The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

Altenhöfer, Sebastian; Kleikers, Pamela W. M.; Radermacher, Kim A.; Scheurer, Peter; Rob Hermans, J. J.; Schiffers, Paul; Ho, Heidi; Wingler, Kirstin; Schmidt, Harald H. H. W.

doi:10.1007/s00018-012-1010-9

Cited by 371Redox biology and oxidative stressNitric Oxide and Endothelin EffectsNeutrophil, Myeloperoxidase and Oxidative Mechanisms

The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

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Altenhöfer, Sebastian, Kleikers, Pamela W. M., Radermacher, Kim A., Scheurer, Peter, Rob Hermans, J. J., Schiffers, Paul, Ho, Heidi, Wingler, Kirstin +1 more·2012·Cellular and Molecular Life Sciences

DOI 10.1007/s00018-012-1010-9PMC PMC3383958

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Abstract

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis.

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VAS2870 appears to inhibit all isoforms, with proven inhibitory effects at least for NOX1, NOX2, NOX4, and NOX5 isoforms.
“VAS2870 appears to inhibit all isoforms, with proven inhibitory effects at least for NOX1, NOX2, NOX4, and NOX5 isoforms (21, 520).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [21]
VAS2870 and VAS3947 do not have a noticeable effect on XO- or eNOS-dependent ROS production, so they can be considered specific pan-NOX inhibitors.
“These inhibitors do not have a noticeable effect on XO- or eNOS-dependent ROS production, so they can be considered specific pan-NOX inhibitors.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [21]
VAS2870 is a well validated NADPH oxidase inhibitor as it shows no intrinsic antioxidant activity, does not inhibit other flavoproteins and inhibits NADPH oxidase-mediated ROS production in vitro and in vivo.
“VAS2870 is a well validated NADPH oxidase inhibitor [341] as it shows no intrinsic antioxidant activity, does not inhibit other flavoproteins and inhibits NADPH oxidase-mediated ROS production in vitro and in vivo.”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [341]
VAS2870 is definitely not Nox2-specific.
“However, although initial experiments suggested VAS2870 to be Nox2-specific, it is definitely not [341,393,403,404].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [341]

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Hwang, J., Kleinhenz, D. J., Lassegue, B. P., Griendling, K. K., Dikalov, S., & Hart, C. M. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00474.2004 · Cited by 268 · see citing works
Novel Nox inhibitor VAS2870 attenuates PDGF-dependent smooth muscle cell chemotaxis, but not proliferation☆
TENFREYHAUS, H., HUNTGEBURTH, M., WINGLER, K., SCHNITKER, J., BAUMER, A., VANTLER, M., BEKHITE, M., WARTENBERG, M., SAUER, H., & ROSENKRANZ, S. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.01.022 · Cited by 259 · see citing works
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Nox4 Acts as a Switch Between Differentiation and Proliferation in Preadipocytes
Schröder, K., Wandzioch, K., Helmcke, I., & Brandes, R. P. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.174219 · Cited by 258 · see citing works
Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells
Basuroy, S., Bhattacharya, S., Leffler, C. W., & Parfenova, H. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00381.2008 · Cited by 254 · see citing works
Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment
Etoh, T., Inoguchi, T., Kakimoto, M., Sonoda, N., Kobayashi, K., Kuroda, J., Sumimoto, H., & Nawata, H. (2003) · Diabetologia · doi:10.1007/s00125-003-1205-6 · Cited by 253 · see citing works
Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells
Mochizuki, T., Furuta, S., Mitsushita, J., Shang, W. H., Ito, M., Yokoo, Y., Yamaura, M., Ishizone, S., Nakayama, J., Konagai, A., et al. (2006) · Oncogene · doi:10.1038/sj.onc.1209406 · Cited by 253 · see citing works
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 · see citing works
Regulation of NAD(P)H Oxidase by Associated Protein Disulfide Isomerase in Vascular Smooth Muscle Cells
Janiszewski, M., Lopes, L. R., Carmo, A. O., Pedro, M. D. A., Brandes, R. P., Santos, C. X. C., & Laurindo, F. R. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509255200 · Cited by 243 · see citing works
First in Class, Potent, and Orally Bioavailable NADPH Oxidase Isoform 4 (Nox4) Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis
Laleu, B., Gaggini, F., Orchard, M., Fioraso-Cartier, L., Cagnon, L., Houngninou-Molango, S., Gradia, A., Duboux, G., Merlot, C., Heitz, F., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100773e · Cited by 243 · see citing works
The many roles of NOX2 NADPH oxidase-derived ROS in immunity
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Tks5-Dependent, Nox-Mediated Generation of Reactive Oxygen Species Is Necessary for Invadopodia Formation
Diaz, B., Shani, G., Pass, I., Anderson, D., Quintavalle, M., & Courtneidge, S. A. (2009) · Science Signaling · doi:10.1126/scisignal.2000368 · Cited by 242 · see citing works
Comparative pharmacology of chemically distinct nadph oxidase inhibitors
Wind, S., Beuerlein, K., Eucker, T., Müller, H., Scheurer, P., Armitage, M., Ho, H., Schmidt, H., & Wingler, K. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00920.x · Cited by 241 · see citing works
Self-citation
Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation
Lee, M. Y., Martín, A. S., Mehta, P. K., Dikalova, A., Garrido, A. M., Datla, S. R., Lyons, E., Krause, K., Bánfi, B., Lambeth, J. D., et al. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.181925 · Cited by 234 · see citing works
Point Mutations in the Proline-rich Region of p22 Are Dominant Inhibitors of Nox1- and Nox2-dependent Reactive Oxygen Generation
Kawahara, T., Ritsick, D., Cheng, G., & Lambeth, J. D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501882200 · Cited by 231 · see citing works
Randomized Trials of Vitamin E in the Treatment and Prevention of Cardiovascular Disease
Eidelman, R. S., Hollar, D., Hebert, P. R., Lamas, G. A., & Hennekens, C. H. (2004) · Archives of Internal Medicine · doi:10.1001/archinte.164.14.1552 · Cited by 231 · see citing works
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 · see citing works
Carotenoids and the risk of developing lung cancer: a systematic review
Gallicchio, L. M., Lindsley, K. B., Matanoski, G., Tao, X. G., Chen, L., Lam, T. K., Shiels, M. S., Hammond, E. R., Robinson, K. A., Caulfield, L. E., et al. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/88.2.372 · Cited by 220 · see citing works
NADPH oxidase activity and function are profoundly greater in cerebral versus systemic arteries
Miller, A. A., Drummond, G. R., Schmidt, H. H. H. W., & Sobey, C. G. (2005) · Circulation Research · doi:10.1161/01.res.0000189301.10217.87 · Cited by 211 · cited 9× · see citing works
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Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells
Park, H., CHUN, J., Jung, H., CHOI, C., & Bae, Y. H. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.09.012 · Cited by 203 · see citing works
Classical Inhibitors of NOX NAD(P)H Oxidases Are Not Specific
Aldieri, E., Riganti, C., Polimeni, M., Gazzano, E., Lussiana, C., Campia, I., & Ghigo, D. (2008) · Current Drug Metabolism · doi:10.2174/138920008786049285 · Cited by 201 · see citing works
NOX2 Complex–Derived ROS as Immune Regulators
Sareila, O., Kelkka, T., Pizzolla, A., Hultqvist, M. H., & Holmdahl, R. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3635 · Cited by 200 · see citing works
NADPH Oxidase Is Required for the Sensory Plasticity of the Carotid Body by Chronic Intermittent Hypoxia
Peng, Y., Nanduri, J., Yuan, G., Wang, N., Deneris, E. S., Pendyala, S., Natarajan, V., Kumar, G. K., & Prabhakar, N. R. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4768-08.2009 · Cited by 197 · see citing works
Nox4 and Nox2 NADPH Oxidases Mediate Distinct Cellular Redox Signaling Responses to Agonist Stimulation
Anilkumar, N. P., Weber, R., Zhang, M., Brewer, A. C., & Shah, A. M. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.164277 · Cited by 195 · see citing works
Inhibition of NADPH Oxidase Activation by 4-(2-Aminoethyl)-benzenesulfonyl Fluoride and Related Compounds
Diatchuk, V., Lotan, O., Koshkin, V., Wikstroem, P., & Pick, E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.20.13292 · Cited by 195 · see citing works
A Novel and Specific NADPH Oxidase-1 (Nox1) Small-Molecule Inhibitor Blocks the Formation of Functional Invadopodia in Human Colon Cancer Cells
Gianni, D., Taulet, N., Zhang, H., DerMardirossian, C., Kister, J., Martinez, L., Roush, W. R., Brown, S. J., Bokoch, G. M., & Rosen, H. (2010) · ACS Chemical Biology · doi:10.1021/cb100219n · Cited by 192 · see citing works
Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 5 (Nox5) Regulation by Angiotensin II and Endothelin-1 Is Mediated via Calcium/Calmodulin-Dependent, Rac-1-Independent Pathways in Human Endothelial Cells
Montezano, A. C., Burger, D., Paravicini, T. M., Chignalia, A. Z., Yusuf, H., Almasri, M., He, Y., Callera, G. E., He, G., Krause, K.-H., et al. (2010) · Circulation Research · doi:10.1161/circresaha.109.216036 · Cited by 188 · see citing works
NADPH Oxidase 4 Contributes to Transformation Phenotype of Melanoma Cells by Regulating G2-M Cell Cycle Progression
Yamaura, M., Mitsushita, J., Furuta, S., Kiniwa, Y., Ashida, A., Goto, Y., Shang, W. H., Kubodera, M., Kato, M., Takata, M., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3745 · Cited by 187 · see citing works
Embryonic stem cell differentiation into smooth muscle cells is mediated by Nox4-produced H2O2
Xiao, Q., Luo, Z., Pepe, A. E., Margariti, A., Zeng, L., & Xu, Q. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00442.2008 · Cited by 184 · see citing works
Hepatocyte NAD(P)H Oxidases as an Endogenous Source of Reactive Oxygen Species During Hepatitis C Virus Infection
de Mochel, N. S. R., Seronello, S., Wang, S. H., Ito, C., Zheng, J. X., Liang, J. T., Lambeth, D. J., & Choi, J. (2010) · Hepatology · doi:10.1002/hep.23671 · Cited by 183 · see citing works
Role of Nox4 and Nox2 in Hyperoxia-Induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells
Pendyala, S., Gorshkova, I. A., Usatyuk, P. V., He, D., Pennathur, A., Lambeth, J. D., Thannickal, V. J., & Natarajan, V. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2203 · Cited by 182 · see citing works
Oxidative Stress and Endothelial Dysfunction in Aortas of Aged Spontaneously Hypertensive Rats by NOX1/2 Is Reversed by NADPH Oxidase Inhibition
Wind, S., Beuerlein, K., Armitage, M. E., Taye, A., Kumar, A. H. S., Janowitz, D., Neff, C., Shah, A. M., Wingler, K., & Schmidt, H. H. H. W. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.149187 · Cited by 181 · see citing works
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Important Role of Nox4 Type NADPH Oxidase in Angiogenic Responses in Human Microvascular Endothelial Cells In Vitro
Datla, S. R., Peshavariya, H., Dusting, G. J., Mahadev, K., Goldstein, B. J., & Jiang, F. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.149450 · Cited by 177 · see citing works
Nox4 is a Novel Inducible Source of Reactive Oxygen Species in Monocytes and Macrophages and Mediates Oxidized Low Density Lipoprotein–Induced Macrophage Death
Lee, C. F., Qiao, M., Schröder, K., Zhao, Q. D., & Asmis, R. (2010) · Circulation Research · doi:10.1161/circresaha.109.215392 · Cited by 167 · see citing works
Human Urotensin II Is a Novel Activator of NADPH Oxidase in Human Pulmonary Artery Smooth Muscle Cells
Djordjevic, T., BelAiba, R. S., Bonello, S., Pfeilschifter, J. M., Hess, J., & Görlach, A. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000154279.98244.eb · Cited by 164 · see citing works
Early lipopolysaccharide-induced reactive oxygen species production evokes necrotic cell death in human umbilical vein endothelial cells
Simón, F., & Fernández, R. (2009) · Journal of Hypertension · doi:10.1097/hjh.0b013e328329e31c · Cited by 161 · see citing works
Constitutive NADPH-Dependent Electron Transferase Activity of the Nox4 Dehydrogenase Domain
Nisimoto, Y., Jackson, H. M., Ogawa, H., Kawahara, T., & Lambeth, J. D. (2010) · Biochemistry · doi:10.1021/bi9022285 · Cited by 161 · see citing works
Bcr-Abl-mediated redox regulation of the PI3K/AKT pathway
Naughton, R., Quiney, C., Turner, S. D., & Cotter, T. G. (2009) · Leukemia · doi:10.1038/leu.2009.49 · Cited by 157 · see citing works
Effect of Gender on NADPH-Oxidase Activity, Expression, and Function in the Cerebral Circulation
Miller, A. A., Drummond, G. R., Mast, A., Schmidt, H. H. H. W., & Sobey, C. G. (2007) · Stroke · doi:10.1161/strokeaha.106.477406 · Cited by 155 · see citing works
Self-citation
NADPH Oxidase Promotes Pancreatic Cancer Cell Survival via Inhibiting JAK2 Dephosphorylation by Tyrosine Phosphatases
Lee, J. K., Edderkaoui, M., Truong, P. A., Ohno, I., Jang, K., Berti, A., Pandol, S. J., & Gukovskaya, A. S. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.08.022 · Cited by 153 · see citing works
Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease
Shekelle, P., Morton, S. C., Jungvig, L., Udani, J. K., Spar, M. D., Tu, W., Suttorp, M. J., Coulter, I. D., Newberry, S. J., & Hardy, M. L. (2004) · Journal of General Internal Medicine · doi:10.1111/j.1525-1497.2004.30090.x · Cited by 151 · see citing works
Reactive oxygen species derived from Nox4 mediateBMP2gene transcription and osteoblast differentiation
Mandal, C. C., Ganapathy, S., Gorin, Y. C., Mahadev, K., Block, K. L., Abboud, H. E., Harris, S. E., Ghosh-Choudhury, G., & Ghosh‐Choudhury, N. (2010) · Biochemical Journal · doi:10.1042/bj20100357 · Cited by 146 · see citing works
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 · see citing works
Extracellular matrix stimulates reactive oxygen species production and increases pancreatic cancer cell survival through 5-lipoxygenase and NADPH oxidase
Edderkaoui, M., Hong, P., Vaquero, E. C., Lee, J. K., Fischer, L., Friess, H., Büchler, M. W., Lerch, M. M., Pandol, S. J., & Gukovskaya, A. S. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00197.2005 · Cited by 145 · see citing works
Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart
Spurney, C. F., Knoblach, S. M., Pistilli, E. E., Nagaraju, K., Martin, G. R., & Hoffman, E. P. (2008) · Neuromuscular Disorders · doi:10.1016/j.nmd.2008.03.008 · Cited by 144 · see citing works
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 · see citing works
Intracellular expression of reactive oxygen species-generating NADPH oxidase NOX4 in normal and cancer thyroid tissues
Weyemi, U., Caillou, B., Talbot, M., Hassani, R. A. E., Lacroix, L., Chevallier, O., Ghuzlan, A. A., Roos, D., Bidart, J., Virion, A., et al. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0175 · Cited by 142 · see citing works
Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells
Meng, D., Lv, D., & Fang, J. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn173 · Cited by 140 · see citing works
Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 1 in Oxidative Burst Response to Toll-Like Receptor 5 Signaling in Large Intestinal Epithelial Cells
Kawahara, T., Kuwano, Y., Teshima-Kondo, S., Takeya, R., Sumimoto, H., Kishi, K., Tsunawaki, S., Hirayama, T., & Rokutan, K. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.3051 · Cited by 138 · see citing works
Angiotensin II-Dependent Chronic Hypertension and Cardiac Hypertrophy Are Unaffected by gp91phox-Containing NADPH Oxidase
Touyz, R. M., Mercure, C., He, Y., Javeshghani, D., Yao, G., Callera, G. E., Yogi, Á., Lochard, N., & Reudelhuber, T. L. (2005) · Hypertension · doi:10.1161/01.hyp.0000158845.49943.5e · Cited by 134 · see citing works
Nox4 mediates TGF-β1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells
Sturrock, A., Huecksteadt, T. P., Norman, K. G., Sanders, K. A., Murphy, T. M., Chitano, P., Wilson, K. M., Hoidal, J. R., & Kennedy, T. P. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00430.2006 · Cited by 132 · see citing works
Nox4 NAD(P)H Oxidase Mediates Src-dependent Tyrosine Phosphorylation of PDK-1 in Response to Angiotensin II
Block, K. L., Eid, A. A., Griendling, K. K., Lee, D., Wittrant, Y., & Gorin, Y. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803964200 · Cited by 131 · see citing works
NOX4 Regulates ROS Levels Under Normoxic and Hypoxic Conditions, Triggers Proliferation, and Inhibits Apoptosis in Pulmonary Artery Adventitial Fibroblasts
Li, S., Tabar, S. S., Malec, V., Eul, B. G., Klepetko, W., Weißmann, N., Grimminger, F., Seeger, W., Rose, F., & Hänze, J. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2035 · Cited by 129 · see citing works
Novel Nox inhibitor of oxLDL-induced reactive oxygen species formation in human endothelial cells
Stielow, C., Catar, R. A., Müller, G. M., Wingler, K., Scheurer, P., Schmidt, H. H. H. W., & Morawietz, H. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.03.114 · Cited by 125 · see citing works
Self-citation
Structural Insights into Nox4 and Nox2: Motifs Involved in Function and Cellular Localization
von Löhneysen, K., Noack, D., Wood, M. R., Friedman, J. S., & Knaus, U. G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01393-09 · Cited by 124 · see citing works
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 · see citing works
NADPH oxidase (NOX) isoforms are inhibited by celastrol with a dual mode of action
Jaquet, V., Marcoux, J., Forest, É., Leidal, K. G., McCormick, S. J., Westermaier, Y., Perozzo, R., Plastre, O., Fioraso-Cartier, L., Diebold, B. A., et al. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01439.x · Cited by 120 · see citing works
NAD(P)H Oxidases Regulate HIF-2α Protein Expression
Block, K. L., Gorin, Y. C., Hoover, P., Williams, P., Chełmicki, T., Clark, R. A., Yoneda, T., & Abboud, H. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611569200 · Cited by 117 · see citing works
Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice
Bhandarkar, S. S., Jaconi, M. E., Fried, L. E., Bonner, M. Y., Lefkove, B., Govindarajan, B., Perry, B. N., Parhar, R., MacKelfresh, J. B., Sohn, A. M., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci33877 · Cited by 114 · see citing works
Nox1, 2, 4, 5: Counting out oxidative stress
Wingler, K., Hermans, J., Schiffers, P., Moens, A., Paul, M., & Schmidt, H. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01249.x · Cited by 113 · see citing works
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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 112 · see citing works
Nox4 Is Critical for Hypoxia-Inducible Factor 2-α Transcriptional Activity in von Hippel-Lindau–Deficient Renal Cell Carcinoma
Maranchie, J. K., & Zhan, Y. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2105 · Cited by 111 · see citing works
Novel p47 phox -Related Organizers Regulate Localized NADPH Oxidase 1 (Nox1) Activity
Gianni, D., Díaz, B., Taulet, N., Fowler, B. J., Courtneidge, S. A., & Bokoch, G. (2009) · Science Signaling · doi:10.1126/scisignal.2000370 · Cited by 109 · see citing works
Association of gp91phox homolog Nox1 with anchorage-independent growth and MAP kinase-activation of transformed human keratinocytes
Chamulitrat, W., Schmidt, R., Tomakidi, P., Stremmel, W., Chunglok, W., Kawahara, T., & Rokutan, K. (2003) · Oncogene · doi:10.1038/sj.onc.1206654 · Cited by 108 · see citing works
Mutational Analysis Reveals Distinct Features of the Nox4-p22 Complex
von Löhneysen, K., Noack, D., Jesaitis, A. J., Dinauer, M. C., & Knaus, U. G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804200200 · Cited by 106 · see citing works
Oxidative Modification of Nuclear Mitogen-activated Protein Kinase Phosphatase 1 Is Involved in Transforming Growth Factor β1-induced Expression of Plasminogen Activator Inhibitor 1 in Fibroblasts
Liu, R.-M., Choi, J., Wu, J.-H., Pravia, K. A. G., Lewis, K. M., Brand, J. D., de Mochel, N. S. R., Krzywanski, D. M., Lambeth, J. D., Hagood, J. S., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.111732 · Cited by 106 · see citing works
Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells
Goyal, P., Weißmann, N., Rose, F., Grimminger, F., Schäfers, H., Seeger, W., & Hänze, J. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.089 · Cited by 100 · see citing works
Enhanced expression of NADPH oxidase Nox4 in human gliomas and its roles in cell proliferation and survival
Shono, T., Yokoyama, N., Uesaka, T., Kuroda, J., Takeya, R., Yamasaki, T., Amano, T., Mizoguchi, M., Suzuki, S. O., Niiro, H., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23569 · Cited by 99 · see citing works
Diesel exhaust particles induce matrix metalloprotease-1 in human lung epithelial cells via a NADP(H) oxidase/NOX4 redox-dependent mechanism
Amara, N., Bachoual, R., Desmard, M., Gołda, S., Guichard, C., Lanone, S., Aubier, M., Ogier‐Denis, É., & Boczkowski, J. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00445.2006 · Cited by 98 · see citing works
Genetic Silencing of Nox2 and Nox4 Reveals Differential Roles of These NADPH Oxidase Homologues in the Vasopressor and Dipsogenic Effects of Brain Angiotensin II
Peterson, J. R., Burmeister, M. A., Tian, X., Zhou, Y., Guruju, M. R., Stupinski, J. A., Sharma, R. V., & Davisson, R. L. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.140087 · Cited by 98 · see citing works
Control of Hepatic Nuclear Superoxide Production by Glucose 6-Phosphate Dehydrogenase and NADPH Oxidase-4
Spencer, N. Y., Yan, Z., Boudreau, R. L., Zhang, Y., Luo, M., Li, Q., Tian, X., Shah, A. M., Davisson, R. L., Davidson, B. L., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.193821 · Cited by 97 · see citing works
NADPH oxidase 5 (NOX5) interacts with and is regulated by calmodulin
Tirone, F., & Cox, J. A. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.02.047 · Cited by 94 · see citing works
Role of the Multidrug Resistance Protein-1 in Hypertension and Vascular Dysfunction Caused by Angiotensin II
Widder, J. D., Guzik, T. J., Mueller, C. F. H., Clempus, R. E., Schmidt, H. H. H. W., Dikalov, S., Griendling, K. K., Jones, D. P., & Harrison, D. G. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000259298.11129.a2 · Cited by 94 · see citing works
Self-citation
The Hypoxia-Inducible Factor-2α Is Stabilized by Oxidative Stress Involving NOX4
Diebold, I., Flügel, D., Becht, S., BelAiba, R. S., Bonello, S., Hess, J., Kietzmann, T., & Görlach, A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.3014 · Cited by 92 · see citing works
NADPH oxidase 4 mediates TGF-β-induced smooth muscle α-actin via p38MAPK and serum response factor
Martín-Garrido, A., Brown, D., Lyle, A. N., Dikalova, A., Seidel-Rogol, B. L., Lassegue, B. P., Martín, A. S., & Griendling, K. K. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.11.007 · Cited by 90 · see citing works
Heat shock protein gp96 and NAD(P)H oxidase 4 play key roles in Toll-like receptor 4-activated apoptosis during renal ischemia/reperfusion injury
Ben Mkaddem, S., Pedruzzi, E., Werts, C., Coant, N., Bens, M., Cluzeaud, F., Goujon, J. M., Ogier-Denis, E., & Vandewalle, A. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2010.26 · Cited by 90 · see citing works
Apocynin-induced vasodilation involves Rho kinase inhibition but not NADPH oxidase inhibition
Schluter, T., Steinbach, A. C., Steffen, A., Rettig, R., & Grisk, O. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn185 · Cited by 90 · see citing works
Differential roles of PKCα and PKCɛ in controlling the gene expression of Nox4 in human endothelial cells
Xu, H., Goettsch, C., Xia, N., Horke, S., Morawietz, H., Förstermann, U., & Li, H. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.01.023 · Cited by 89 · see citing works
Hsp90 Regulates NADPH Oxidase Activity and Is Necessary for Superoxide but Not Hydrogen Peroxide Production
Chen, F., Pandey, D., Chadli, A., Catravas, J., Chen, T., & Fulton, D. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3669 · Cited by 88 · see citing works
H2O2 activates Nox4 through PLA2‐dependent arachidonic acid production in adult cardiac fibroblasts
Colston, J. T., de la Rosa, S. D., Strader, J. R., Anderson, M. A., & Freeman, G. L. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.03.057 · Cited by 88 · see citing works
Hemodynamics influences vascular peroxynitrite formation: Implication for low-density lipoprotein apo-B-100 nitration
Hsiai, T. K., Hwang, J., Barr, M. L., Correa, A., Hamilton, R., Alavi, M., Rouhanizadeh, M., Cadenas, E., & Hazen, S. L. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.11.017 · Cited by 87 · see citing works
NADPH Oxidase-derived ROS Contributes to Upregulation of TRPC6 Expression in Puromycin Aminonucleoside-induced Podocyte Injury
Wang, Z., Wei, X., Zhang, Y., Ma, X., Li, B., Zhang, S., Du, P., Zhang, X., & Yi, F. (2009) · Cellular Physiology and Biochemistry · doi:10.1159/000257517 · Cited by 84 · see citing works
The inhibition of the epidermal growth factor (EGF) pathway enhances TGF-β-induced apoptosis in rat hepatoma cells through inducing oxidative stress coincident with a change in the expression pattern of the NADPH oxidases (NOX) isoforms
Sancho, P., Bertrán, E., Caja, L., Carmona‐Cuenca, I., Murillo, M. M., & Fabregat, I. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.09.003 · Cited by 83 · see citing works
Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation
Mouche, S., Mkaddem, S. B., Wang, W., Katić, M., Tseng, Y., Carnésecchi, S., Steger, K., Foti, M., Meier, C. A., Muzzin, P., et al. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2007.03.003 · Cited by 81 · see citing works
Pro-Inflammatory Effects of Interleukin-17A on Vascular Smooth Muscle Cells Involve NAD(P)H- Oxidase Derived Reactive Oxygen Species
Pietrowski, E., Bender, B., Huppert, J., White, R., Luhmann, H. J., & Kuhlmann, C. R. W. (2010) · Journal of Vascular Research · doi:10.1159/000317400 · Cited by 79 · see citing works
NOX4 Expression in Human Microglia Leads to Constitutive Generation of Reactive Oxygen Species and to Constitutive IL-6 Expression
Li, B., Bedard, K., Sorce, S., Hinz, B., Dubois‐Dauphin, M., & Krause, K. (2009) · Journal of Innate Immunity · doi:10.1159/000235563 · Cited by 77 · see citing works
Interactions between the Cytosolic Components p47 and p67 of the Human Neutrophil NADPH Oxidase That Are Not Required for Activation in the Cell-free System
Leusen, J. H. W., Fluiter, K., Hilarius, P. M., Roos, D., Verhoeven, A. J., & Bolscher, B. G. J. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.19.11216 · Cited by 76 · see citing works
Off-target thiol alkylation by the NADPH oxidase inhibitor 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine (VAS2870)
Sun, Q.-A., Hess, D. T., Wang, B., Miyagi, M., & Stamler, J. S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.02.046 · Cited by 76 · see citing works
Nox4 overexpression activates reactive oxygen species and p38 MAPK in human endothelial cells
Goettsch, C., Göettsch, W., Müller, G. M., Seebach, J., Schnittler, H., & Morawietz, H. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.01.107 · Cited by 69 · see citing works
Expression of NADPH oxidases and enhanced H2O2-generating activity in human coronary artery endothelial cells upon induction with tumor necrosis factor-α
Yoshida, L. S., & Tsunawaki, S. (2008) · International Immunopharmacology · doi:10.1016/j.intimp.2008.05.004 · Cited by 68 · see citing works
Critical role of hydrogen peroxide signaling in the sequential activation of p38 MAPK and eNOS in laminar shear stress
Bretón-Romero, R., González de Orduña, C., Romero, N., Sánchez-Gómez, F. J., de Álvaro, C., Porras, A., Rodríguez-Pascual, F., Laranjinha, J., Radi, R., & Lamas, S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.12.026 · Cited by 66 · cited 1× · see citing works
“by hydrogen peroxide [77], and the effect was the same in endothelial cells from NOX4 KO mice (Santiago Lamas, personal communication).”
Background
New insight into the Nox4 subcellular localization in HEK293 cells: First monoclonal antibodies against Nox4
Zhang, L., Nguyen, M. V. C., Lardy, B., Jesaitis, A. J., Grichine, A., Rousset, F., Talbot, M., Paclet, M., Qian, G., & Morel, F. (2010) · Biochimie · doi:10.1016/j.biochi.2010.11.001 · Cited by 64 · see citing works
Green tea (Camellia sinensis) Attenuates Nephropathy by Downregulating Nox4 NADPH Oxidase in Diabetic Spontaneously Hypertensive Rats
Ribaldo, P. D. B., Souza, D. S., Biswas, S. K., Block, K. L., de Faria, J. M. L., & de Faria, J. B. L. (2008) · Journal of Nutrition · doi:10.3945/jn.108.095018 · Cited by 64 · see citing works
The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases
Yu, J., Weïwer, M., Linhardt, R. J., & Dordick, J. S. (2008) · Current Vascular Pharmacology · doi:10.2174/157016108784911984 · Cited by 62 · see citing works
Nitric oxide down‐regulates the expression of the catalytic NADPH oxidase subunit Nox1 in rat renal mesangial cells
Plešková, M., Beck, K., Behrens, M. H., Huwiler, A., Fichtlscherer, B., Wingerter, O., Brandes, R. P., Mülsch, A., & Pfeilschifter, J. M. (2005) · The FASEB Journal · doi:10.1096/fj.05-3791fje · Cited by 61 · see citing works
Stress‐induced activation of Nox contributes to cell survival signalling via production of hydrogen peroxide
Groeger, G., Mackey, A. M., Pettigrew, C. A., Bhatt, L., & Cotter, T. G. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06081.x · Cited by 61 · see citing works
The ‘A’s and ‘O’s of NADPH oxidase regulation: A commentary on “Subcellular localization and function of alternatively spliced Noxo1 isoforms”
Opitz, N., Drummond, G. R., Selemidis, S., Meurer, S., & Schmidt, H. H. H. W. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.11.003 · Cited by 60 · see citing works
Self-citation
Decision Analysis Supports the Paradigm That Indiscriminate Supplementation of Vitamin E Does More Harm than Good
Dotan, Y., Pinchuk, I., Lichtenberg, D. A., & Leshno, M. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.178699 · Cited by 60 · see citing works
Subcellular localization and function of alternatively spliced Noxo1 isoforms
Ueyama, T., Lekstrom, K. J., Tsujibe, S., Saito, N., & Leto, T. L. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.08.024 · Cited by 59 · see citing works
A role for NADPH oxidase 4 in the activation of vascular endothelial cells by oxidized phospholipids
Lee, S., Gharavi, N. M., Honda, H. M., Chang, I., Kim, B., Jen, N., Li, R., Zimman, A., & Berliner, J. A. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.04.013 · Cited by 58 · see citing works
Phosphorylation of Blood Vessel Vasodilator-Stimulated Phosphoprotein at Serine 239 as a Functional Biochemical Marker of Endothelial Nitric Oxide/Cyclic GMP Signaling
Ibarra‐Alvarado, C., Galle, J., Melichar, V. O., Mameghani, A. T., & Schmidt, H. H. H. W. (2002) · Molecular Pharmacology · doi:10.1124/mol.61.2.312 · Cited by 56 · see citing works
Self-citation
Nox4 mediates the expression of plasminogen activator inhibitor-1 via p38 MAPK pathway in cultured human endothelial cells
Jaulmes, A., Sansilvestri, P., Rolland-Valognes, G., Bernhardt, F., Gaertner, R., Lockhart, B. P., Cordi, A. A., Wierzbicki, M., Rupin, A., & Verbeuren, T. J. (2009) · Thrombosis Research · doi:10.1016/j.thromres.2009.05.018 · Cited by 55 · see citing works
Constitutive NADPH Oxidase 4 Activity Resides in the Composition of the B-loop and the Penultimate C Terminus
von Löhneysen, K., Noack, D., Hayes, P., Friedman, J. S., & Knaus, U. G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.332494 · Cited by 53 · see citing works
Reactive oxygen species are involved in regulating α1-adrenoceptor-activated vascular smooth muscle contraction
Tsai, M.-H., & Jiang, M. J. (2010) · Journal of Biomedical Science · doi:10.1186/1423-0127-17-67 · Cited by 51 · see citing works
Translation-Linked mRNA Destabilization Accompanying Serum-Induced Nox4 Expression in Human Endothelial Cells
Peshavariya, H., Jiang, F., Taylor, C. J., Selemidis, S., Chang, C. W. T., & Dusting, G. J. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2579 · Cited by 50 · see citing works
The NADPH oxidase inhibitor VAS2870 impairs cell growth and enhances TGF-β-induced apoptosis of liver tumor cells
Sancho, P., & Fabregat, I. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.01.007 · Cited by 48 · see citing works
NADPH oxidase 4 mediates reactive oxygen species induction of CD146 dimerization in VEGF signal transduction
Zhuang, J., Jiang, T.-X., Lü, D., Luo, Y., Zheng, C., Feng, J., Yang, D., Chen, C., & Yan, X. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.04.007 · Cited by 46 · see citing works
Addition of the Antioxidant Probucol to Angiotensin II Type I Receptor Antagonist Arrests Progressive Mesangioproliferative Glomerulonephritis in the Rat
Kondo, S., Shimizu, M., Urushihara, M., et al. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005050519 · Cited by 46 · see citing works
The NADPH Oxidase Subunit p22 Inhibits the Function of the Tumor Suppressor Protein Tuberin
Block, K. L., Gorin, Y. C., New, D. D., Eid, A. A., Chełmicki, T., Reed, A. B., Choudhury, G. G., Parekh, D. J., & Abboud, H. E. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090606 · Cited by 43 · see citing works
The NADPH oxidase inhibitor diphenyleneiodonium is also a potent inhibitor of cholinesterases and the internal Ca2+pump
Tazzeo, T., Worek, F., & Janssen, L. J. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00394.x · Cited by 42 · see citing works
Extracellular hydrogen peroxide contributes to oxidative glutamate toxicity
Ha, J. S., Lim, H. M., & Park, S. S. (2010) · Brain Research · doi:10.1016/j.brainres.2010.08.086 · Cited by 41 · see citing works
Long-Term Cyclic Strain Downregulates Endothelial Nox4
Goettsch, C., Göettsch, W., Arsov, A., Hofbauer, L. C., Bornstein, S. R., & Morawietz, H. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2561 · Cited by 41 · see citing works
Nox4-dependent H2O2 production contributes to chronic glutamate toxicity in primary cortical neurons
Ha, J. S., Lee, J. E., Lee, J.-R., Lee, C.-S., Maeng, J.-S., Bae, Y. S., Kwon, K., & Park, S. S. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.03.021 · Cited by 41 · see citing works
D1-Like Receptors Regulate NADPH Oxidase Activity and Subunit Expression in Lipid Raft Microdomains of Renal Proximal Tubule Cells
Li, H., Han, W., Villar, V. A. M., et al. (2009) · Hypertension · doi:10.1161/hypertensionaha.108.120642 · Cited by 41 · see citing works
Identification of the defective NADPH‐oxidase component in Chronic Granulomatous Disease: a study of 57 European families
Casimir, C. M., Chetty, M. C., Bohler, M., Garcia, R. C., Fischer, A., Griscelli, C., Johnson, B., & Segal, A. W. (1992) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1992.tb01481.x · Cited by 40 · see citing works
NOX2 is the primary source of angiotensin II-induced superoxide in the macula densa
Fu, Y., Zhang, R., Lu, D., Liu, H., Chandrashekar, K., Juncos, L. A., & Liu, R. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00762.2009 · Cited by 39 · see citing works
Local production of O2− by NAD(P)H oxidase in the sarcoplasmic reticulum of coronary arterial myocytes: cADPR-mediated Ca2+ regulation
Zhang, F., Jin, S., Yi, F., Xia, M., Dewey, W. L., & Li, P. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.11.013 · Cited by 39 · see citing works
Inhibition of human vascular nadph oxidase by apocynin derived oligophenols
Mora-Pale, M., Weïwer, M., Yu, J., Linhardt, R. J., & Dordick, J. S. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.05.061 · Cited by 36 · see citing works
The elevated blood pressure of humanGRK4γA142Vtransgenic mice is not associated with increased ROS production
Wang, Z., Armando, I., Asico, L. D., Escano, C. S., Wang, X., Lu, Q., Felder, R. A., Schnackenberg, C. G., Sibley, D. R., Eisner, G. M., et al. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00944.2006 · Cited by 36 · see citing works
Mitogenic Signaling via Platelet-Derived Growth Factor β in Metanephric Mesenchymal Cells
Wagner, B., Ricono, J. M., Gorin, Y. C., et al. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006111229 · Cited by 34 · see citing works
NADPH oxidases are responsible for the failure of nitric oxide to inhibit migration of smooth muscle cells exposed to high glucose
Tong, X., & Schröder, K. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.08.026 · Cited by 33 · see citing works
Novel transcripts of Nox1 are regulated by alternative promoters and expressed under phenotypic modulation of vascular smooth muscle cells
Arakawa, N., Katsuyama, M., Matsuno, K., Urao, N., Tabuchi, Y., Okigaki, M., Matsubara, H., & Yabe‐Nishimura, C. (2006) · Biochemical Journal · doi:10.1042/bj20060300 · Cited by 29 · see citing works
The Role of NOX2 and “Novel Oxidases” in Airway Chemoreceptor O2 Sensing
Cutz, E., Pan, J., & Yeger, H. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-90-481-2259-2_49 · Cited by 22 · see citing works
Expression of a homolog in Caco-2 cells giving O2−-reconstituting ability to cytochrome b558 together with recombinant
Yoshida, L. S., Nishida, S., Shimoyama, T., Kawahara, T., Rokutan, K., & Tsunawaki, S. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02059-4 · Cited by 9 · see citing works
Probe Report for NOX1 Inhibitors
Brown, S., Gianni, D., Bokoch, G., et al. (2010) · Europe PMC (PubMed Central) · Cited by 7 · see citing works
PPAR{gamma} regulates hypoxia-induced Nox4 expression in human pulmonary artery smooth muscle cells through NF-{kappa}B.
Lu, X., Murphy, T. C., Nanes, M. S., & Hart, C. M. (2010) · PubMed · doi:10.1152/ajplung.00090.2010 · Cited by 7 · see citing works
Abstract 2514: Role of NADPH oxidase 4 in Brain Endothelial Cells after Ischemic Stroke
Arimura, K., Ago, T., Kuroda, J., Ishitsuka, K., Nishimura, A., Sugimori, H., Kamouchi, M., Sasaki, T., & Kitazono, T. (2012) · Stroke · doi:10.1161/str.43.suppl_1.a2514 · Cited by 4 · see citing works
The phagocyte NADPH oxidase (NOX2) regulates adaptive immune response at the level of both T cells and APCs (138.7)
Williams, M. S., Shatynski, K. E., & Chen, H. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.184.supp.138.7 · Cited by 3 · see citing works

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[120]Sedeek M Callera GE Montezano A Gutsol A Heitz F Szyndralewiez C Critical role of NOX4-based NADPH oxidase in glucose-induced oxidative stress in the kidney—implications in type 2 diabetic nephropathy Am J Physiol Renal Physiol 2010 299 6 F1348 F1358 10.1152/ajprenal.00028.2010 20630933 · DOI · Paper page

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ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease
Simpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044 · see citing works
“Neuronal expression of NOX does not appear to be constitutive and the validation of detection methods used by stringent controls and transcriptomic corroboration is inadequate [63,66].”
Background
Functions of ROS in Macrophages and Antimicrobial Immunity
Herb, M., & Schramm, M. (2021) · Antioxidants · doi:10.3390/antiox10020313 · Cited by 633 · see citing works
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
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Rochette, L., Lorin, J., Zeller, M., Guilland, J.-C., Lorgis, L., Cottin, Y., & Vergely, C. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.07.004 · Cited by 456 · see citing works
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Genetic Targeting or Pharmacologic Inhibition of NADPH Oxidase Nox4 Provides Renoprotection in Long-Term Diabetic Nephropathy
Jha, J. C., Gray, S. P., Barit, D., Okabe, J., El-Osta, A., Namikoshi, T., Thallas-Bonke, V., Wingler, K., Szyndralewiez, C., Heitz, F., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013070810 · Cited by 352 · see citing works
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New Insights on <i>NOX</i> Enzymes in the Central Nervous System
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Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor
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Hepatocyte nicotinamide adenine dinucleotide phosphate reduced oxidase 4 regulates stress signaling, fibrosis, and insulin sensitivity during development of steatohepatitis in mice
Bettaieb, A., Jiang, J. X., Sasaki, Y., Chao, T.-I., Kiss, Z., Chen, X., Tian, J., Katsuyama, M., Yabe-Nishimura, C., Xi, Y., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.009 · Cited by 167 · see citing works
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Pharmacology and Clinical Drug Candidates in Redox Medicine
Dao, V. T.-V., Casas, A. I., Maghzal, G. J., Seredenina, T., Kaludercic, N., Robledinos-Anton, N., Di Lisa, F., Stocker, R., Ghezzi, P., Jaquet, V., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6430 · Cited by 88 · see citing works
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Bidirectional interactions between <scp>NOX</scp>2‐type <scp>NADPH</scp> oxidase and the F‐actin cytoskeleton in neuronal growth cones
Munnamalai, V., Weaver, C. J., Weisheit, C. E., Venkatraman, P., Agim, Z. S., Quinn, M. T., & Suter, D. M. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12734 · Cited by 70 · see citing works
Deletion of NADPH oxidase 4 reduces severity of traumatic brain injury
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Alternative Splicing of NOX4 in the Failing Human Heart
Varga, Z. V., Pipicz, M., Baán, J. A., Baranyai, T., Koncsos, G., Leszek, P., Kuśmierczyk, M., Sánchez-Cabo, F., García-Pavía, P., Brenner, G. J., et al. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00935 · Cited by 43 · see citing works
Targeting of <scp>NADPH</scp> oxidase in vitro and in vivo suppresses fibroblast activation and experimental skin fibrosis
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Novel Nox homologues in the vasculature: focusing on Nox4 and Nox5
Montezano, A. C. I., Burger, D. E., Ceravolo, G. S., Yusuf, H., Montero, M. J., & Touyz, R. M. (2010) · Clinical Science · doi:10.1042/cs20100384 · Cited by 106 · see citing works
JAK/STAT Signaling Pathway Regulates Nox1 and Nox4-Based NADPH Oxidase in Human Aortic Smooth Muscle Cells
AdrianManea, IrinaTanase, L., MonicaRaicu, et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology
The Nox Family of NADPH Oxidases: Friend or Foe of the Vascular System?
Takac, I., Schröder, K., & Brandes, R. P. (2011) · Current Hypertension Reports · doi:10.1007/s11906-011-0238-3 · Cited by 142 · see citing works
Oxidative Stress and Endothelial Dysfunction in Aortas of Aged Spontaneously Hypertensive Rats by NOX1/2 Is Reversed by NADPH Oxidase Inhibition
Wind, S., Beuerlein, K., Armitage, M. E., Taye, A., Kumar, A. H. S., Janowitz, D., Neff, C., Shah, A. M., Wingler, K., & Schmidt, H. H. H. W. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.149187 · Cited by 181 · see citing works
Self-citation
NADPH oxidase upregulates intermediate‐conductance Ca2+ ‐ activated K+ channels (KCa3.1) in coronary smooth muscle
Gole, H., & Bowles, D. K. (2011) · The FASEB Journal · doi:10.1096/fasebj.25.1_supplement.1026.16

Authors: 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.
Affiliations: Maastricht University (NL)
Vasopharm (Germany) (DE)
Corresponding author: Schmidt, Harald H. H. W.
ORCID: Schiffers, Paul
Schmidt, Harald H. H. W.
Venue: Cellular and Molecular Life Sciences
Publisher: Springer Science and Business Media LLC
Published: 2012-05-31
Volume: 69
Issue: 14
Pages: 2327-2343
ISSN: 1420-682X (ISSN-L)
1420-9071
DOI: 10.1007/s00018-012-1010-9
PMC: PMC3383958
OpenAlex: W2088298159
Cited by: 371
References: 193
Citations by year: 2026: 7 · 2025: 10 · 2024: 16 · 2023: 18 · 2022: 26 · 2021: 21 · 2020: 35 · 2019: 34 · 2018: 25 · 2017: 31 · 2016: 26 · 2015: 29 · 2014: 34 · 2013: 45 · 2012: 14
FWCI: 3.56
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
Locations: Cellular and Molecular Life Sciences (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion, cc-by)
Research Publications (Maastricht University) (submittedVersion, other-oa)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: NADPH oxidase, NOX4, reactive oxygen species, oxidative stress, reductive stress, VAS2870, NADPH oxidase inhibitors, knockout mice, siRNA, pharmacological inhibitors, therapeutic target, stroke, heart failure, fibrosis
MeSH terms: Animals, Enzyme Inhibitors, Humans, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Protein Isoforms, Models, Animal, RNA Interference, RNA, Small Interfering

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The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

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