PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 26387612-9 2015 Acute restraint stress increased this response in this vessel by mechanisms mediated by Nox4, whose local expression and activity in generating hydrogen peroxide are increased. Hydrogen Peroxide 144-161 NADPH oxidase 4 Rattus norvegicus 88-92 28683591-9 2017 Depletion of HDAC1 or HDAC2 with small interfering RNA (siRNA) attenuated H2O2-induced ROS production and protein carbonylation and elevated FOXO3a protein levels, meanwhile reducing NOX2 and NOX4 protein expression in PC12 cells. Hydrogen Peroxide 74-78 NADPH oxidase 4 Rattus norvegicus 192-196 26918530-10 2016 Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. Hydrogen Peroxide 91-108 NADPH oxidase 4 Rattus norvegicus 146-150 27279484-2 2016 The present study focused on the role of Nox4 and p67phox/Nox2 in the generation of H2O2 and O2 ( -) in the renal medullary thick ascending limb of Henle (mTAL) of SS rats in response to increasing luminal flow (from 5 to 20 nl/min). Hydrogen Peroxide 84-88 NADPH oxidase 4 Rattus norvegicus 41-45 27279484-5 2016 Nox4 was the dominant source of increased intracellular H2O2 production in response to increased luminal flow as determined using the fluorescent dye peroxyfluor 6-AM (PF6-AM). Hydrogen Peroxide 56-60 NADPH oxidase 4 Rattus norvegicus 0-4 27279484-6 2016 The rate of mitochondrial H2O2 production [as determined by mitochondria peroxy yellow 1 (mitoPY1)] was also significantly reduced in SS(Nox4-/-) compared with SS rats, but not in SS(p67phox-/-) rats. Hydrogen Peroxide 26-30 NADPH oxidase 4 Rattus norvegicus 137-145 27279484-9 2016 We conclude that increased mTAL luminal flow results in increases in intracellular and mitochondrial H2O2, which are dependent on the presence of Nox4, and that p67phox/Nox2 accounts solely for increases in O2 ( -) production. Hydrogen Peroxide 101-105 NADPH oxidase 4 Rattus norvegicus 146-150 29971448-8 2018 Results: Cellular injury and oxidant damage were induced after exposure to H2O2 in HCE cells and rat corneas, such as increases of cell death and production of ROS; upregulation of a ROS generation enzyme, NOX4; and downregulation of degradation factors of ROS, superoxide dismutase, catalase, and glutathione S-transferase P. Hydrogen Peroxide 75-79 NADPH oxidase 4 Rattus norvegicus 206-210 29793963-3 2018 The primary source of the renal reactive oxygen species, particularly H2O2, is NADPH oxidase 4 (NOX4). Hydrogen Peroxide 70-74 NADPH oxidase 4 Rattus norvegicus 79-94 29793963-3 2018 The primary source of the renal reactive oxygen species, particularly H2O2, is NADPH oxidase 4 (NOX4). Hydrogen Peroxide 70-74 NADPH oxidase 4 Rattus norvegicus 96-100 29793963-4 2018 We hypothesized that NOX4-derived H2O2 contributes to podocyte damage in DKD via elevation of podocyte calcium.Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SSNox4-/-) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6. Hydrogen Peroxide 34-38 NADPH oxidase 4 Rattus norvegicus 21-25 29655699-11 2018 In H2O2 injured-HUVECs the deleterious alterations in ROS levels and antioxidant enzymes activity were reversed by scutellarin and the mRNA and protein expression of SOD1 and Nox4 were restored also. Hydrogen Peroxide 3-7 NADPH oxidase 4 Rattus norvegicus 175-179 28063381-7 2017 Moreover, Nox4, which is constitutively active in renal cells and is involved in the generation of hydrogen peroxide, was up-regulated during UUO-mediated fibrosis and induced by TGF-beta1 in HK-2 cells, and this up-regulation could be blunted by Brd4 inhibition. Hydrogen Peroxide 99-116 NADPH oxidase 4 Rattus norvegicus 10-14 26387612-11 2015 Taken together, our findings suggest that acute restraint stress exacerbates the contractile hyperreactivity to angiotensin II in diabetic rat carotid by enhancing Nox4-driven generation of hydrogen peroxide, which evokes contractile tone by cyclooxygenases-dependent mechanisms. Hydrogen Peroxide 190-207 NADPH oxidase 4 Rattus norvegicus 164-168 26136558-1 2015 The presence of NADPH oxidase (Nox) in the kidney, especially Nox4, results in H2O2 production, which regulates Na(+) excretion and urine formation. Hydrogen Peroxide 79-83 NADPH oxidase 4 Rattus norvegicus 62-66 26136558-3 2015 The present study tested whether H2O2 derived from Nox4 affects TRPV1 function in renal sensory responses. Hydrogen Peroxide 33-37 NADPH oxidase 4 Rattus norvegicus 51-55 26136558-10 2015 Interestingly, immunofluorescence labeling demonstrated that Nox4 colocalizes with TRPV1 in sensory fibers of the renal pelvis, indicating that H2O2 generated from Nox4 may affect TRPV1 activity. Hydrogen Peroxide 144-148 NADPH oxidase 4 Rattus norvegicus 61-65 26136558-10 2015 Interestingly, immunofluorescence labeling demonstrated that Nox4 colocalizes with TRPV1 in sensory fibers of the renal pelvis, indicating that H2O2 generated from Nox4 may affect TRPV1 activity. Hydrogen Peroxide 144-148 NADPH oxidase 4 Rattus norvegicus 164-168 26136558-13 2015 Overall, these results suggest that Nox4-positive fibers liberate H2O2 after mechanostimulation, thereby contributing to a renal sensory nerve-mediated diuretic/natriuretic response. Hydrogen Peroxide 66-70 NADPH oxidase 4 Rattus norvegicus 36-40 25203114-10 2014 Moreover, external ROS (H2O2 100 microM, 24 h) rescued the effects of NOX4 knockdown, which included the declining of TRPC1 and 6 expression, basal intracellular calcium concentration ([Ca2+]i) and store-operated calcium entry (SOCE), suggesting that NOX4 plays as an important mediator in BMP4-induced proliferation and intracellular calcium homeostasis. Hydrogen Peroxide 24-28 NADPH oxidase 4 Rattus norvegicus 70-74 25450615-6 2015 We investigated the molecular mechanisms which underlie this more proliferative phenotype in isolated neonatal rat cardiomyocytes (NRCs) in vitro, and demonstrate that Nox4 overexpression mediates an H2O2-dependent activation of the ERK1/2 signalling pathway, which in turn phosphorylates and activates the transcription factor c-myc. Hydrogen Peroxide 200-204 NADPH oxidase 4 Rattus norvegicus 168-172 25595661-6 2015 Based on this, we aimed to investigate: (1) the role of the TGFbeta1/ALK5-Nox4-H2O2 pathway on modulating Mas signaling in diabetic rat contralateral carotid; and (2) the contribution of Mas signaling in the control of local blood flow. Hydrogen Peroxide 79-83 NADPH oxidase 4 Rattus norvegicus 74-78 25595661-8 2015 TGFbeta1/ALK5 activation enhanced Nox4 expression and Nox4-driven generation of H2O2. Hydrogen Peroxide 80-84 NADPH oxidase 4 Rattus norvegicus 54-58 25203114-10 2014 Moreover, external ROS (H2O2 100 microM, 24 h) rescued the effects of NOX4 knockdown, which included the declining of TRPC1 and 6 expression, basal intracellular calcium concentration ([Ca2+]i) and store-operated calcium entry (SOCE), suggesting that NOX4 plays as an important mediator in BMP4-induced proliferation and intracellular calcium homeostasis. Hydrogen Peroxide 24-28 NADPH oxidase 4 Rattus norvegicus 251-255 23718778-5 2013 NSAID-mediated rise of H2O2 was abrogated in adipocyte plasma membranes by: diphenyleneiodonium, an inhibitor of NADPH oxidase (NOX); the NOX4 antibody; and cytochrome c, trapping the NOX-formed superoxide. Hydrogen Peroxide 23-27 NADPH oxidase 4 Rattus norvegicus 138-142 23771688-4 2013 Cardiac Nox2 protein expression increased 40% in OLETF compared with age-matched, lean, strain-control Long Evans Tokushima Otsuka (LETO) rats, while mRNA and protein expression of the H2O2-producing Nox4 increased 40-100%. Hydrogen Peroxide 185-189 NADPH oxidase 4 Rattus norvegicus 200-204 23619128-7 2013 Short-interfering RNA-mediated knockdown of NOS-1 or NOX4 attenuated increased nitric oxide and H2O2 content, respectively, in stretched-cell-conditioned medium. Hydrogen Peroxide 96-100 NADPH oxidase 4 Rattus norvegicus 53-57 23718778-10 2013 CONCLUSIONS: NSAIDs activate NOX4 in adipocytes to produce H2O2, which impairs cAMP-dependent PKA-II activation, thus preventing isoproterenol-activated lipolysis. Hydrogen Peroxide 59-63 NADPH oxidase 4 Rattus norvegicus 29-33 23033809-1 2013 BACKGROUND: Dual oxidases (DUOX1 and DUOX2) are NADPH oxidases (NOX) involved in hydrogen peroxide production necessary for thyroid hormonogenesis, but recently, the NOX4 has also been described in the thyroid gland. Hydrogen Peroxide 81-98 NADPH oxidase 4 Rattus norvegicus 166-170 23407453-6 2013 In the thyroids of the DM rats, we found increased H(2)O(2) generation due to higher DUOX protein content and DUOX1, DUOX2, and NOX4 mRNA expressions. Hydrogen Peroxide 51-59 NADPH oxidase 4 Rattus norvegicus 128-132 23164764-10 2013 Moreover, siRNA-mediated knockdown of p47phox, Nox2 and Nox4 inhibited H(2)O(2)-induced NADPH oxidase activity. Hydrogen Peroxide 71-79 NADPH oxidase 4 Rattus norvegicus 56-60 23164764-11 2013 H(2)O(2)-induced collagen synthesis and fibronectin expression were also inhibited by p47phox, Nox2 and Nox4 knock down. Hydrogen Peroxide 0-8 NADPH oxidase 4 Rattus norvegicus 104-108 22736614-10 2012 In the H2O2-induced rat corneal epithelium, SA3K alleviated the oxidative stress and downregulated NOX4 and NRF2. Hydrogen Peroxide 7-11 NADPH oxidase 4 Rattus norvegicus 99-103 18760347-0 2008 Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Hydrogen Peroxide 86-103 NADPH oxidase 4 Rattus norvegicus 27-31 21316443-3 2011 In the renal cortex of 3-month old SHR increases in hydrogen peroxide (H(2)O(2)) were accompanied by augmented expression of NADPH oxidase subunit Nox4 and decreased expression of antioxidant enzymes SOD1 and SOD3. Hydrogen Peroxide 52-69 NADPH oxidase 4 Rattus norvegicus 147-151 18760347-5 2008 We hypothesized that Nox1 and Nox4 play distinct roles in basal and angiotensin II (AngII)-stimulated production of O2*- and H2O2. Hydrogen Peroxide 125-129 NADPH oxidase 4 Rattus norvegicus 30-34 18760347-11 2008 Depletion of Nox4 in RASMCs led to diminished basal H2O2 production, but did not affect O2*- or H2O2 production stimulated by AngII. Hydrogen Peroxide 52-56 NADPH oxidase 4 Rattus norvegicus 13-17 18760347-13 2008 Our data suggest that Nox4 produces mainly H2O2, while Nox1 generates mostly O2*- that is later converted to H2O2. Hydrogen Peroxide 43-47 NADPH oxidase 4 Rattus norvegicus 22-26 18760347-13 2008 Our data suggest that Nox4 produces mainly H2O2, while Nox1 generates mostly O2*- that is later converted to H2O2. Hydrogen Peroxide 109-113 NADPH oxidase 4 Rattus norvegicus 22-26 18760347-14 2008 Therefore, Nox4 is responsible for basal H2O2 production, while O2*- production in nonstimulated and AngII-stimulated cells depends on Nox1. Hydrogen Peroxide 41-45 NADPH oxidase 4 Rattus norvegicus 11-15 34450166-11 2021 In vitro studies showed that Nox4 inhibitor enhanced arteriolar response to NE and reduced hydrogen peroxide (H2O2) level in cirrhotic rats. Hydrogen Peroxide 91-108 NADPH oxidase 4 Rattus norvegicus 29-33 33794383-3 2021 NOX4 generates H2O2, which can activate the transient receptor potential melastatin 2 (TRPM2) channels, providing Ca2+ signals for cell proliferation and migration. Hydrogen Peroxide 15-19 NADPH oxidase 4 Rattus norvegicus 0-4 34450166-11 2021 In vitro studies showed that Nox4 inhibitor enhanced arteriolar response to NE and reduced hydrogen peroxide (H2O2) level in cirrhotic rats. Hydrogen Peroxide 110-114 NADPH oxidase 4 Rattus norvegicus 29-33 35158330-3 2021 Nrf2 is activated by H2O2-producing Nox4 and nitric oxide (NO), but also induces NADPH oxidase 4 (Nox4) and endothelial nitric oxide synthase (eNOS). Hydrogen Peroxide 21-25 NADPH oxidase 4 Rattus norvegicus 36-40 35158330-3 2021 Nrf2 is activated by H2O2-producing Nox4 and nitric oxide (NO), but also induces NADPH oxidase 4 (Nox4) and endothelial nitric oxide synthase (eNOS). Hydrogen Peroxide 21-25 NADPH oxidase 4 Rattus norvegicus 81-96 35158330-3 2021 Nrf2 is activated by H2O2-producing Nox4 and nitric oxide (NO), but also induces NADPH oxidase 4 (Nox4) and endothelial nitric oxide synthase (eNOS). Hydrogen Peroxide 21-25 NADPH oxidase 4 Rattus norvegicus 98-102 32802129-6 2020 BYHWD significantly increased cell viability, inhibited apoptosis, induced vascular tube formation, decreased intracellular ROS generation, and reduced Nox activity and Nox4 protein expression in H2O2-treated HUVECs in a dose-dependent manner. Hydrogen Peroxide 196-200 NADPH oxidase 4 Rattus norvegicus 169-173 33584299-0 2020 USP7 Inhibition Alleviates H2O2-Induced Injury in Chondrocytes via Inhibiting NOX4/NLRP3 Pathway. Hydrogen Peroxide 27-31 NADPH oxidase 4 Rattus norvegicus 78-82 32898512-6 2020 Specifically, NOX4 expression was higher (90%, p < 0.05), suggesting that it could be a source of H2O2. Hydrogen Peroxide 98-102 NADPH oxidase 4 Rattus norvegicus 14-18 33154672-8 2020 Down-regulating the expression of NOX4 in rats can reduce the level of H2O2 and nNO in dorsal horn tissue, and increase the expression of SOD to reduce the oxidative stress response. Hydrogen Peroxide 71-75 NADPH oxidase 4 Rattus norvegicus 34-38 32475313-2 2020 In SS rats, high-salt intake is known to increase the renal production of H2O2 by NOX4, the most abundant NOX isoform in the kidney, and the global knockout of NOX4 blunts salt-sensitivity in these rats. Hydrogen Peroxide 74-78 NADPH oxidase 4 Rattus norvegicus 82-86 32475313-2 2020 In SS rats, high-salt intake is known to increase the renal production of H2O2 by NOX4, the most abundant NOX isoform in the kidney, and the global knockout of NOX4 blunts salt-sensitivity in these rats. Hydrogen Peroxide 74-78 NADPH oxidase 4 Rattus norvegicus 160-164 32475313-8 2020 Given the direct activation of mTORC1 by H2O2 and absence of any further protection from salt-induced hypertension in rapamycin-treated SSNox4-/- rats, we conclude that NOX4-H2O2 is a major upstream activator of mTORC1 that contributes importantly to salt-induced hypertension and renal injury in the SS rat model. Hydrogen Peroxide 174-178 NADPH oxidase 4 Rattus norvegicus 169-173 32475313-3 2020 Here, we explored the hypothesis that elevations of H2O2 by NOX4 in high-salt fed SS rat stimulate mTORC1 for the full development of salt-induced hypertension and renal injury. Hydrogen Peroxide 52-56 NADPH oxidase 4 Rattus norvegicus 60-64 31370714-5 2019 Mechanically, NOX4-generated H2O2 was the inducer of oxidative stress, Ca2+ homeostasis disorder, and ER stress in EGCs upon TcdB treatment, and NOX4 inhibition protected EGCs against TcdB toxicity via attenuating these dysfunctions. Hydrogen Peroxide 29-33 NADPH oxidase 4 Rattus norvegicus 14-18 31563085-7 2020 Nox4 was down-regulated in renal arteries and Nox4-dependent H2O2 generation and endothelial relaxation were reduced in OZR. Hydrogen Peroxide 61-65 NADPH oxidase 4 Rattus norvegicus 46-50