Molecular Medicine |
From the Institut für Kardiovaskuläre Physiologie (A.G., R.P.B., K.N., M.A., R.B.), and Institut für Anatomie II (F.D.), Klinikum der J.W. Goethe-Universität, Frankfurt/Main, Germany.
Correspondence to Agnes Görlach, MD, Institut für Kardiovaskuläre Physiologie, Klinikum der JWG Universität, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany. E-mail a.goerlach{at}em.uni-frankfurt.de
AbstractReactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the leukocyte enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox-/-, and endothelial NO synthase (eNOS)-/- mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS-/- mice, but was attenuated in segments from gp91phox-/- mice. Endothelium-dependent relaxation was greater in aortae from gp91phox-/- than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox-/- mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing leukocyte-type NADPH oxidase. This enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO. (Circ Res. 2000;87:26-32.)
Key Words: oxygen radicals endothelial function smooth muscle cells p22phox
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B. Lassegue and R. E. Clempus Vascular NAD(P)H oxidases: specific features, expression, and regulation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R277 - R297. [Abstract] [Full Text] [PDF] |
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S. S. Brar, Z. Corbin, T. P. Kennedy, R. Hemendinger, L. Thornton, B. Bommarius, R. S. Arnold, A. R. Whorton, A. B. Sturrock, T. P. Huecksteadt, et al. NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells Am J Physiol Cell Physiol, August 1, 2003; 285(2): C353 - C369. [Abstract] [Full Text] [PDF] |
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E. Courtois, M. Marques, A. Barrientos, S. Casado, and A. Lopez-Farre Lead-Induced Downregulation of Soluble Guanylate Cyclase in Isolated Rat Aortic Segments Mediated by Reactive Oxygen Species and Cyclooxygenase-2 J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1464 - 1470. [Abstract] [Full Text] [PDF] |
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Y. Gu, Y. C. Xu, R. F. Wu, F. E. Nwariaku, R. F. Souza, S. C. Flores, and L. S. Terada p47phox Participates in Activation of RelA in Endothelial Cells J. Biol. Chem., May 2, 2003; 278(19): 17210 - 17217. [Abstract] [Full Text] [PDF] |
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T. Abiko, A. Abiko, A. C. Clermont, B. Shoelson, N. Horio, J. Takahashi, A. P. Adamis, G. L. King, and S.-E. Bursell Characterization of Retinal Leukostasis and Hemodynamics in Insulin Resistance and Diabetes: Role of Oxidants and Protein Kinase-C Activation Diabetes, March 1, 2003; 52(3): 829 - 837. [Abstract] [Full Text] [PDF] |
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P A J Krijnen, C Meischl, C E Hack, C J L M Meijer, C A Visser, D Roos, and H W M Niessen Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction J. Clin. Pathol., March 1, 2003; 56(3): 194 - 199. [Abstract] [Full Text] [PDF] |
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I. N. Hines, J. M. Hoffman, H. Scheerens, B. J. Day, H. Harada, K. P. Pavlick, S. Bharwani, R. Wolf, B. Gao, S. Flores, et al. Regulation of postischemic liver injury following different durations of ischemia Am J Physiol Gastrointest Liver Physiol, March 1, 2003; 284(3): G536 - G545. [Abstract] [Full Text] [PDF] |
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H.-Y. Sohn, F. Krotz, S. Zahler, T. Gloe, M. Keller, K. Theisen, T. M Schiele, V. Klauss, and U. Pohl Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation Cardiovasc Res, March 1, 2003; 57(3): 804 - 815. [Abstract] [Full Text] [PDF] |
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F. Cosentino, M. Eto, P. De Paolis, B. van der Loo, M. Bachschmid, V. Ullrich, A. Kouroedov, C. Delli Gatti, H. Joch, M. Volpe, et al. High Glucose Causes Upregulation of Cyclooxygenase-2 and Alters Prostanoid Profile in Human Endothelial Cells: Role of Protein Kinase C and Reactive Oxygen Species Circulation, February 25, 2003; 107(7): 1017 - 1023. [Abstract] [Full Text] [PDF] |
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A Perner, L Andresen, G Pedersen, and J Rask-Madsen Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells Gut, February 1, 2003; 52(2): 231 - 236. [Abstract] [Full Text] [PDF] |
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D. X. Zhang, A.-P. Zou, and P.-L. Li Ceramide-induced activation of NADPH oxidase and endothelial dysfunction in small coronary arteries Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H605 - H612. [Abstract] [Full Text] [PDF] |
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M. Ushio-Fukai, Y. Tang, T. Fukai, S. I. Dikalov, Y. Ma, M. Fujimoto, M. T. Quinn, P. J. Pagano, C. Johnson, and R. W. Alexander Novel Role of gp91phox-Containing NAD(P)H Oxidase in Vascular Endothelial Growth Factor-Induced Signaling and Angiogenesis Circ. Res., December 13, 2002; 91(12): 1160 - 1167. [Abstract] [Full Text] [PDF] |
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J.-J. Cheng, Y.-J. Chao, and D. L. Wang Cyclic Strain Activates Redox-sensitive Proline-rich Tyrosine Kinase 2 (PYK2) in Endothelial Cells J. Biol. Chem., December 6, 2002; 277(50): 48152 - 48157. [Abstract] [Full Text] [PDF] |
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D. R. Bell, K. E. Gochenaur, and J. Hecht O2--mediated impairment of coronary arterial relaxation is prevented by overnight treatment with 1 nM beta -estradiol J Appl Physiol, December 1, 2002; 93(6): 1952 - 1958. [Abstract] [Full Text] [PDF] |
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F. E. Rey and P. J. Pagano The Reactive Adventitia: Fibroblast Oxidase in Vascular Function Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 1962 - 1971. [Abstract] [Full Text] [PDF] |
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F. E. Rey, X.-C. Li, O. A. Carretero, J. L. Garvin, and P. J. Pagano Perivascular Superoxide Anion Contributes to Impairment of Endothelium-Dependent Relaxation: Role of gp91phox Circulation, November 5, 2002; 106(19): 2497 - 2502. [Abstract] [Full Text] [PDF] |
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U. Rueckschloss, M. T. Quinn, J. Holtz, and H. Morawietz Dose-Dependent Regulation of NAD(P)H Oxidase Expression by Angiotensin II in Human Endothelial Cells: Protective Effect of Angiotensin II Type 1 Receptor Blockade in Patients With Coronary Artery Disease Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1845 - 1851. [Abstract] [Full Text] [PDF] |
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N. H.M. Lopes, S. S. Vasudevan, D. Gregg, B. Selvakumar, P. J. Pagano, H. Kovacic, and P. J. Goldschmidt-Clermont Rac-Dependent Monocyte Chemoattractant Protein-1 Production Is Induced by Nutrient Deprivation Circ. Res., November 1, 2002; 91(9): 798 - 805. [Abstract] [Full Text] [PDF] |
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J.-M. Li, N. P. Gall, D. J. Grieve, M. Chen, and A. M. Shah Activation of NADPH Oxidase During Progression of Cardiac Hypertrophy to Failure Hypertension, October 1, 2002; 40(4): 477 - 484. [Abstract] [Full Text] [PDF] |
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L Van Heerebeek, C Meischl, W Stooker, C J L M Meijer, H W M Niessen, and D Roos NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system? J. Clin. Pathol., August 1, 2002; 55(8): 561 - 568. [Abstract] [Full Text] [PDF] |
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Y. C. Xu, R. F. Wu, Y. Gu, Y.-S. Yang, M.-C. Yang, F. E. Nwariaku, and L. S. Terada Involvement of TRAF4 in Oxidative Activation of c-Jun N-terminal Kinase J. Biol. Chem., July 26, 2002; 277(31): 28051 - 28057. [Abstract] [Full Text] [PDF] |
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C. Vecchione and R. P. Brandes Withdrawal of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Elicits Oxidative Stress and Induces Endothelial Dysfunction in Mice Circ. Res., July 26, 2002; 91(2): 173 - 179. [Abstract] [Full Text] [PDF] |
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