The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation
Open accessAbstract
NOX4 is an enigmatic member of the NOX (NADPH oxidase) family of ROS (reactive oxygen species)-generating NADPH oxidases. NOX4 has a wide tissue distribution, but the physiological function and activation mechanisms are largely unknown, and its pharmacology is poorly understood. We have generated cell lines expressing NOX4 upon tetracycline induction. Tetracycline induced a rapid increase in NOX4 mRNA (1 h) followed closely (2 h) by a release of ROS. Upon tetracycline withdrawal, NOX4 mRNA levels and ROS release decreased rapidly (<24 h). In membrane preparations, NOX4 activity was selective for NADPH over NADH and did not require the addition of cytosol. The pharmacological profile of NOX4 was distinct from other NOX isoforms: DPI (diphenyleneiodonium chloride) and thioridazine inhibited the enzyme efficiently, whereas apocynin and gliotoxin did not (IC(50)>100 muM). The pattern of NOX4-dependent ROS generation was unique: (i) ROS release upon NOX4 induction was spontaneous without need for a stimulus, and (ii) the type of ROS released from NOX4-expressing cells was H(2)O(2), whereas superoxide (O(2)(-)) was almost undetectable. Probes that allow detection of intracellular O(2)(-) generation yielded differential results: DHE (dihydroethidium) fluorescence and ACP (1-acetoxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine) ESR measurements did not detect any NOX4 signal, whereas a robust signal was observed with NBT. Thus NOX4 probably generates O(2)(-) within an intracellular compartment that is accessible to NBT (Nitro Blue Tetrazolium), but not to DHE or ACP. In conclusion, NOX4 has a distinct pharmacology and pattern of ROS generation. The close correlation between NOX4 mRNA and ROS generation might hint towards a function as an inducible NOX isoform.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“NOX4 produces ROS constitutively [37].”
In the citing paper
“Since NOX4 is a constitutively active form among the NOX isoforms, the activity of NOX4 depends on its expression [37].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Self-citationNOX enzymes and the biology of reactive oxygen
Lambeth, J. D. (2004) · Nature Reviews Immunology · doi:10.1038/nri1312 · Cited by 3,125
Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.
Griendling, K. K., Minieri, C. A., Ollerenshaw, J. D., & Alexander, R. W. (1994) · Circulation Research · doi:10.1161/01.res.74.6.1141 · Cited by 2,735
Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction
Berridge, M. V., Herst, P. M., & Tan, A. S. (2005) · Biotechnology Annual Review · doi:10.1016/s1387-2656(05)11004-7 · Cited by 2,222
Chen, C. A., & Okayama, H. (1990) · PubMed · Cited by 898
Identification of Renox, an NAD(P)H oxidase in kidney
Geiszt, M., Kopp, J. B., Várnai, P., & Leto, T. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130135897 · Cited by 840
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
Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases
Martyn, K. D., Frederick, L. M., von Loehneysen, K., Dinauer, M. C., & Knaus, U. G. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2005.03.023 · Cited by 783
Stolk, J. N., Hiltermann, T. J. N., Dijkman, J. H., & Verhoeven, A. J. (1994) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.11.1.8018341 · Cited by 650
A Ca2+-activated NADPH Oxidase in Testis, Spleen, and Lymph Nodes
Bánfi, B., Molnár, G., Maturana, A., Steger, K., Hegedûs, B., Demaurex, N., & Krause, K.-H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103034200 · Cited by 622
Self-citationAmbasta, R. K., Kumar, P., Griendling, K. K., Schmidt, H. H. H. W., Busse, R., & Brandes, R. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406486200 · Cited by 541
Mahadev, K., Motoshima, H., Wu, X., Ruddy, J. M., Arnold, R. S., Cheng, G., Lambeth, J. D., & Goldstein, B. J. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.5.1844-1854.2004 · Cited by 520
A Novel Superoxide-producing NAD(P)H Oxidase in Kidney
Shiose, A., Kuroda, J., Tsuruya, K., Hirai, M., Hirakata, H., Naito, S., Hattori, M., Sakaki, Y., & Sumimoto, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007597200 · Cited by 517
Nox4 as the Major Catalytic Component of an Endothelial NAD(P)H Oxidase
Ago, T., Kitazono, T., Ooboshi, H., Iyama, T., Han, Y. H., Takada, J., Wakisaka, M., Ibayashi, S., Utsumi, H., & Iida, M. (2004) · Circulation · doi:10.1161/01.cir.0000105680.92873.70 · Cited by 497
Nox4 NAD(P)H Oxidase Mediates Hypertrophy and Fibronectin Expression in the Diabetic Kidney
Gorin, Y. C., Block, K. L., Hernandez, J., Bhandari, B., Wagner, B., Barnes, J. L., & Abboud, H. E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502412200 · Cited by 496
Li, Y., & Trush, M. A. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9729 · Cited by 470
Pédruzzi, E., Guichard, C., Ollivier, V., Driss, F., Fay, M., Prunet, C., Marie, J., Pouzet, C., Samadi, M. H., Elbim, C., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10703-10717.2004 · Cited by 441
Sturrock, A., Cahill, B., Norman, K., Huecksteadt, T. P., Hill, K., Sanders, K., Karwande, S. V., Stringham, J. C., Bull, D. A., Gleich, M., et al. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00269.2005 · Cited by 402
Mechanism of Ca2+ Activation of the NADPH Oxidase 5 (NOX5)
Bánfi, B., Tirone, F., Durussel, I., Knisz, J., Moskwa, P., Molnár, G. Z., Krause, K.-H., & Cox, J. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310268200 · Cited by 389
Self-citationNox4 Is Required for Maintenance of the Differentiated Vascular Smooth Muscle Cell Phenotype
Clempus, R. E., Sorescu, D., Dikalova, A., Pounkova, L., Jo, P. C., Sorescu, G. P., Lassegue, B. P., & Griendling, K. K. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000251500.94478.18 · Cited by 338
Expression and Localization of NOX2 and NOX4 in Primary Human Endothelial Cells
van Buul, J. D., Fernandez‐Borja, M., Anthony, E. C., & Hordijk, P. L. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.308 · Cited by 326
Li, J., Stouffs, M., Serrander, L., Bánfi, B., Bettiol, E., Charnay, Y., Steger, K., Krause, K., & Jaconi, M. E. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-06-0532 · Cited by 302
Self-citationNox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells
Gorin, Y. C., Ricono, J. M., Kim, N.-H., Bhandari, B., Choudhury, G. G., & Abboud, H. E. (2003) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00414.2002 · Cited by 277
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
Kawahara, T., Ritsick, D., Cheng, G., & Lambeth, J. D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501882200 · Cited by 231
A New Superoxide-generating Oxidase in Murine Osteoclasts
Yang, S., Madyastha, P. R., Bingel, S. A., Ries, W. L., & Key, L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m001004200 · Cited by 226
The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle
ELLMARK, S., DUSTING, G., NGTANGFUI, M., GUZZOPERNELL, N., & DRUMMOND, G. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.10.026 · Cited by 213
Novel Mechanism of Activation of NADPH Oxidase 5
Jagnandan, D., Church, J. E., Banfi, B., Stuehr, D. J., Marrero, M. B., & Fulton, D. J. R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608966200 · Cited by 210
The inhibition by diphenyleneiodonium and its analogues of superoxide generation by macrophages
Hancock, J. T., & Jones, O. T. (1987) · Biochemical Journal · doi:10.1042/bj2420103 · Cited by 208
An NAD(P)H oxidase regulates growth and transcription in melanoma cells
Brar, S. S., Kennedy, T. P., Sturrock, A., Huecksteadt, T. P., Quinn, M. T., Whorton, A. R., & Hoidal, J. R. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00496.2001 · Cited by 183
van den Worm, E., Beukelman, C. J., van den Berg, A. J. J., Kroes, B. H., Labadie, R. P., & van Dijk, H. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)01516-3 · Cited by 172
Hu, T., RamachandraRao, S., Siva, S., Valancius, C., Zhu, Y., Mahadev, K., Toh, I., Goldstein, B. J., Woolkalís, M. J., & Sharma, K. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00024.2005 · Cited by 166
Ali, M. H., Pearlstein, D. P., Mathieu, C. E., & Schumacker, P. T. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00389.2003 · Cited by 156
de la Harpe, J., & Nathan, C. (1985) · Journal of Immunological Methods · doi:10.1016/0022-1759(85)90089-4 · Cited by 150
Fungal Metabolite Gliotoxin Inhibits Assembly of the Human Respiratory Burst NADPH Oxidase
Tsunawaki, S., Yoshida, L. S., Nishida, S., Kobayashi, T., & Shimoyama, T. (2004) · Infection and Immunity · doi:10.1128/iai.72.6.3373-3382.2004 · Cited by 140
Gliotoxin-mediated apoptosis of activated human hepatic stellate cells
Kweon, Y.-O., Paik, Y., Schnabl, B., Qian, T., Lemasters, J. J., & Brenner, D. A. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(03)00178-8 · Cited by 139
Evaluation of assays for the measurement of bovine neutrophil reactive oxygen species
Rinaldi, M., Moroni, P., Paape, M. J., & Bannerman, D. D. (2006) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2006.09.009 · Cited by 115
Maranchie, J. K., & Zhan, Y. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2105 · Cited by 115
NOX4 as an oxygen sensor to regulate TASK-1 activity
Lee, Y.-M., Kim, B., Chun, Y., So, I., Choi, H., Kim, M.-S., & Park, J. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.05.025 · Cited by 113
Expression of isoforms of NADPH oxidase components in rat pancreatic islets
Uchizono, Y., Takeya, R., Iwase, M., Sasaki, N., Oku, M., Imoto, H., Iida, M., & Sumimoto, H. (2006) · Life Sciences · doi:10.1016/j.lfs.2006.08.031 · Cited by 111
Rodrigues, T., dos Santos, A. C., Pigoso, A. A., Mingatto, F. E., Uyemura, S. A., & Curti, C. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704672 · Cited by 85
Takeshita, K., Fujii, K., Anzai, K., & Ozawa, T. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.02.016 · Cited by 68
Development of Neutrophil Granule Diversity
Borregaard, N. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb46237.x · Cited by 68
Hampton, M. B., & Winterbourn, C. C. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)00181-i · Cited by 67
Role of NAD(P)H oxidase in the regulation of cardiac L-type Ca channel function during acute hypoxia
Hool, L. C., DiMaria, C., Viola, H. M., & Arthur, P. G. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.04.025 · Cited by 64
Nishida, S., Yoshida, L. S., Shimoyama, T., Nunoi, H., Kobayashi, T., & Tsunawaki, S. (2004) · Infection and Immunity · doi:10.1128/iai.73.1.235-244.2005 · Cited by 48
Yokoyama, H., Itoh, O., Aoyama, M., Obara, H., Ohya, H., & Kamada, H. (2000) · Magnetic Resonance Imaging · doi:10.1016/s0730-725x(00)00183-1 · Cited by 41
Hadjimitova, V. A., Traykov, T. T., Mileva, M. M., & Ribarov, S. R. (2002) · Zeitschrift für Naturforschung C · doi:10.1515/znc-2002-11-1220 · Cited by 15
Effect of phenothiazines on activated macrophage-induced luminol-dependent chemiluminescence.
Traykov, T. T., Hadjimitova, V. A., Goliysky, P., & Ribarov, S. R. (1997) · PubMed · Cited by 15
Flagged first, then by citations
Cited by
Sorted by citations
Reactive Oxygen Species in Inflammation and Tissue Injury
Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5149 · Cited by 4,897
Yunna, C., Mengru, H., Lei, W., & Weidong, C. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173090 · Cited by 2,454
Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery
Paulsen, C. E., & Carroll, K. S. (2013) · Chemical Reviews · doi:10.1021/cr300163e · Cited by 1,313
Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases
Nandi, A., Yan, L.-J., Jana, C. K., & Das, N. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9613090 · Cited by 1,185
Simpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044
“Since NOX activation relies upon the assembly of multiple subunits, the primary activity regulation is likely dependent on protein kinetics, except for the constitutively active NOX4 which is regulated at the transcriptional level [56,67].”
Background
Metadata
- Authors
- Serrander, L., Cartier, L., Bedard, K., Banfi, B., Lardy, B., Plastre, O., Sienkiewicz, A., Fórró, L., Schlegel, W., & Krause, K.-H.
- Affiliations
- University of Geneva (CH)
- Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
- Hôpital Albert Michallon (FR)
- École Polytechnique Fédérale de Lausanne (CH)
- Institute of Physics of Complex Matter, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
- Corresponding author
- Serrander, Lena
- Schlegel, Werner
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2007-07-26
- Volume
- 406
- Issue
- 1
- Pages
- 105-114
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1948990
- OpenAlex
- W1998073026
- Cited by
- 627
- References
- 49
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 19 · 2023: 25 · 2022: 22 · 2021: 37 · 2020: 30 · 2019: 36 · 2018: 31 · 2017: 29 · 2016: 33 · 2015: 47 · 2014: 51 · 2013: 50 · 2012: 43
- FWCI
- 13.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NOX4, NADPH oxidase, reactive oxygen species, hydrogen peroxide, superoxide, mRNA expression, tetracycline-inducible expression, diphenyleneiodonium, thioridazine, apocynin, gliotoxin, nitroblue tetrazolium reduction
- MeSH terms
- NADPH Oxidase 4, Animals, Cell Line, Cell Membrane, Cytosol, Electron Spin Resonance Spectroscopy, Enzyme Induction, Enzyme Inhibitors, Ethidium, Humans, Hydrogen Peroxide, Mitochondria, NAD, NADP, Nitroblue Tetrazolium, RNA, Messenger, Superoxides, Tetracycline, Time Factors, Gene Expression Regulation, Enzymologic, Reactive Oxygen Species, NADPH Oxidases, Mice
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
