Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1255-1261
© 1995 American Heart Association, Inc.
Articles |
Molecular Regulation of the Bovine Endothelial Cell Nitric Oxide Synthase by Transforming Growth Factor–ß1
From the Departments of Medicine and Pharmacology, Emory University School of Medicine, and the Atlanta Veterans Administration Medical Center, Atlanta, Ga.
Correspondence to David G. Harrison, MD, Cardiology Division, PO Box LL, Emory University School of Medicine, Atlanta, GA 30322.
Abstract The promoter region of the endothelial cell nitric oxide synthase (ecNOS) gene contains potential response elements for transforming growth factor–ß1 (TGFß1). TGFß1 plays an important role in the pathogenesis of atherosclerosis, vascular hypertrophy, and angiogenesis. We therefore sought to determine whether TGFß1 might modulate ecNOS expression in bovine aortic endothelial cells (BAEC). TGFß1 increased ecNOS mRNA in a dose-dependent manner. TGFß1 also increased ecNOS protein content. The production of nitrogen oxides (NOx), assessed by chemiluminescence, and nitric oxide synthase activity, assessed by arginine/citrulline conversion, were increased in TGFß1-treated cells. Transcriptional activity of the 5'-flanking promoter region of the ecNOS gene was increased by TGFß1, as assessed by transfection with promoter/luciferase constructs. Deletion analysis suggested that the TGFß1-response element was present between nucleotides -1269 and -935 from the first transcription start site, in which a putative nuclear factor–1 (NF-1) binding site existed. Gel shift assays showed that nuclear protein(s), immunologically similar to CCAAT transcription factor/NF-1, bound to the putative NF-1 binding site in a sequence-specific manner. Mutation of the putative NF-1 binding site in the promoter/luciferase construct significantly decreased the responsiveness to TGFß1. In conclusion, TGFß1 increases ecNOS expression associated with an increase in production of NO in BAEC. This response is probably mediated by transcriptional activation of the ecNOS gene promoter.
Key Words: nitric oxide synthase • transforming growth factor–ß1 • endothelium • nuclear factor–1
This article has been cited by other articles:
 |
|
 |
|
  V. C. Sandrim, A. C.T. Palei, I. F. Metzger, V. A. Gomes, R. C. Cavalli, and J. E. Tanus-Santos Nitric Oxide Formation Is Inversely Related to Serum Levels of Antiangiogenic Factors Soluble Fms-Like Tyrosine Kinase-1 and Soluble Endogline in Preeclampsia Hypertension, August 1, 2008; 52(2): 402 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. V. Ingman and S. A. Robertson Transforming Growth Factor-{beta}1 Null Mutation Causes Infertility in Male Mice Associated with Testosterone Deficiency and Sexual Dysfunction Endocrinology, August 1, 2007; 148(8): 4032 - 4043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Searles Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression Am J Physiol Cell Physiol, November 1, 2006; 291(5): C803 - C816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N.N. Han, S. Babaei, M. Robb, T. Lee, R. Ridsdale, C. Ackerley, M. Post, and D. J. Stewart Defective Lung Vascular Development and Fatal Respiratory Distress in Endothelial NO Synthase-Deficient Mice: A Model of Alveolar Capillary Dysplasia? Circ. Res., April 30, 2004; 94(8): 1115 - 1123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Baldwin, L. Pirisi, and K. E. Creek NFI-Ski Interactions Mediate Transforming Growth Factor {beta} Modulation of Human Papillomavirus Type 16 Early Gene Expression J. Virol., April 15, 2004; 78(8): 3953 - 3964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Tai, G. B. Robb, and P. A. Marsden Endothelial Nitric Oxide Synthase: A New Paradigm for Gene Regulation in the Injured Blood Vessel Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 405 - 412. [Abstract] [Full Text]
|
|
|
|
|
|
P. W. Sanders Salt Intake, Endothelial Cell Signaling, and Progression of Kidney Disease Hypertension, February 1, 2004; 43(2): 142 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Beck, R. Xavier, J. Wong, I. Ezedi, H. Mashimo, A. Mizoguchi, E. Mizoguchi, A. K. Bhan, and D. K. Podolsky Paradoxical roles of different nitric oxide synthase isoforms in colonic injury Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G137 - G147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benigni, C. Zoja, D. Corna, C. Zatelli, S. Conti, M. Campana, E. Gagliardini, D. Rottoli, C. Zanchi, M. Abbate, et al. Add-On Anti-TGF-{beta} Antibody to ACE Inhibitor Arrests Progressive Diabetic Nephropathy in the Rat J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1816 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Komers and S. Anderson Paradoxes of nitric oxide in the diabetic kidney Am J Physiol Renal Physiol, June 1, 2003; 284(6): F1121 - F1137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Babaei, K. Teichert-Kuliszewska, Q. Zhang, N. Jones, D. J. Dumont, and D. J. Stewart Angiogenic Actions of Angiopoietin-1 Require Endothelium-Derived Nitric Oxide Am. J. Pathol., June 1, 2003; 162(6): 1927 - 1936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saura, C. Zaragoza, W. Cao, C. Bao, M. Rodriguez-Puyol, D. Rodriguez-Puyol, and C. J. Lowenstein Smad2 Mediates Transforming Growth Factor-{beta} Induction of Endothelial Nitric Oxide Synthase Expression Circ. Res., November 1, 2002; 91(9): 806 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rossig, H. Li, B. Fisslthaler, C. Urbich, I. Fleming, U. Forstermann, A. M. Zeiher, and S. Dimmeler Inhibitors of Histone Deacetylation Downregulate the Expression of Endothelial Nitric Oxide Synthase and Compromise Endothelial Cell Function in Vasorelaxation and Angiogenesis Circ. Res., November 1, 2002; 91(9): 837 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Dahly, K. M. Hoagland, A. K. Flasch, S. Jha, S. R. Ledbetter, and R. J. Roman Antihypertensive effects of chronic anti-TGF-beta antibody therapy in Dahl S rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R757 - R767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Cooke and D. W. Losordo Nitric Oxide and Angiogenesis Circulation, May 7, 2002; 105(18): 2133 - 2135. [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Tuttle, R. D. Nachreiner, A. S. Bhuller, K. W. Condict, B. A. Connors, B. P. Herring, M. C. Dalsing, and J. L. Unthank Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1380 - H1389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C Kone Molecular biology of natriuretic peptides and nitric oxide synthases Cardiovasc Res, August 15, 2001; 51(3): 429 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Govers and T. J. Rabelink Cellular regulation of endothelial nitric oxide synthase Am J Physiol Renal Physiol, February 1, 2001; 280(2): F193 - F206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Jang, H.-K. V. Ho, H. H. Kwan, L. F. Fajardo, and J. P. Cooke Angiogenesis Is Impaired by Hypercholesterolemia : Role of Asymmetric Dimethylarginine Circulation, September 19, 2000; 102(12): 1414 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. I Romero, D.-N. Zhang, J. P Cooke, H.-K. V Ho, E. Avalos, R. Herrera, and G S. Herron Differential expression of nitric oxide by dermal microvascular endothelial cells from patients with scleroderma Vascular Medicine, August 1, 2000; 5(3): 147 - 158. [Abstract] [PDF]
|
|
|
|
|
|
G. Draude and R. L. Lorenz TGF-beta 1 downregulates CD36 and scavenger receptor A but upregulates LOX-1 in human macrophages Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1042 - H1048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Drummond, H. Cai, M. E. Davis, S. Ramasamy, and D. G. Harrison Transcriptional and Posttranscriptional Regulation of Endothelial Nitric Oxide Synthase Expression by Hydrogen Peroxide Circ. Res., February 18, 2000; 86(3): 347 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Navarro-Antolin, J. Rey-Campos, and S. Lamas Transcriptional Induction of Endothelial Nitric Oxide Gene by Cyclosporine A. A ROLE FOR ACTIVATOR PROTEIN-1 J. Biol. Chem., February 4, 2000; 275(5): 3075 - 3080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Whitney, Z. German, T. S. Sherman, I. S. Yuhanna, and P. W. Shaul Cell growth modulates nitric oxide synthase expression in fetal pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L131 - L138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Yuhanna, A. N. MacRitchie, R. L. Lantin-Hermoso, L. B. Wells, and P. W. Shaul Nitric Oxide (NO) Upregulates NO Synthase Expression in Fetal Intrapulmonary Artery Endothelial Cells Am. J. Respir. Cell Mol. Biol., November 1, 1999; 21(5): 629 - 636. [Abstract] [Full Text]
|
|
|
|
|
|
W.-Z. Ying and P. W. Sanders Dietary salt increases endothelial nitric oxide synthase and TGF-beta 1 in rat aortic endothelium Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1293 - H1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Papapetropoulos, R. D. Rudic, and W. C Sessa Molecular control of nitric oxide synthases in the cardiovascular system Cardiovasc Res, August 15, 1999; 43(3): 509 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Linz, P. Wohlfart, B. A Scholkens, T. Malinski, and G. Wiemer Interactions among ACE, kinins and NO Cardiovasc Res, August 15, 1999; 43(3): 549 - 561. [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Jeremy, D. Rowe, A. M. Emsley, and A. C. Newby Nitric oxide and the proliferation of vascular smooth muscle cells Cardiovasc Res, August 15, 1999; 43(3): 580 - 594. [Full Text] [PDF]
|
|
|
|
|
|
T. E. Peterson, V. Poppa, H. Ueba, A. Wu, C. Yan, and B. C. Berk Opposing Effects of Reactive Oxygen Species and Cholesterol on Endothelial Nitric Oxide Synthase and Endothelial Cell Caveolae Circ. Res., July 9, 1999; 85(1): 29 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mortensen, S. Holck, I. J. Christensen, J. Skouv, D. M. Hougaard, J. Blom, and L.-I. Larsson Endothelial Cell Nitric Oxide Synthase in Peritumoral Microvessels Is a Favorable Prognostic Indicator in Premenopausal Breast Cancer Patients Clin. Cancer Res., May 1, 1999; 5(5): 1093 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ando, T. Kubin, W. Schaper, and J. Schaper Cardiac microvascular endothelial cells express alpha -smooth muscle actin and show low NOS III activity Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1755 - H1768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bouloumie, V. B. Schini-Kerth, and R. Busse Vascular endothelial growth factor up-regulates nitric oxide synthase expression in endothelial cells Cardiovasc Res, March 1, 1999; 41(3): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Karantzoulis-Fegaras, H. Antoniou, S.-L. M. Lai, G. Kulkarni, C. D'Abreo, G. K. T. Wong, T. L. Miller, Y. Chan, J. Atkins, Y. Wang, et al. Characterization of the Human Endothelial Nitric-oxide Synthase Promoter J. Biol. Chem., January 29, 1999; 274(5): 3076 - 3093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Poppa, J. K. Miyashiro, M. A. Corson, and B. C. Berk Endothelial NO Synthase Is Increased in Regenerating Endothelium After Denuding Injury of the Rat Aorta Arterioscler. Thromb. Vasc. Biol., August 1, 1998; 18(8): 1312 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Förstermann, J.-p. Boissel, and H. Kleinert Expressional control of the `constitutive' isoforms of nitric oxide synthase (NOS I and NOS III) FASEB J, July 1, 1998; 12(10): 773 - 790. [Abstract] [Full Text]
|
|
|
|
|
|
W.-Z. Ying and P. W. Sanders Dietary salt enhances glomerular endothelial nitric oxide synthase through TGF-beta 1 Am J Physiol Renal Physiol, July 1, 1998; 275(1): F18 - F24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Bayraktutan, Z.-K. Yang, and A. M Shah Selective dysregulation of nitric oxide synthase type 3 in cardiac myocytes but not coronary microvascular endothelial cells of spontaneously hypertensive rat Cardiovasc Res, June 1, 1998; 38(3): 719 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mutunga, P. M. Preston, and K. J. Sumption Nitric Oxide is Produced by Cowdria ruminantium-Infected Bovine Pulmonary Endothelial Cells In Vitro and Is Stimulated by Gamma Interferon Infect. Immun., May 1, 1998; 66(5): 2115 - 2121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. O Okoye, P. D Losty, M. J Fisher, I. Wilmott, and D. A Lloyd Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia Arch. Dis. Child. Fetal Neonatal Ed., May 1, 1998; 78(3): 204F - 208. [Abstract] [Full Text]
|
|
|
|
|
|
J. D. Hood, C. J. Meininger, M. Ziche, and H. J. Granger VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H1054 - H1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Andries, D. L. Brutsaert, and S. U. Sys Nonuniformity of Endothelial Constitutive Nitric Oxide Synthase Distribution in Cardiac Endothelium Circ. Res., February 9, 1998; 82(2): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kleinert, T. Wallerath, C. Euchenhofer, I. Ihrig-Biedert, H. Li, and U. Forstermann Estrogens Increase Transcription of the Human Endothelial NO Synthase Gene : Analysis of the Transcription Factors Involved Hypertension, February 1, 1998; 31(2): 582 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. FARACI and D. D. HEISTAD Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels Physiol Rev, January 1, 1998; 78(1): 53 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bouloumie, J. Bauersachs, W. Linz, B. A. Scholkens, G. Wiemer, I. Fleming, and R. Busse Endothelial Dysfunction Coincides With an Enhanced Nitric Oxide Synthase Expression and Superoxide Anion Production Hypertension, October 1, 1997; 30(4): 934 - 941. [Abstract] [Full Text]
|
|
|
|
|
|
A. N. MacRitchie, S. S. Jun, Z. Chen, Z. German, I. S. Yuhanna, T. S. Sherman, and P. W. Shaul Estrogen Upregulates Endothelial Nitric Oxide Synthase Gene Expression in Fetal Pulmonary Artery Endothelium Circ. Res., September 19, 1997; 81(3): 355 - 362. [Abstract] [Full Text]
|
|
|
|
|
|
N. Inoue, S. Ramasamy, T. Fukai, R. M. Nerem, and D. G. Harrison Shear Stress Modulates Expression of Cu/Zn Superoxide Dismutase in Human Aortic Endothelial Cells Circ. Res., July 1, 1996; 79(1): 32 - 37. [Abstract] [Full Text]
|
|
|
|
|
|
K. Cieslik, C. S. Abrams, and K. K. Wu Up-regulation of Endothelial Nitric-oxide Synthase Promoter by the Phosphatidylinositol 3-Kinase gamma /Janus Kinase 2/MEK-1-dependent Pathway J. Biol. Chem., January 5, 2001; 276(2): 1211 - 1219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. V. Pechkovsky, G. Zissel, T. Goldmann, M. Einhaus, C. Taube, H. Magnussen, M. Schlaak, and J. Muller-Quernheim Pattern of NOS2 and NOS3 mRNA expression in human A549 cells and primary cultured AEC II Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L684 - L692. [Abstract] [Full Text] [PDF]
|
|