The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Distinct Subcellular Localizations of Nox1 and Nox4 in Vascular Smooth Muscle Cells
Abstract
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 gp91 phox , 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 p22 phox 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, p22 phox , 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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“NOX1 is found in caveolae and signalosomes of vascular cells (423, 431, 652).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [431]
Citations
Cites
1 retracted
Ushio‐Fukai, M., Hilenski, L. L., Santanam, N., Becker, P. L., Ma, Y., Griendling, K. K., & Alexander, R. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105901200 · Cited by 204
Self-citationRetractedFree Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855
Giancotti, F. G., & Ruoslahti, E. (1999) · Science · doi:10.1126/science.285.5430.1028 · Cited by 3,869
NAD(P)H Oxidase: Role in Cardiovascular Biology and Disease
Griendling, K. K., Sorescu, D., & Ushio-Fukai, M. (2000) · Circulation Research · doi:10.1161/01.res.86.5.494 · Cited by 2,886
Self-citationCaveolin, a protein component of caveolae membrane coats
Rothberg, K. G., Heuser, J. E., Donzell, W. C., Ying, Y., Glenney, J. R., & Anderson, R. G. W. (1992) · Cell · doi:10.1016/0092-8674(92)90143-z · Cited by 2,259
BABIOR, B. M. (1999) · Blood · doi:10.1182/blood.v93.5.1464 · Cited by 2,147
FOCAL ADHESIONS, CONTRACTILITY, AND SIGNALING
Burridge, K., & Chrzanowska‐Wodnicka, M. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.463 · Cited by 1,957
Okamoto, T., Schlegel, A., Scherer, P. E., & Lisanti, M. P. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5419 · Cited by 1,496
Cell transformation by the superoxide-generating oxidase Mox1
Suh, Y.-A., Arnold, R. S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A. B., Griendling, K. K., & Lambeth, J. D. (1999) · Nature · doi:10.1038/43459 · Cited by 1,480
Self-citationKilling activity of neutrophils is mediated through activation of proteases by K+ flux
Reeves, E. P., Lu, H., Jacobs, H. L., Messina, C. G. M., Bolsover, S., Gabella, G., Potma, E. O., Warley, A., Roes, J., & Segal, A. W. (2002) · Nature · doi:10.1038/416291a · Cited by 1,153
Cited by
Sorted by citations
Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
NOX enzymes and the biology of reactive oxygen
Lambeth, J. D. (2004) · Nature Reviews Immunology · doi:10.1038/nri1312 · Cited by 3,125
Self-citationChemistry and biology of reactive oxygen species in signaling or stress responses
Dickinson, B. C., & Chang, C. J. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.607 · Cited by 1,821
NADPH oxidases: An overview from structure to innate immunity-associated pathologies
Panday, A., Sahoo, M. K., Osorio, D., & Batra, S. (2015) · Cellular & Molecular Immunology · doi:10.1038/cmi.2014.89 · Cited by 944
Cross talk between mitochondria and NADPH oxidases
Dikalov, S. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.06.033 · Cited by 783
Cucoranu, I., Clempus, R., Dikalova, A., Phelan, P. J., Ariyan, S., Dikalov, S., & Sorescu, D. (2005) · Circulation Research · doi:10.1161/01.res.0000187457.24338.3d · Cited by 786
Self-citationDiabetes and Kidney Disease: Role of Oxidative Stress
Jha, J. C., Banal, C., Chow, B. S. M., Cooper, M. E., & Jandeleit-Dahm, K. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6664 · Cited by 660
NADPH Oxidases: Functions and Pathologies in the Vasculature
Lassègue, B., & Griendling, K. K. (2010) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.181610 · Cited by 592
Self-citationSantos, C. X. C., Tanaka, L. Y., Wosniak, J., & Laurindo, F. R. M. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2625 · Cited by 572
Hunyady, L., & Catt, K. J. (2006) · Molecular Endocrinology · doi:10.1210/me.2004-0536 · Cited by 541
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Evolution of nadph oxidase inhibitors: Selectivity and mechanisms for target engagement
Altenhöfer, S., Radermacher, K. A., Kleikers, P. W. M., Wingler, K., & Schmidt, H. H. H. W. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5814 · Cited by 521
Ago, T., Kuroda, J., Pain, J., Fu, C., Li, H., & Sadoshima, J. (2010) · Circulation Research · doi:10.1161/circresaha.109.213116 · Cited by 506
Quinn, M. T., & Gauss, K. A. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0404216 · Cited by 480
Self-citationDikalova, A., Clempus, R., Lassègue, B., Cheng, G., McCoy, J., Dikalov, S., Martin, A. S., Lyle, A., Weber, D. S., Weiss, D., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.538934 · Cited by 438
Self-citationPoldip2, a Novel Regulator of Nox4 and Cytoskeletal Integrity in Vascular Smooth Muscle Cells
Lyle, A. N., Deshpande, N. N., Taniyama, Y., Seidel-Rogol, B., Pounkova, L., Du, P., Papaharalambus, C., Lassègue, B., & Griendling, K. K. (2009) · Circulation Research · doi:10.1161/circresaha.109.193722 · Cited by 428
Self-citationThe NOX toolbox: validating the role of NADPH oxidases in physiology and disease
Altenhöfer, S., Kleikers, P. W. M., Radermacher, K. A., Scheurer, P., Rob Hermans, J. J., Schiffers, P., Ho, H., Wingler, K., & Schmidt, H. H. H. W. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1010-9 · Cited by 371
Dikalov, S. I., & Nazarewicz, R. R. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4604 · Cited by 356
NAD(P)H Oxidase Mediates TGF-β1–Induced Activation of Kidney Myofibroblasts
Bondi, C. D., Manickam, N., Lee, D. Y., Block, K., Gorin, Y., Abboud, H. E., & Barnes, J. L. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009020146 · Cited by 297
Vallet, P., Charnay, Y., Steger, K., Ogier-Denis, E., Kovari, E., Herrmann, F., Michel, J.-P., & Szanto, I. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.12.038 · Cited by 291
Weyemi, U., Lagente-Chevallier, O., Boufraqech, M., Prenois, F., Courtin, F., Caillou, B., Talbot, M., Dardalhon, M., Al Ghuzlan, A., Bidart, J.-M., et al. (2012) · Oncogene · doi:10.1038/onc.2011.327 · Cited by 285
The superoxide‐producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells
Kuroda, J., Nakagawa, K., Yamasaki, T., Nakamura, K., Takeya, R., Kuribayashi, F., Imajoh‐Ohmi, S., Igarashi, K., Shibata, Y., Sueishi, K., et al. (2005) · Genes to Cells · doi:10.1111/j.1365-2443.2005.00907.x · Cited by 275
NOX2 and NOX4 Mediate Proliferative Response in Endothelial Cells
Petry, A., Djordjevic, T., Weitnauer, M., Kietzmann, T., Hess, J., & Görlach, A. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.1473 · Cited by 243
Diaz, B., Shani, G., Pass, I., Anderson, D., Quintavalle, M., & Courtneidge, S. A. (2009) · Science Signaling · doi:10.1126/scisignal.2000368 · Cited by 242
Rustenhoven, J., Aalderink, M., Scotter, E. L., Oldfield, R. L., Bergin, P. S., Mee, E. W., Graham, E. S., Faull, R. L. M., Curtis, M. A., Park, T. I.-H., et al. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0503-0 · Cited by 201
Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells
Jay, D. B., Papaharalambus, C. A., Seidel-Rogol, B., Dikalova, A. E., Lassègue, B., & Griendling, K. K. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.04.024 · Cited by 166
Self-citationROS-induced ROS release in vascular biology: redox-redox signaling
Zinkevich, N. S., & Gutterman, D. D. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01271.2010 · Cited by 163
Receptor Activation of NADPH Oxidases
Petry, A., Weitnauer, M., & Görlach, A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.3026 · Cited by 162
Bendall, J. K., Rinze, R., Adlam, D., Tatham, A. L., de Bono, J., & Channon, K. M. (2007) · Circulation Research · doi:10.1161/01.res.0000263381.83835.7b · Cited by 157
The nox4 inhibitor gkt137831 attenuates hypoxia-induced pulmonary vascular cell proliferation
Green, D. E., Murphy, T. C., Kang, B.-Y., Kleinhenz, J. M., Szyndralewiez, C., Page, P., Sutliff, R. L., & Hart, C. M. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0418oc · Cited by 146
Identification of Structural Elements in Nox1 and Nox4 Controlling Localization and Activity
Helmcke, I., Heumüller, S., Tikkanen, R., Schröder, K., & Brandes, R. P. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2383 · Cited by 145
Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism
Garrido-Urbani, S., Jemelin, S., Deffert, C., Carnesecchi, S., Basset, O., Szyndralewiez, C., Heitz, F., Page, P., Montet, X., Michalik, L., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014665 · Cited by 143
NADPH Oxidases and Mitochondria in Vascular Senescence
Salazar, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051327 · Cited by 133
Reactive oxygen species and the control of vascular function
Wolin, M. S. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01167.2008 · Cited by 133
Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2
Csányi, G., Cifuentes-Pagano, E., Al Ghouleh, I., Ranayhossaini, D. J., Egaña, L., Lopes, L. R., Jackson, H. M., Kelley, E. E., & Pagano, P. J. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.025 · Cited by 131
Differential effects of diabetes on the expression of the gp91phox homologues nox1 and nox4
Wendt, M. C., Daiber, A., Kleschyov, A. L., Mülsch, A., Sydow, K., Schulz, E., Chen, K., Keaney, J. F., Lassègue, B., Walter, U., et al. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.03.020 · Cited by 122
Self-citationNOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis
Santillo, M., Colantuoni, A., Mondola, P., Guida, B., & Damiano, S. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00194 · Cited by 95
The Plasma Membrane: A Platform for Intra- and Intercellular Redox Signaling
Nordzieke, D. E., & Medraño-Fernandez, I. (2018) · Antioxidants · doi:10.3390/antiox7110168 · Cited by 90
Yoshida, L. S., & Tsunawaki, S. (2008) · International Immunopharmacology · doi:10.1016/j.intimp.2008.05.004 · Cited by 68
Datla, S. R., McGrail, D. J., Vukelic, S., Huff, L. P., Lyle, A. N., Pounkova, L., Lee, M., Seidel-Rogol, B., Khalil, M. K., Hilenski, L. L., et al. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00918.2013 · Cited by 60
Self-citationFrazziano, G., Al Ghouleh, I., Baust, J., Shiva, S., Champion, H. C., & Pagano, P. J. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00977.2012 · Cited by 51
Zhang, G., Zhang, F., Muh, R., Yi, F., Chalupsky, K., Cai, H., & Li, P.-L. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00632.2006 · Cited by 42
The ambiguous aspects of oxygen
Napolitano, G., Fasciolo, G., & Venditti, P. (2022) · Oxygen · doi:10.3390/oxygen2030027 · Cited by 30
Zhang, Z.-Y., Qian, L.-L., & Wang, R.-X. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00698 · Cited by 12
Metadata
- Authors
- Hilenski, L. L., Clempus, R. E., Quinn, M. T., Lambeth, J. D., & Griendling, K. K.
- Affiliations
- Emory University (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2004-04
- Volume
- 24
- Issue
- 4
- Pages
- 677-683
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2115239727
- Cited by
- 573
- References
- 39
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 15 · 2022: 9 · 2021: 13 · 2020: 14 · 2019: 21 · 2018: 22 · 2017: 25 · 2016: 17 · 2015: 23 · 2014: 36 · 2013: 39 · 2012: 53
- FWCI
- 16.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 58000, HL38206, HL58863, P01HL058000, R01HL058863)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NOX1, NOX4, NADPH oxidase, reactive oxygen species, vascular smooth muscle cells, subcellular localization, p22phox, caveolin, focal adhesions, vinculin, membrane compartmentalization, atherogenesis
- MeSH terms
- NADPH Oxidase 1, NADPH Oxidase 4, Animals, Cell Division, Cell Fractionation, Cells, Cultured, Cytoskeleton, Humans, Male, Microscopy, Fluorescence, Muscle, Smooth, Vascular, NADH, NADPH Oxidoreductases, NADPH Dehydrogenase, Oxidation-Reduction, Phosphoproteins, Vinculin, Cellular Senescence, Rats, Sprague-Dawley, Reactive Oxygen Species, Microscopy, Confocal, NADPH Oxidases, Protein Subunits, Caveolae, Focal Adhesions, Caveolins, Membrane Transport Proteins, Myocytes, Smooth Muscle, Macromolecular Substances, Caveolin 1, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review