| 2001 |
NOX1 (then called nox1/mox-1) functions as a superoxide-generating NADPH oxidase in vascular smooth muscle cells. Antisense nox1 adenovirus completely inhibited the early phase of superoxide production induced by Ang II or PDGF and significantly decreased activation of p38 MAPK and Akt by Ang II, placing Nox1 upstream of these redox-sensitive signaling molecules. |
Antisense adenoviral knockdown of nox1 in VSMCs; superoxide measurement; Western blot for p38 MAPK and Akt activation |
Circulation Research |
High |
11348997
|
| 2001 |
H2O2 (not superoxide) is the primary mediator of Nox1-driven cell growth and transformation: co-expression of catalase in Nox1-expressing NIH 3T3 cells normalized H2O2 levels, reversed the transformed appearance, normalized growth rate, abolished tumorigenicity in athymic mice, and reversed the expression of >60% of Nox1-induced genes. |
Stable co-expression of catalase in Nox1-expressing NIH 3T3 cells; H2O2 and O2- measurement; tumor formation in athymic mice; gene expression profiling |
PNAS |
High |
11331784
|
| 2002 |
Nox1-derived H2O2 triggers the angiogenic switch: Nox1 markedly up-regulated VEGF mRNA and induced VEGFR1/VEGFR2 in vascular cells, and co-expression of catalase eliminated Nox1-induced VEGF induction, indicating H2O2 as the signal mediating angiogenesis. |
Nox1 overexpression in NIH 3T3 and DU-145 cells; tumor xenograft angiogenesis assay; VEGF mRNA quantification; catalase co-expression rescue |
PNAS |
Medium |
11805326
|
| 2005 |
Nox1 knockout mice (Nox1-/Y) show significantly blunted blood pressure elevation and reduced aortic superoxide production in response to Ang II infusion compared with wild-type, demonstrating that Nox1-derived ROS mediate the pressor response to Ang II by reducing nitric oxide bioavailability (endothelium-dependent relaxation and cGMP preserved in Nox1-/Y). |
Nox1 knockout mice; telemetric blood pressure monitoring; superoxide measurement; endothelium-dependent relaxation assays; cGMP measurement; L-NAME co-treatment |
Circulation |
High |
16246966
|
| 2006 |
Nox1 is directly activated by the small GTPase Rac1: constitutively active Rac1(G12V), but not wild-type Rac1 or CDC42, markedly stimulated Nox1-dependent ROS generation; Rac1 siRNA reduced Nox1-dependent ROS; Rac1(G12V) co-immunoprecipitated with Nox1, NOXO1, and NOXA1; NOXA1 TPR domain mutants that block Rac1 binding abolished Nox1 activity; and Rac1(G12V) formed a complex with Nox1 independently of NOXO1/NOXA1, indicating direct binding. |
Co-expression of Rac1/CDC42 mutants with Nox1/NOXO1/NOXA1 in HEK293 cells; ROS measurement; co-immunoprecipitation; siRNA knockdown; NOXA1 TPR domain mutagenesis |
Journal of Biological Chemistry |
High |
16636067
|
| 2007 |
PKA phosphorylates NoxA1 (the Nox1 activator) at Ser172 and Ser461, enhancing NoxA1 association with 14-3-3 proteins, causing dissociation of NoxA1 from the Nox1 complex at the plasma membrane, thereby inhibiting Nox1-dependent ROS production. Elevation of cAMP inhibited Nox1 activity, while PKA inhibition enhanced it, and 14-3-3ζ availability intensified this inhibitory effect. |
PKA phosphorylation site mapping; site-directed mutagenesis (Ser172A, Ser461A); co-immunoprecipitation; ROS measurement in HEK293 and colon cell lines; cAMP elevation; 14-3-3 binding assays |
Journal of Biological Chemistry |
High |
17913709
|
| 2007 |
TNF treatment induces formation of a signaling complex containing TRADD, RIP1, Nox1, and Rac1 in mouse fibroblasts undergoing necrosis. RIP1-deficient fibroblasts fail to form this complex, indicating RIP1 is essential for Nox1 recruitment. Dominant-negative TRADD or Rac1, or Nox1 siRNA knockdown, inhibited TNF-induced superoxide generation and necrotic cell death. |
Co-immunoprecipitation; dominant-negative TRADD/Rac1 expression; Nox1 siRNA; RIP1-deficient fibroblasts; cell death assays |
Molecular Cell |
High |
17560373
|
| 2008 |
Nox1 and Nox4 produce distinct reactive oxygen species: Nox1 depletion (antisense adenovirus) in rat aortic smooth muscle cells inhibited Ang II-stimulated superoxide production and H2O2 in membrane fractions and intact cells, whereas Nox4 depletion (siRNA) reduced basal H2O2 production but not Ang II-stimulated responses. This establishes that Nox1 generates predominantly superoxide that is subsequently converted to H2O2. |
Antisense Nox1 adenovirus; Nox4 siRNA; ESR spin-trapping; Amplex Red H2O2 assay; dihydroethidium; membrane fraction NADPH oxidase activity assay |
Free Radical Biology & Medicine |
High |
18760347
|
| 2009 |
The N-terminal domain of Nox1 determines its plasma membrane localization and the type of ROS released extracellularly (superoxide): TIRF microscopy showed Nox1 localizes to the plasma membrane while Nox4 colocalizes with ER markers. Chimeric Nox1/Nox4 proteins showed that the cytosolic tail of Nox4 fused to the transmembrane part of Nox1 rendered Nox1 constitutively active, and that inserting the Nox4 signal peptide into Nox1 shifted localization from plasma membrane to vesicle-like structures and switched extracellular ROS from superoxide to H2O2. |
TIRF microscopy; chimeric Nox1/Nox4 protein construction; ROS type measurement; N-terminal signal peptide swap mutagenesis; HEK293 expression system |
Antioxidants & Redox Signaling |
High |
19061439
|
| 2009 |
STAT1 and STAT3, activated via the JAK/STAT pathway, directly bind GAS elements in the NOX1 promoter and transcriptionally regulate Nox1 expression in human aortic smooth muscle cells. Chromatin immunoprecipitation confirmed physical interaction of STAT1/STAT3 with NOX1 promoter GAS elements; JAK/STAT inhibitors reduced IFNγ-induced Nox1 and Nox4 expression and NADPH oxidase activity. |
Chromatin immunoprecipitation (ChIP); promoter-reporter assays; STAT1/STAT3 overexpression; JAK/STAT inhibitors; real-time PCR; Western blot |
Arteriosclerosis, Thrombosis, and Vascular Biology |
High |
19834108
|
| 2010 |
TNF-α activates Nox1 via dynamin-dependent endocytosis to generate endosomal ROS, whereas thrombin activates Nox1 through EGFR transactivation without endosomal ROS generation. Both ligands required Nox1 and dynamin for PI3K-Akt-ATF-1 pathway activation, establishing spatially distinct mechanisms of Nox1 activation by different receptor-ligand complexes. |
Nox1 shRNA; dominant-negative dynamin; EGFR inhibitor AG1478; PI3K inhibitor; ROS compartment-specific measurements in smooth muscle cells |
Antioxidants & Redox Signaling |
Medium |
19737091
|
| 2010 |
Nox1-dependent superoxide production controls colon adenocarcinoma cell (HT29-D4) migration on collagen-I via regulation of α2β1 integrin membrane availability. Upstream, arachidonic acid metabolism through 12-lipoxygenase and protein kinase C delta activates Nox1, and 12-HETE (the 12-LOX product) restored Nox1-dependent superoxide and migration when 12-LOX was inhibited. |
Nox1 siRNA; 12-LOX inhibitors; PKC isoform inhibitors; superoxide measurement; integrin membrane availability assay; Boyden chamber migration |
Biochimica et Biophysica Acta |
Medium |
18023288
|
| 2010 |
Nox1 inhibits p53 transcriptional activity and proapoptotic function via a SIRT1-dependent mechanism: Nox1 inhibited p53 Lys382 acetylation (a SIRT1 target), impaired p53 proapoptotic transcriptional activity, and could not inhibit p53 when co-expressed with SIRT1 deacetylase-defective mutant (SIRT1HY), establishing a functional link between Nox1, SIRT1, and p53 acetylation. |
Nox1 overexpression and siRNA; SIRT1 siRNA and pharmacological inhibition (nicotinamide); SIRT1HY deacetylase-dead mutant co-expression; p53 acetylation (Lys382) assay; p53 reporter assay |
Free Radical Biology & Medicine |
Medium |
20171273
|
| 2010 |
A specific small-molecule inhibitor (ML171/2-acetylphenothiazine) selectively inhibits Nox1-dependent ROS generation at nanomolar concentrations with minimal activity on other Nox isoforms or other cellular ROS-producing enzymes. ML171 blocks ROS-dependent formation of invadopodia in colon cancer cells, and this effect is reversed by Nox1 overexpression, confirming selectivity. |
High-throughput screening; isoform-specific ROS assays; invadopodium formation assay; Nox1 overexpression rescue |
ACS Chemical Biology |
High |
20715845
|
| 2011 |
Nox1 mediates thrombin-induced EGFR transactivation, MMP-9 activation, N-cadherin shedding, and smooth muscle cell migration: Nox1 knockout SMCs failed to show thrombin-induced Src phosphorylation, EGFR transactivation, ERK1/2 and MMP-9 activation, or N-cadherin shedding, and SMC migration was rescued by Nox1 re-expression in KO cells. EGFR inhibitor AG1478 blocked Nox1-dependent SMC migration. |
Nox1 knockout mouse-derived SMCs; adenoviral Nox1 re-expression rescue; EGFR inhibitor; ROS measurement; phosphorylation assays; migration assay |
Cardiovascular Research |
High |
22102727
|
| 2011 |
NOX1 is expressed in hepatic stellate cells (but not Kupffer cells) and mediates Ang II-induced profibrogenic effects in liver: NOX1 knockout HSCs had decreased ROS generation and failed to up-regulate collagen α1(I) and TGFβ in response to Ang II. Chimeric mouse studies showed NOX1 mediates profibrogenic effects in endogenous liver cells. |
NOX1 knockout mice; bone marrow chimeras; in vitro HSC activation; ROS measurement; collagen and TGFβ expression assays; hepatic fibrosis models (CCl4, bile duct ligation) |
Hepatology |
High |
21384410
|
| 2011 |
Nox1 mediates morphine-induced analgesic tolerance by regulating GTPase activity and PKC-mediated phosphorylation of RGS9-2, leading to Gαi2/RGS9-2/14-3-3 complex formation: Nox1-/Y mice showed enhanced morphine analgesia, suppressed analgesic tolerance, attenuated morphine-stimulated GTPase activity, abolished PKC translocation, and reduced RGS9-2 phosphorylation and Gαi2/RGS9-2/14-3-3 complex formation. |
Nox1 knockout mice; [35S]GTPγS binding; GTPase activity assay; PKC translocation assay; RGS9-2 phosphorylation; co-immunoprecipitation; opioid receptor binding ([3H]DAMGO) |
The Journal of Neuroscience |
High |
22159121
|
| 2012 |
NOX1 is required for TNFα-induced ROS secretion in intestinal epithelial cells and for suppression of M cell differentiation. NOX1-deficient colonoids exposed to TNFα showed markedly reduced ROS production and induced an M cell transcriptional program; M cell induction was rescued by addition of exogenous H2O2 or paraquat, demonstrating roles for both extra- and intracellular ROS in maintaining epithelial identity. |
NOX1-deficient murine colonoids; TNFα stimulation; ROS measurement; scRNASeq; immunohistochemistry (UEA1); H2O2 and paraquat rescue; in vivo DSS injury model |
Gut |
High |
36191961
|
| 2012 |
NOX1 is involved in endotoxin-induced cardiomyocyte apoptosis through oxidation of Akt cysteine residues and subsequent enhanced Akt-PP2A interaction leading to Akt dephosphorylation: LPS-treated Nox1-/Y mice showed reduced cardiac dysfunction and cardiomyocyte apoptosis, attenuated Akt cysteine oxidation, and reduced Akt-PP2A association compared to wild-type. |
Nox1 knockout mice; LPS and CLP models; caspase-3 activation assay; Akt phosphorylation; Akt cysteine oxidation measurement; Akt-PP2A co-immunoprecipitation |
Free Radical Biology & Medicine |
High |
22982050
|
| 2012 |
Annexin A1 (ANXA1) activates epithelial FPR1 receptors, triggering NOX1-dependent ROS generation which inactivates PTEN and PTP-PEST phosphatases (oxidative inactivation), leading to FAK and paxillin activation and intestinal epithelial cell migration/wound repair. Intestinal epithelial-specific Nox1-/- mice showed defective mucosal wound repair. |
Intestinal epithelial specific Nox1-/- mice; AnxA1-/- mice; phosphatase activity assay; FAK/paxillin phosphorylation; epithelial migration assay; systemic ANXA1 administration |
Journal of Clinical Investigation |
High |
23241962
|
| 2012 |
H2AX increases Nox1 activity partly by reducing the interaction between the Nox1 activator NOXA1 and its inhibitor 14-3-3ζ: DNA damage-induced ROS generation was blocked by Rac1N17 dominant-negative expression and Nox1 siRNA (but not Nox4 siRNA), and H2AX overexpression alone increased Nox1-dependent ROS, placing Nox1 downstream of H2AX in the DNA damage response. |
H2AX overexpression; Nox1 and Nox4 siRNA; Rac1N17 dominant-negative; ROS measurement (NAC, DPI); NOXA1/14-3-3ζ co-immunoprecipitation |
Cell Death & Disease |
Medium |
22237206
|
| 2012 |
AT1 receptor physically associates with Nox1 in vascular smooth muscle cells, and Ang II treatment enhances this binding. Nox1 knockdown attenuated Ang II-induced superoxide generation, NF-κB/AP-1 activation, IL-18 and MMP-9 induction, and SMC migration and proliferation. |
Co-immunoprecipitation (AT1/Nox1); Nox1 siRNA; superoxide measurement; NF-κB/AP-1 reporter assays; SMC migration and proliferation assays; in vivo rat carotid infusion model |
American Journal of Physiology – Heart and Circulatory Physiology |
Medium |
22636674
|
| 2012 |
Extracellular H2O2 enters smooth muscle cells via aquaporin 1 (Aqp1) and activates Nox1-derived superoxide production and Ask1, leading to SMC hypertrophy. Aqp1 siRNA attenuated H2O2 cellular entry and Nox1-dependent superoxide; Nox1 siRNA abrogated Ask1 activation and hypertrophy. |
Nox1 siRNA; Aqp1 siRNA; dominant-negative Ask1 adenovirus; superoxide measurement (EPR, cytochrome c); H2O2 cellular entry assay |
Cardiovascular Research |
Medium |
22997161
|
| 2014 |
Protein kinase C-β1 phosphorylates Nox1 at threonine 429 in response to TNF-α, and this phosphorylation facilitates association of Nox1 with the NoxA1 activation domain, enabling NADPH oxidase complex assembly, ROS production, and VSMC migration. PKCβ1 siRNA abolished TNF-α-mediated ROS and migration; T429 mutagenesis prevented complex assembly. |
Mass spectrometry phosphorylation site identification; site-directed mutagenesis (T429); isothermal titration calorimetry (NoxA1 binding affinity); PKCβ1 siRNA; ROS measurement; VSMC migration assay |
Circulation Research |
High |
25228390
|
| 2014 |
Nox1 is required for GPVI-dependent ROS production in platelets and downstream p38 MAPK activation and TxA2 production, but is not required for platelet aggregation, integrin αIIbβ3 activation, spreading, or granule release. Both Nox1 and Nox2 contribute to collagen-mediated thrombus formation at arterial shear. |
ML171 (Nox1-specific inhibitor); Nox2-deficient mice; CRP agonist activation; TxA2 measurement; p38 MAPK phosphorylation; platelet aggregation; ex vivo perfusion |
Redox Biology |
Medium |
24494191
|
| 2014 |
The MEF2B transcription factor mediates pathological cyclic stretch-induced Nox1 mRNA and protein upregulation in VSMCs, and Nox1-derived ROS drive a phenotypic switch from contractile to synthetic state (increased osteopontin, decreased calponin1 and smoothelin B, increased MMP-9 activity, and enhanced migration). |
MEF2B siRNA; isoform-specific Nox1 inhibitor; Nox1 gene silencing; cyclic stretch apparatus; qPCR; VSMC phenotypic marker assays; MMP-9 activity; migration assay |
Arteriosclerosis, Thrombosis, and Vascular Biology |
Medium |
25550204
|
| 2015 |
NOX1 promotes premature senescence of VSMCs induced by Ang II and zinc via an NF-κB and mitochondrial ROS-dependent transcriptional mechanism: Nox1 siRNA prevented senescence; Nox1 overexpression induced senescence with DNA damage and reduced telomerase. Zinc increased Nox1 protein through mitochondrial ROS → NF-κB → Nox1 transcription pathway, and Nox1 upregulation was zinc-specific compared with other metals. |
Nox1 siRNA; Nox1 overexpression; MitoTEMPO (mitochondrial ROS scavenger); NF-κB inhibition; ZnT3/ZnT10 zinc exporter overexpression; SA-β-gal senescence assay; DNA damage markers |
Free Radical Biology & Medicine |
Medium |
28363602
|
| 2015 |
NOX1 mediates premature senescence in early-stage diabetic kidney by activating PKCα/β translocation and p38 MAPK phosphorylation, leading to p27Kip1 accumulation and DNA damage (γ-H2AX). Nox1-deficient mice showed reduced membranous PKC translocation, PKC activity, p38 phosphorylation, p27Kip1 levels, and γ-H2AX in diabetic kidney. |
Nox1 knockout mice; streptozotocin diabetes model; PKC activity and translocation assays; p38 MAPK phosphorylation; SA-β-gal staining; γ-H2AX immunostaining |
Free Radical Biology & Medicine |
Medium |
25701431
|
| 2016 |
Peroxiredoxin 6 (Prdx6) is a novel binding partner of Noxa1 (Nox activator 1, the Nox1 activator subunit), identified by yeast two-hybrid screening using the Noxa1 SH3 domain as bait. Prdx6 binds to and stabilizes wild-type Noxa1 but not the SH3 domain mutant Noxa1 W436R; Prdx6 knockdown suppresses Nox1 activity; both peroxidase (C47S) and lipase (S32A) mutant forms of Prdx6 fail to support Nox1-dependent superoxide generation or Nox1-mediated cell migration. |
Yeast two-hybrid screening; co-immunoprecipitation; Prdx6 siRNA; Prdx6 mutant overexpression (C47S, S32A); Nox1 activity assay; wound closure migration assay in HCT-116 cells; MJ-33 Prdx6 PLA2 inhibitor |
Free Radical Biology & Medicine |
High |
27094494
|
| 2017 |
Thrombospondin 1 (TSP1), acting through its receptor CD47, activates Nox1 (but not other closely related Nox isoforms) to generate ROS, increase p53 abundance, and drive endothelial senescence via Rb/p21cip. Nox1 inhibition blocked TSP1-induced p53 nuclear localization and p21cip induction; mice lacking TSP1 showed reduced ROS, p21cip, p53 activity, and senescence. |
Nox1 genetic ablation; Nox1 pharmacological inhibitor; CD47 blockade; TSP1 knockout mice; p53/p21cip/Rb assays; senescence assays in human endothelial cells and aged tissue |
Science Signaling |
High |
29042481
|
| 2017 |
NOX1-derived ROS in the ventral tegmental area mediates depressive-like behaviors through redox modification of NMDA receptor subunit NR1: redox proteomics showed NR1 is redox-regulated by NOX1; H2O2 suppressed NMDA-induced BDNF upregulation in NR1-expressing neurons but not in cells expressing cysteine-mutant NR1 (C744A); NOX1 promotes epigenetic silencing (DNA methylation) of bdnf promoter in PFC. |
Nox1 knockout mice; redox proteomics; NR1 C744A mutant expression; miRNA-NOX1 delivery to VTA; BDNF mRNA and DNA methylation assays; chronic social defeat and corticosterone depression models |
The Journal of Neuroscience |
High |
28314819
|
| 2019 |
PDI (protein disulfide isomerase A1) activates Nox1 through a redox-dependent intermolecular disulfide bond between PDI catalytic Cys400 and p47phox Cys196: mass spectrometry confirmed disulfide bonds between PDI and p47phox cysteines; mutation of these cysteines prevented Nox1 complex assembly and VSMC migration. Proximity ligation assay confirmed the PDI-p47phox interaction in murine carotid arteries after wire injury. |
Recombinant protein in vitro interaction; mass spectrometry of crosslinked peptides; site-directed mutagenesis (PDI Cys400, p47phox Cys196); Nox1 complex assembly assay; VSMC migration; proximity ligation assay in vivo |
Arteriosclerosis, Thrombosis, and Vascular Biology |
High |
30580571
|
| 2019 |
NOX1 co-localizes with mTORC1 in VPS41/VPS39-positive lysosomes in colon cancer stem cells. NOX1-derived ROS oxidize S100A9, facilitating its binding to mTORC1 and mTORC1 activation, thereby driving CSC proliferation and colon cancer progression. |
Nox1 siRNA/overexpression in spheroids and organoids; co-localization immunofluorescence; mTORC1 activity assay; S100A9 oxidation measurement; mTORC1-S100A9 co-immunoprecipitation; xenograft tumor models |
Cell Reports |
Medium |
31365870
|
| 2019 |
Hypoxia-induced Nox1 drives endothelial proliferation and migration in pulmonary arterial hypertension through a Nox1-PKA-CREB/Ref-1 signaling pathway that leads to Gremlin1 transcription: ChIP assay showed CREB binding to the Gremlin1 promoter; Nox1 inhibition (NoxA1ds peptide inhibitor or siRNA) abrogated hypoxia-induced PKA activity, CREB phosphorylation, CREB:CRE binding, and Gremlin1 expression. |
Nox1 siRNA; NoxA1ds peptide inhibitor; ChIP assay for CREB:CRE binding; CREB gene silencing; PKA activity assay; EC proliferation and migration; rat PAH model in vivo |
Redox Biology |
Medium |
30802716
|
| 2021 |
NOX1 expression in colonic stem cells is regulated by Toll-like receptor activation in response to microbiota components, and NOX1-derived ROS mediate EGFR activation to drive CSC proliferation. In the absence of NOX1, CSCs fail to generate ROS and have reduced proliferation; the TLR-NOX1-EGFR axis links bacterial sensing to stem cell proliferation. |
NOX1-deficient colonoids and mice; ROS measurement; EGFR inhibition; TLR agonist stimulation; CSC proliferation assay; in vivo germ-free/microbiota experiments |
Cell Reports |
Medium |
33826887
|
| 2021 |
NOX1-derived ROS are critical for spermatogonial stem cell (SSC) self-renewal under normoxia through a ROS-BCL6B-NOX1 feed-forward pathway. Under hypoxia, NOX1-derived ROS are reduced (despite increased mitochondrial ROS), and Nox1-deficient SSCs proliferate poorly under hypoxia but normally under normoxia. NOX1-derived ROS also regulate HIF1A expression in undifferentiated spermatogonia. |
Nox1 knockout mice; SSC culture under normoxia/hypoxia; ROS measurement; BCL6B expression; HIF1A expression; CDKN1A genetic interaction (Cdkn1a-deficient rescue) |
Genes & Development |
Medium |
33446567
|
| 2021 |
Platelet-derived extracellular vesicles (PDEVs) contain Nox1 and generate Nox1-dependent superoxide. PDEV-mediated platelet activation is abrogated by Nox1 inhibition with ML171, establishing Nox1 as a functional enzyme in PDEVs that mediates their platelet-activating capacity. |
Flow cytometry; immunoblot; EPR for superoxide; ML171 Nox1 inhibitor; Nox1 colocalization assay; PDEV platelet activation readout |
Free Radical Biology & Medicine |
Medium |
33548451
|
| 2022 |
BMP4 induces time-dependent physical binding between TLR2 and NOX1 (and TLR2 with NOXO1) in aortic endothelial cells. TLR2 knockout mice were protected from high-fat diet-induced endothelial dysfunction and NOX1-dependent superoxide production, establishing TLR2 as an upstream binding partner required for NOX1 activation in endothelial cells. |
Co-immunoprecipitation (TLR2/NOX1 and TLR2/NOXO1); TLR2 knockout mice; high-fat diet metabolic model; eNOS uncoupling assay; superoxide measurement; endothelium-dependent vasorelaxation |
Diabetes |
Medium |
34127487
|
| 2022 |
Renal NOXA1/NOX1 signaling in the distal nephron regulates epithelial sodium channel (ENaC) expression and Na+ reabsorption during Ang II-induced hypertension: Ang II increased NOXA1/NOX1 expression and ROS in male kidney; Noxa1-deficient mice showed delayed Na+ excretion and blunted ENaC upregulation. Aldosterone induced Nox1-dependent ENaC activity in renal epithelial cells, and Noxa1 siRNA abolished this. |
Noxa1 knockout mice; telemetric blood pressure; Na+ excretion assay; ENaC expression and patch-clamp assay; aldosterone stimulation; Noxa1 siRNA in renal epithelial cells |
Antioxidants & Redox Signaling |
Medium |
34714114
|
| 2005 |
NOXO1 splice variants (NOXO1β and NOXO1γ) differentially regulate Nox family members: both activate Nox1, but NOXO1γ shows a reduced ability to activate Nox3 compared to NOXO1β, establishing that NOXO1 splice forms have distinct functional specificities for different Nox isoforms. |
Expression of purified NOXO1 splice variant proteins; Nox1 and Nox3 activation assays; PX domain lipid-binding assay |
Gene |
Medium |
15949904
|
| 2007 |
GATA-4/5/6, HNF-1α, and Cdx1/Cdx2 transcription factors cooperatively regulate NOX1 transcription by binding a critical promoter element between -422 and -291 in colon epithelial cells. ChIP confirmed physical interaction of GATA-6, HNF-1α, and Cdx2 with this region in intact chromatin; these factors demonstrated cooperativity in transactivating the NOX1 promoter. |
Promoter-reporter deletion analysis; ChIP; EMSA; transcription factor overexpression; real-time PCR; in vivo expression gradient analysis |
Free Radical Biology & Medicine |
Medium |
18005670
|
| 2011 |
RGS2 directly binds STAT3 in the nucleus and suppresses STAT3-mediated Nox1 transcription. TLR2 signaling enhances Nox1 expression through the JAK1/JAK3-STAT3 pathway in a MyD88-independent manner; TLR2 represses RGS2, and Nox1 induction upon RGS2 downregulation is mediated by PKC-η and phospholipase D2. |
RGS2-STAT3 co-immunoprecipitation; GFP-RGS2 nuclear localization imaging; Nox1 promoter reporter; PKC-η and PLD2 inhibitors/knockdown; TLR2 stimulation; JAK inhibitor |
Cellular Signalling |
Medium |
22120521
|
| 2012 |
Nox1-derived ROS in rat REF52 cells and Nox4-derived ROS in human TIG-3 fibroblasts are induced by the Ras/MEK pathway and are required for RasV12-induced premature senescence: Nox1 and Nox4 siRNA blocked RasV12 senescent phenotype (β-galactosidase, growth arrest, p53/p16Ink4a accumulation), DNA damage response, and p38 MAPK activation. Nox1 knockout MEFs confirmed the role of Nox1 in Ras-induced senescence. |
Nox1/Nox4 siRNA; Nox1 knockout MEFs; RasV12 overexpression; SA-β-gal assay; p53/p16Ink4a Western blot; DNA damage and p38 MAPK assays |
Genes to Cells |
Medium |
23216904
|
| 2013 |
Nox1 causes ileocolitis in GPx1/GPx2-double knockout mice: GPx1/GPx2/Nox1 triple knockout male mice were virtually disease-free compared to GPx1/GPx2 DKO mice, with dramatically reduced crypt apoptosis, reduced Ki-67+ crypt epithelium, reduced monocyte/myeloperoxidase staining, and ~8-fold lower TNF cytokine levels in ileum. This establishes Nox1 as the causative source of intestinal oxidative stress and inflammation in this model. |
Triple knockout mice (GPx1/GPx2/Nox1); histological analysis; TUNEL; Ki-67; cleaved caspase-3 immunohistochemistry; TNF cytokine measurement; intestinal length measurement |
Free Radical Biology & Medicine |
High |
24374371
|
| 2017 |
Loss-of-function mutations in NOX1 impair ROS production in colonic epithelium. Validated mutations (p.N122H, p.T497A, p.Y470H, p.R287Q, p.I67M, p.Q293R, p.P330S) reduced ROS production in cell lines, ex vivo colonic explants, and patient-derived colonic organoids. NOX1 constitutively generates high ROS levels in the colonic crypt lumen at the epithelium-microbiota interface. |
Whole-genome and exome sequencing; ROS production assays in cell lines, colonic explants, and patient-derived organoids; NOX1 mutation functional validation |
Mucosal Immunology |
Medium |
29091079
|
| 2018 |
NOX1-derived ROS drive LCN-2 (Lipocalin-2) expression in colonic epithelial cells by controlling IκBζ expression (a master inducer of LCN-2). TNFα + IL-17 induced NOXO1 expression via p38MAPK and JNK1/2, increasing NOX1 activity and ROS; NOX1-deficient mice showed decreased LCN-2 and reduced colon damage during TNBS-induced colitis. |
NOX1-deficient mice; NOXO1 siRNA; p38MAPK/JNK inhibitors; IκBζ expression analysis; LCN-2 measurement; TNBS colitis model |
Mucosal Immunology |
Medium |
30279516
|
| 2019 |
NF-κB directly regulates NOXO1 (the Nox1 organizer subunit) expression in TNF-α-stimulated gastric cancer cells, activating the NOX1 complex and increasing ROS. NOX1/ROS signaling increases SOX2-positive undifferentiated gastric epithelial cells, and disruption of Noxo1 in K19-C2mE mice suppressed metaplastic hyperplasia and decreased SOX2-positive cell numbers. |
NF-κB inhibition; NOXO1 promoter analysis; NOX1/NOXO1 siRNA; in situ hybridization; Noxo1 gene disruption in K19-C2mE mice; SOX2 immunostaining; pharmacological NOX inhibition |
Oncogene |
Medium |
30700829
|
| 2020 |
TSPO is a key upstream regulator of NOX1-dependent neurotoxic ROS production in retinal microglia/phagocytes. Using NADPH oxidase-deficient mice, conditional TSPO deletion in resident microglia (Cx3cr1CreERT2:TSPOfl/fl), and TSPO ligand XBD173 treatment, TSPO was shown to control retinal phagocyte reactivity and subsequent NOX1-dependent neovascularization in a laser-induced AMD model. |
Conditional TSPO knockout mice; NADPH oxidase-deficient mice; tamoxifen-induced Cre-mediated deletion; XBD173 ligand treatment; ROS measurement; neovascularization assay in laser-induced AMD model |
Nature Communications |
Medium |
32483169
|
| 2021 |
NOX1 drives a feedforward inflammatory loop with IL-6 (a SASP component) in vascular senescence: selective NOX1 inhibition in vivo completely reversed age-impaired hind-limb blood flow and angiogenesis while disrupting the NOX1-IL-6 SASP proinflammatory signaling loop. PPARγ down-regulation inversely modulates p65-mediated NOX1 transcription. |
Selective NOX1 inhibitor in aged mice; hind-limb blood flow measurement; angiogenesis assay; IL-6/SASP measurement; PPARγ/p65 transcriptional regulation assay; endothelial cell wound response assay |
PNAS |
Medium |
34654740
|
| 2006 |
NOX1-derived superoxide negatively regulates NGF-induced neurite outgrowth in PC12 cells: NADPH oxidase inhibitors and superoxide scavengers significantly enhanced NGF-induced neurite outgrowth, and stable ribozyme-mediated knockdown of NOX1 mRNA similarly enhanced neurite outgrowth and β-III tubulin expression. NGF induction of NOX1 was mediated via TrkA. |
Stable ribozyme-mediated NOX1 knockdown; NADPH oxidase inhibitors (DPI); superoxide scavengers; neurite length measurement; β-III tubulin expression; PI3K inhibitor studies |
Free Radical Biology & Medicine |
Medium |
16678016
|