Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:677-683
Published online before print December 11, 2003, doi: 10.1161/01.ATV.0000112024.13727.2c
Published online before print December 11, 2003, doi: 10.1161/01.ATV.0000112024.13727.2c
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Vascular Biology |
Distinct Subcellular Localizations of Nox1 and Nox4 in Vascular Smooth Muscle Cells
From the Division of Cardiology (L.L.H., R.E.C., K.K.G.), Department of Medicine and Department of Pathology (D.L.), Emory University, Atlanta, GA; and the Department of Veterinary Molecular Biology (M.T.Q.), Montana State University, Boseman, MT.
Correspondence to Dr Lula L. Hilenski, Emory University School of Medicine, Division of Cardiology, 1639 Pierce Dr, 319 WMRB, Atlanta, GA 30322. E-mail lhilens{at}emory.edu
Objective— Reactive oxygen species (ROS) that act as signaling molecules in vascular smooth muscle cells (VSMC) and contribute to growth, hypertrophy, and migration in atherogenesis are produced by multi-subunit NAD(P)H oxidases. Nox1 and Nox4, two homologues to the phagocytic NAD(P)H subunit gp91phox, both generate ROS in VSMC but differ in their response to growth factors. We hypothesize that the opposing functions of Nox1 and Nox4 are reflected in their differential subcellular locations.
Methods and Results— We used immunofluorescence to visualize the NAD(P)H subunits Nox1, Nox4, and p22phox in cultured rat and human VSMC. Optical sectioning using confocal microscopy showed that Nox1 is co-localized with caveolin in punctate patches on the surface and along the cellular margins, whereas Nox4 is co-localized with vinculin in focal adhesions. These immunocytochemical distributions are supported by membrane fractionation experiments. Interestingly, p22phox, a membrane subunit that interacts with the Nox proteins, is found in surface labeling and in focal adhesions in patterns similar to Nox1 and Nox4, respectively.
Conclusions— The differential roles of Nox1 and Nox4 in VSMC may be correlated with their differential compartmentalization in specific signaling domains in the membrane and focal adhesions.
Key Words: Nox1 • Nox4 • NAD(P)H oxidase • caveolae • focal adhesions
This article has been cited by other articles:
 |
|
 |
|
  J. R. Peterson, M. A. Burmeister, X. Tian, Y. Zhou, M. R. Guruju, J. A. Stupinski, R. V. Sharma, and R. L. Davisson Genetic Silencing of Nox2 and Nox4 Reveals Differential Roles of These NADPH Oxidase Homologues in the Vasopressor and Dipsogenic Effects of Brain Angiotensin II Hypertension, November 1, 2009; 54(5): 1106 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Park, Y.-S. Chun, K. S. Park, S. J. Kim, S.-O. Choi, H.-L. Kim, and J.-W. Park Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K+ channels Am J Physiol Cell Physiol, October 1, 2009; 297(4): C855 - C864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Diaz, G. Shani, I. Pass, D. Anderson, M. Quintavalle, and S. A. Courtneidge Tks5-Dependent, Nox-Mediated Generation of Reactive Oxygen Species Is Necessary for Invadopodia Formation Sci. Signal., September 15, 2009; 2(88): ra53 - ra53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gianni, B. Diaz, N. Taulet, B. Fowler, S. A. Courtneidge, and G. M. Bokoch Novel p47phox-Related Organizers Regulate Localized NADPH Oxidase 1 (Nox1) Activity Sci. Signal., September 15, 2009; 2(88): ra54 - ra54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Block, Y. Gorin, and H. E. Abboud Subcellular localization of Nox4 and regulation in diabetes PNAS, August 25, 2009; 106(34): 14385 - 14390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Senou, M. J. Costa, C. Massart, M. Thimmesch, C. Khalifa, S. Poncin, M. Boucquey, A.-C. Gerard, J.-N. Audinot, C. Dessy, et al. Role of caveolin-1 in thyroid phenotype, cell homeostasis, and hormone synthesis: in vivo study of caveolin-1 knockout mice Am J Physiol Endocrinol Metab, August 1, 2009; 297(2): E438 - E451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Miller Jr NADPH Oxidase 4: Walking the Walk With Poldip2 Circ. Res., July 31, 2009; 105(3): 209 - 210. [Full Text] [PDF]
|
|
|
|
|
|
A. N. Lyle, N. N. Deshpande, Y. Taniyama, B. Seidel-Rogol, L. Pounkova, P. Du, C. Papaharalambus, B. Lassegue, and K. K. Griendling Poldip2, a Novel Regulator of Nox4 and Cytoskeletal Integrity in Vascular Smooth Muscle Cells Circ. Res., July 31, 2009; 105(3): 249 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sadok, A. Pierres, L. Dahan, C. Prevot, M. Lehmann, and H. Kovacic NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of {alpha}2/{alpha}3 Integrins Mol. Cell. Biol., July 15, 2009; 29(14): 3915 - 3928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Muteliefu, A. Enomoto, P. Jiang, M. Takahashi, and T. Niwa Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells Nephrol. Dial. Transplant., July 1, 2009; 24(7): 2051 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Y. Lee, A. S. Martin, P. K. Mehta, A. E. Dikalova, A. M. Garrido, S. R. Datla, E. Lyons, K.-H. Krause, B. Banfi, J. D. Lambeth, et al. Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 480 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xiao, Z. Luo, A. E. Pepe, A. Margariti, L. Zeng, and Q. Xu Embryonic stem cell differentiation into smooth muscle cells is mediated by Nox4-produced H2O2 Am J Physiol Cell Physiol, April 1, 2009; 296(4): C711 - C723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Wolin Reactive oxygen species and the control of vascular function Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H539 - H549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhang, P. Harding, J. L. Garvin, R. Juncos, E. Peterson, L. A. Juncos, and R. Liu Isoforms and Functions of NAD(P)H Oxidase at the Macula Densa Hypertension, March 1, 2009; 53(3): 556 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. von Lohneysen, D. Noack, A. J. Jesaitis, M. C. Dinauer, and U. G. Knaus Mutational Analysis Reveals Distinct Features of the Nox4-p22phox Complex J. Biol. Chem., December 12, 2008; 283(50): 35273 - 35282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chen, M. T. Kirber, H. Xiao, Y. Yang, and J. F. Keaney Jr. Regulation of ROS signal transduction by NADPH oxidase 4 localization J. Cell Biol., October 22, 2008; 181(7): 1129 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kawahara and J. D. Lambeth Phosphatidylinositol (4,5)-bisphosphate Modulates Nox5 Localization via an N-Terminal Polybasic Region Mol. Biol. Cell, October 1, 2008; 19(10): 4020 - 4031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kinoshita, N. Matsuda, H. Kaba, N. Hatakeyama, T. Azma, K. Nakahata, Y. Kuroda, K. Tange, H. Iranami, and Y. Hatano Roles of Phosphatidylinositol 3-Kinase-Akt and NADPH Oxidase in Adenosine 5'-Triphosphate-Sensitive K+ Channel Function Impaired by High Glucose in the Human Artery Hypertension, September 1, 2008; 52(3): 507 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Anilkumar, R. Weber, M. Zhang, A. Brewer, and A. M. Shah Nox4 and Nox2 NADPH Oxidases Mediate Distinct Cellular Redox Signaling Responses to Agonist Stimulation Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1347 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Haurani, M. E. Cifuentes, A. D. Shepard, and P. J. Pagano Nox4 Oxidase Overexpression Specifically Decreases Endogenous Nox4 mRNA and Inhibits Angiotensin II-Induced Adventitial Myofibroblast Migration Hypertension, July 1, 2008; 52(1): 143 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jacobson, C. Yan, Q. Gao, T. Rincon-Skinner, A. Rivera, J. Edwards, A. Huang, G. Kaley, and D. Sun Aging enhances pressure-induced arterial superoxide formation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1344 - H1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Williams and D. G. Allen The role of reactive oxygen species in the hearts of dystrophin-deficient mdx mice Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1969 - H1977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Orient, A. Donko, A. Szabo, T. L. Leto, and M. Geiszt Novel sources of reactive oxygen species in the human body Nephrol. Dial. Transplant., May 1, 2007; 22(5): 1281 - 1288. [Full Text] [PDF]
|
|
|
|
|
|
J. K. Bendall, R. Rinze, D. Adlam, A. L. Tatham, J. de Bono, and K. M. Channon Endothelial Nox2 Overexpression Potentiates Vascular Oxidative Stress and Hemodynamic Response to Angiotensin II: Studies in Endothelial-Targeted Nox2 Transgenic Mice Circ. Res., April 13, 2007; 100(7): 1016 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Deliri and C. A. McNamara Nox 4 Regulation of Vascular Smooth Muscle Cell Differentiation Marker Gene Expression Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 12 - 14. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Clempus, D. Sorescu, A. E. Dikalova, L. Pounkova, P. Jo, G. P. Sorescu, B. Lassegue, and K. K. Griendling Nox4 Is Required for Maintenance of the Differentiated Vascular Smooth Muscle Cell Phenotype Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 42 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhang, F. Zhang, R. Muh, F. Yi, K. Chalupsky, H. Cai, and P.-L. Li Autocrine/paracrine pattern of superoxide production through NAD(P)H oxidase in coronary arterial myocytes Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H483 - H495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ushio-Fukai and R. W. Alexander Caveolin-Dependent Angiotensin II Type 1 Receptor Signaling in Vascular Smooth Muscle Hypertension, November 1, 2006; 48(5): 797 - 803. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Zimmet and J. M. Hare Nitroso-Redox Interactions in the Cardiovascular System Circulation, October 3, 2006; 114(14): 1531 - 1544. [Full Text] [PDF]
|
|
|
|
|
|
L. S. Terada Specificity in reactive oxidant signaling: think globally, act locally J. Cell Biol., August 28, 2006; 174(5): 615 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ushio-Fukai Localizing NADPH Oxidase-Derived ROS Sci. Signal., August 22, 2006; 2006(349): re8 - re8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Lyle and K. K. Griendling Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology, August 1, 2006; 21: 269 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Shah and H. Sauer Transmitting biological information using oxygen: Reactive oxygen species as signalling molecules in cardiovascular pathophysiology Cardiovasc Res, July 15, 2006; 71(2): 191 - 194. [Full Text] [PDF]
|
|
|
|
|
|
R. E. Clempus and K. K. Griendling Reactive oxygen species signaling in vascular smooth muscle cells Cardiovasc Res, July 15, 2006; 71(2): 216 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Paravicini and R. M. Touyz Redox signaling in hypertension Cardiovasc Res, July 15, 2006; 71(2): 247 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Geiszt NADPH oxidases: New kids on the block Cardiovasc Res, July 15, 2006; 71(2): 289 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hunyady and K. J. Catt Pleiotropic AT1 Receptor Signaling Pathways Mediating Physiological and Pathogenic Actions of Angiotensin II Mol. Endocrinol., May 1, 2006; 20(5): 953 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Hordijk Regulation of NADPH Oxidases: The Role of Rac Proteins Circ. Res., March 3, 2006; 98(4): 453 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ardanaz and P. J. Pagano Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Experimental Biology and Medicine, March 1, 2006; 231(3): 237 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kuroda, K. Nakagawa, T. Yamasaki, K.-i. Nakamura, R. Takeya, F. Kuribayashi, S. Imajoh-Ohmi, K. Igarashi, Y. Shibata, K. Sueishi, et al. The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells Genes Cells, December 1, 2005; 10(12): 1139 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Sheppard, M. R. Kelher, E. E. Moore, N. J. D. McLaughlin, A. Banerjee, and C. C. Silliman Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation J. Leukoc. Biol., November 1, 2005; 78(5): 1025 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dikalova, R. Clempus, B. Lassegue, G. Cheng, J. McCoy, S. Dikalov, A. S. Martin, A. Lyle, D. S. Weber, D. Weiss, et al. Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice Circulation, October 25, 2005; 112(17): 2668 - 2676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cai Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences Cardiovasc Res, October 1, 2005; 68(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zuo, M. Ushio-Fukai, S. Ikeda, L. Hilenski, N. Patrushev, and R. W. Alexander Caveolin-1 Is Essential for Activation of Rac1 and NAD(P)H Oxidase After Angiotensin II Type 1 Receptor Stimulation in Vascular Smooth Muscle Cells: Role in Redox Signaling and Vascular Hypertrophy Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1824 - 1830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Dudley Jr, N. E. Hoch, L. A. McCann, C. Honeycutt, L. Diamandopoulos, T. Fukai, D. G. Harrison, S. I. Dikalov, and J. Langberg Atrial Fibrillation Increases Production of Superoxide by the Left Atrium and Left Atrial Appendage: Role of the NADPH and Xanthine Oxidases Circulation, August 30, 2005; 112(9): 1266 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Wolin, M. Ahmad, and S. A. Gupte Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L159 - L173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zalba, O. Beloqui, G. S. Jose, M. U. Moreno, A. Fortuno, and J. Diez NADPH Oxidase-Dependent Superoxide Production Is Associated With Carotid Intima-Media Thickness in Subjects Free of Clinical Atherosclerotic Disease Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1452 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M Touyz Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II Exp Physiol, July 1, 2005; 90(4): 449 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ago, T. Kitazono, J. Kuroda, Y. Kumai, M. Kamouchi, H. Ooboshi, M. Wakisaka, T. Kawahara, K. Rokutan, S. Ibayashi, et al. NAD(P)H Oxidases in Rat Basilar Arterial Endothelial Cells Stroke, May 1, 2005; 36(5): 1040 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cai NAD(P)H Oxidase-Dependent Self-Propagation of Hydrogen Peroxide and Vascular Disease Circ. Res., April 29, 2005; 96(8): 818 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Djordjevic, R. S. BelAiba, S. Bonello, J. Pfeilschifter, J. Hess, and A. Gorlach Human Urotensin II Is a Novel Activator of NADPH Oxidase in Human Pulmonary Artery Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 519 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Goldstein, K. Mahadev, and X. Wu Redox Paradox: Insulin Action Is Facilitated by Insulin-Stimulated Reactive Oxygen Species With Multiple Potential Signaling Targets Diabetes, February 1, 2005; 54(2): 311 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F.H. Mueller, K. Laude, J. S. McNally, and D. G. Harrison Redox Mechanisms in Blood Vessels Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 274 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Wilcox and D. Gutterman Focus on oxidative stress in the cardiovascular and renal systems Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H3 - H6. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Gupte, P. M. Kaminski, B. Floyd, R. Agarwal, N. Ali, M. Ahmad, J. Edwards, and M. S. Wolin Cytosolic NADPH may regulate differences in basal Nox oxidase-derived superoxide generation in bovine coronary and pulmonary arteries Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H13 - H21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Pedruzzi, C. Guichard, V. Ollivier, F. Driss, M. Fay, C. Prunet, J.-C. Marie, C. Pouzet, M. Samadi, C. Elbim, et al. NAD(P)H Oxidase Nox-4 Mediates 7-Ketocholesterol-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Aortic Smooth Muscle Cells Mol. Cell. Biol., December 15, 2004; 24(24): 10703 - 10717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Quinn and K. A. Gauss Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases J. Leukoc. Biol., October 1, 2004; 76(4): 760 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yokoyama and N. Inoue How Vascular NAD(P)H Oxidase Activity and Nox Isoform Expression are Regulated Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1540 - 1541. [Full Text] [PDF]
|
|
|
|
|
|
L. Zuo, M. Ushio-Fukai, L. L. Hilenski, and R. W. Alexander Microtubules Regulate Angiotensin II Type 1 Receptor and Rac1 Localization in Caveolae/Lipid Rafts: Role in Redox Signaling Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1223 - 1228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Wolin Subcellular Localization of Nox-Containing Oxidases Provides Unique Insight Into Their Role in Vascular Oxidant Signaling Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 625 - 627. [Full Text] [PDF]
|
|