, Kim S, Kim N, Traish A, Goldstein I. A review of the physiology and pharmacology of peripheral (vaginal and clitoral) female genital arousal in the animal model. J Urol. 2003;170:S40-4; discussion S44-5 pubmed
    ..We review contemporary scientific data concerning the physiology and pharmacology of peripheral female genital arousal responses in the animal (rabbit and rat) model...
  22. Hampton T, Amende I, Fong J, Laubach V, Li J, Metais C, et al. Basic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused mouse hearts. Am J Physiol Heart Circ Physiol. 2000;279:H260-8 pubmed
    ..We conclude that basic FGF attenuates myocardial stunning independent of alterations in Ca(i)(2+) by stimulating NO production via an NOS2-dependent pathway...
  23. Park K, Metais C, Dai H, Comunale M, Sellke F. Microvascular endothelial dysfunction and its mechanism in a rat model of subarachnoid hemorrhage. Anesth Analg. 2001;92:990-6 pubmed
    ..This is in part related to decreased NOS3, which occurs despite an increase in its transcription. Acute microvascular endothelial dysfunction may occur after subarachnoid hemorrhage and contribute to microvascular spasm. ..
  24. 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. ..
  25. Makowski L, Brittingham K, Reynolds J, Suttles J, Hotamisligil G. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. J Biol Chem. 2005;280:12888-95 pubmed
    ..Our results demonstrate that aP2 regulates two central molecular pathways to coordinate macrophage cholesterol trafficking and inflammatory activity. ..
  26. Gonzalez E, Nagiel A, Lin A, Golan D, Michel T. Small interfering RNA-mediated down-regulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem. 2004;279:40659-69 pubmed
  27. Joussen A, Poulaki V, Tsujikawa A, Qin W, Qaum T, Xu Q, et al. Suppression of diabetic retinopathy with angiopoietin-1. Am J Pathol. 2002;160:1683-93 pubmed
    ..Taken together, these data document new vascular and anti-inflammatory bioactivities for angiopoietin-1 and identify it as the first naturally occurring protein that directly protects the retinal vasculature in diabetes. ..
  28. Lyons C, Orloff G, Cunningham J. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem. 1992;267:6370-4 pubmed
  29. Clavreul N, Adachi T, Pimental D, Ido Y, SCHONEICH C, Cohen R. S-glutathiolation by peroxynitrite of p21ras at cysteine-118 mediates its direct activation and downstream signaling in endothelial cells. FASEB J. 2006;20:518-20 pubmed
    ..These results indicate that peroxynitrite arising from NO donors or pathological stimuli such as oxLDL triggers direct S-glutathiolation of p21ras Cys-118, which increases p21ras activity and mediates downstream signaling. ..
  30. Erwin P, Lin A, Golan D, Michel T. Receptor-regulated dynamic S-nitrosylation of endothelial nitric-oxide synthase in vascular endothelial cells. J Biol Chem. 2005;280:19888-94 pubmed
    ..Taken together, these studies suggest that eNOS S-nitrosylation may represent an important mechanism for regulation of NO signaling pathways in the vascular wall. ..
  31. Yasukawa T, Tokunaga E, Ota H, Sugita H, Martyn J, Kaneki M. S-nitrosylation-dependent inactivation of Akt/protein kinase B in insulin resistance. J Biol Chem. 2005;280:7511-8 pubmed
    ..These data suggest that S-nitrosylation-mediated inactivation may contribute to the pathogenesis of iNOS- and/or oxidative stress-involved insulin resistance. ..
  32. Park K, Byun J, Kramers C, Kim J, Huang P, Bonventre J. Inducible nitric-oxide synthase is an important contributor to prolonged protective effects of ischemic preconditioning in the mouse kidney. J Biol Chem. 2003;278:27256-66 pubmed
  33. Rudders S, Gaspar J, Madore R, Voland C, Grall F, Patel A, et al. ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene. J Biol Chem. 2001;276:3302-9 pubmed
    ..Finally, in a mouse model of endotoxemia, associated with acute vascular inflammation, ESE-1 is strongly expressed in vascular endothelium and smooth muscle cells. In summary, ESE-1 represents a novel mediator of vascular inflammation. ..
  34. Chen M, Ona V, Li M, Ferrante R, Fink K, Zhu S, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000;6:797-801 pubmed
    ..In addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3 inhibition. This is the first demonstration of caspase-1 and caspase-3 transcriptional regulation in a Huntington disease model. ..
  35. Murohara T, Asahara T, Silver M, Bauters C, Masuda H, Kalka C, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest. 1998;101:2567-78 pubmed
  36. Guo L, Zhang Z, Green K, Stanton R. Suppression of interleukin-1 beta-induced nitric oxide production in RINm5F cells by inhibition of glucose-6-phosphate dehydrogenase. Biochemistry. 2002;41:14726-33 pubmed
    ..Also, inhibition of the cAMP-dependent PKA signal pathway is involved in an IL-1beta-stimulated increase in G6PD activity. ..
  37. Forgione M, Weiss N, Heydrick S, Cap A, Klings E, Bierl C, et al. Cellular glutathione peroxidase deficiency and endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2002;282:H1255-61 pubmed
    ..These vascular abnormalities can be attenuated by increasing bioavailable intracellular thiol pools. ..
  38. Ouchi N, Oshima Y, Ohashi K, Higuchi A, Ikegami C, Izumiya Y, et al. Follistatin-like 1, a secreted muscle protein, promotes endothelial cell function and revascularization in ischemic tissue through a nitric-oxide synthase-dependent mechanism. J Biol Chem. 2008;283:32802-11 pubmed publisher
  39. Feinberg M, Watanabe M, Lebedeva M, Depina A, Hanai J, Mammoto T, et al. Transforming growth factor-beta1 inhibition of vascular smooth muscle cell activation is mediated via Smad3. J Biol Chem. 2004;279:16388-93 pubmed
    ..Furthermore, we find that Smad3 prevents the cooperative induction of the iNOS promoter by C/EBP and NF-kappaB. These data demonstrate that Smad3 plays an essential role in mediating TGF-beta1 anti-inflammatory response in VSMCs. ..