Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
malfunction
-
inhibition of NAD(P)H oxidase abolishes endothelial dysfunction in AMP-activated protein kinase alpha2-deficient mice
malfunction
-
isozyme Nox4 is involved in a variety of diseases such as idiopathic pulmonary fibrosis, pulmonary arterial hypertension, diabetic nephropathy, and complications such as diabetic cardiomyopathy and neuropathy and retinopathy or cancers like metastatic renal cell carcinoma
malfunction
-
lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreases Ang2 mRNA levels and greatly impairs hemangioma growth in vivo
malfunction
-
mice deficient in NOX4 of either sex, but not those deficient for NOX1 or NOX2, are largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia
malfunction
-
NAD(P)H oxidase inhibition by apocynin might suppress reactive oxygen species production and confer neuroprotection in premature infants with intraventricular hemorrhage
malfunction
-
the inhibition of NAD(P)H oxidase-dependent nuclear factor-kappa B signaling reduces the increase in monocyte chemoattractant protein-1 production by glomerular endothelial cells induced by angiotensin II
malfunction
-
the inhibition of NADPH oxidase may contribute to lowered rate of renal gluconeogenesis, probably due to decreasing phosphoenolpyruvate carboxykinase activity
malfunction
-
the inhibition of NADPH oxidase may contribute to lowered rate of renal gluconeogenesis, probably due to decreasing phosphoenolpyruvate carboxykinase activity
malfunction
-
blockade of NAD(P)H oxidase with apocynin or superoxide dismutationwith PEG-SOD prevents the increment in superoxide and changes in P-eNOSThr495 observed during apamin and triarylmethane-34 application
malfunction
-
DelTASsnox1 strains have reduced reactive oxygen species levels, are unable to develop sclerotia, and unexpectedly correlate with significantly reduced oxalate production. Inactivation of the Nox2 gene results in limited sclerotial development, but the organism remains fully pathogenic
malfunction
-
excessive NADPH oxidase activation and reactive oxygen species overproduction are believed to participate in disorders such as joint, lung, vascular and intestinal inflammation
malfunction
-
in pathological circumstances, excess Nox2 can lead to oxidative stress and disease development. NOX2 V204A mutant is a competitive inhibitor of wild-type p67phox. Binding of the PB1 domain of NOX2 to p40phox is abolished by a K355A mutation in NOX2. Depletion or mutation of p40phox impairs reactive oxygen species production in neutrophils and endothelial cells. Upregulation of Nox1 can lead to oxidative stress in the cardiovascular system
malfunction
-
specific inhibition of NOX by transfection of siRNA against p22phox mRNA effectively blocks low-density lipoprotein- or glycated low-density lipoprotein-induced increases in p22phox, NOX4, PAI-1, and HSF1 in wild-type mouse embryonic fibroblasts
malfunction
-
a lesion in BLI-3's NADPH oxidase domain increases sensitivity to pathogen and diminishes lifespan
malfunction
-
phagocyte NADPH oxidase deficiency causes chronic granulomatous disease
malfunction
-
blockade of NAD(P)H oxidase with apocynin or superoxide dismutationwith PEG-SOD prevents the increment in superoxide and changes in P-eNOSThr495 observed during apamin and triarylmethane-34 application
-
malfunction
-
DelTASsnox1 strains have reduced reactive oxygen species levels, are unable to develop sclerotia, and unexpectedly correlate with significantly reduced oxalate production. Inactivation of the Nox2 gene results in limited sclerotial development, but the organism remains fully pathogenic
-
malfunction
-
specific inhibition of NOX by transfection of siRNA against p22phox mRNA effectively blocks low-density lipoprotein- or glycated low-density lipoprotein-induced increases in p22phox, NOX4, PAI-1, and HSF1 in wild-type mouse embryonic fibroblasts
-
metabolism
-
mechanisms involved in the control of NO production involving the enzyme, NADPHox-mediated superoxide formation is involved in the inhibition of NO production, overview
metabolism
-
tight regulation, critical to avoid excessive production of deleterious superoxide, is evident from the large number of proteins involved in oxidase assembly. These include Nox2 itself, p22phox, p47phox, p67phox, and p40phox, all essential subunits whose mutations can cause CGD Also crucial is Rac GTPase, which binds p67phox and the dehydrogenase domain of Nox2. In the resting state, Nox2 and p22phox form an inactive membrane complex known as cytochrome b558. Product superoxide is the first reactive oxygen species in a cascade of metabolites including hydrogen peroxide and peroxynitrite
metabolism
the enzyme plays an important role in host defense system by catalyzing the production of superoxide anions
metabolism
-
mechanisms involved in the control of NO production involving the enzyme, NADPHox-mediated superoxide formation is involved in the inhibition of NO production, overview
-
physiological function
-
cardiovascular NAD(P)H oxidases play important roles in physiological processes such as blood pressure regulation as well as pathophysiological events including hypertension and atherosclerosis
physiological function
-
cardiovascular NAD(P)H oxidases play important roles in physiological processes such as blood pressure regulation as well as pathophysiological events including hypertension and atherosclerosis
physiological function
-
cardiovascular NAD(P)H oxidases play important roles in physiological processes such as blood pressure regulation as well as pathophysiological events including hypertension and atherosclerosis
physiological function
-
cathepsin L-derived endostatin, if excessive, may result in endothelial dysfunction through enhanced production of O2- due to NAD(P)H oxidase activation
physiological function
-
germinal matrix hemorrhage-intraventricular hemorrhage, by induction of NAD(P)H oxidases, may cause oxidative/nitrosative stress contributing to brain injuries. Activation of NAD(P)H oxidase is the predominant mechanism of free-radical generation in pups with intraventricular hemorrhage
physiological function
-
in skeletal muscle and in heart the NADPH oxidase system is mainly involved in oxidative stress
physiological function
-
increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes
physiological function
-
NAD(P)H derived superoxide generation is the underlying cause of vasoactive dysfunction in hyperglycemic Goto-Kakizaki arteries
physiological function
-
NAD(P)H oxidase activity promotes cellular hypoxia (nonspecific reduction of metronidazole)
physiological function
-
NAD(P)H oxidase is the main source of reactive oxygen species in diabetic podocytes and their production contributes to the development of diabetic nephropathy
physiological function
-
NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
-
NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
-
NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
-
NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
-
NAD(P)H oxidase-derived reactive oxygen species play a role in the development and progression of atherosclerosis
physiological function
-
NADPH oxidase is a major source of reactive oxygen species in aortas of spontaneously hypertensive rats
physiological function
-
Nox4 is a critical regulator of hemangioma growth
physiological function
-
oxidative stress is dependent on the upregulation of NAD(P)H oxidase 4, a reactive oxygen species Nox homologue, triggering endoplasmic reticulum stress. The endoplasmic reticulum stress pathway through activation of Nox4 by integrins alpha1beta1 plays a key role in 3-deoxyglucosone-collagen-induced caspase-3 activation, which may play an important role in the pathogenesis of diabetic wounds
physiological function
-
the 28000 Da NOX4 isoform has a key role in toll-like receptor 4-mediated apoptosis during renal ischemia/reperfusion injury. NOX4 controls Jun N-terminal kinase-mediated renal tubule cell apoptosis induced by hypoxia
physiological function
while macula densa cells express the NOX2 and NOX4 isoforms, NOX 2 is primarily responsible for NaCl-induced O2- generation
physiological function
-
blockade of small-conductance and intermediate-conductance Ca2+-activated K+ channels activates NAD(P)H oxidase-dependent superoxide formation, which leads to inhibition of NO release through P-eNOSThr495
physiological function
-
fungal NADPH oxidases are required for pathogenic development and are consistent with the importance of reactive oxygen species regulation in the successful pathogenesis of Sclerotinia sclerotiorum. Central role for SsNox1 in both virulence and pathogenic (sclerotial) development
physiological function
-
NADPH oxidase enzymes are critical mediators of cardiovascular physiology and pathophysiology. They are expressed in virtually all cardiovascular cells, and regulate such diverse functions as differentiation, proliferation, apoptosis, senescence, inflammatory responses and oxygen sensing. They target a number of important signaling molecules, including kinases, phosphatases, transcription factors, ion channels, and proteins that regulate the cytoskeleton. On activation, Nox2 uses NADPH to reduce molecular oxygen to superoxide anion, which, in concert with its metabolites, is used by phagocytes to destroy invading microorganisms. Nox organizers include both p47phox and its homologue, Noxo1, whereas Nox activators comprise p67phox and the structurally similar Noxa1. Because Nox2 and Nox1 are closely related, both enzymes can be activated in transfected cells by various organizer and activator pairs. Nox1 plays a host defensive role in colon epithelium. primary biochemical function of vascular Nox1 is superoxide production, which is then rapidly converted to hydrogen peroxide. The moderate physiological activity of Nox1, compared with the phagocytic Nox2, can be attributed to its low expression as well as specific regulatory subunits and signaling cascades. Nox4 is a constitutively active enzyme mostly regulated by transcription. Role of enzyme complex component p22phox, detailed overview. Nox4 can produce a higher hydrogen peroxide to superoxide ratio than Nox1 and Nox2. Isozyme Nox5S may be constitutively active or be a competitive inhibitor of calcium-dependent activation when present in the same tetrameric complex as Nox5L
physiological function
Nox1 relates production of reactive oxygen species to specific biocontrol activity against Pythium ultimum, but not Botrytis cinerea or Rhizoctonia solani
physiological function
-
reactive oxygen species production by the phagocyte NADPH oxidase is essential for host defenses against pathogens. Reactive oxygen species are very reactive with biological molecules such as lipids, proteins and DNA, potentially resulting in cell dysfunction and tissue insult. Enzyme component P47phox is phosphorylated on multiple sites located in its carboxy-terminal portion, including serines 303-379, which play a central role in NADPH oxidase activation and regulation. In human neutrophils, various protein kinases have been implicated in the activation of NADPH oxidase, among which the PKC and MAP kinase families appear to play a major role
physiological function
-
regulatory role of NADPH oxidase in glycated low-density lipoprotein-induced upregulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts and diabetic mice, overview. NOX4 plays a crucial role in glycated low-density lipoprotein-induced expression of HSF1andPAI-1 in mouse fibroblasts
physiological function
-
the activity of NOX5 appears to be regulated by a self-contained Ca2+ binding domain, the conformational change of the domain upon Ca2+ binding is essential for domain-domain interaction and superoxide production
physiological function
-
NADPH oxidase is responsible for H2O2 level regulation in vascular cylinder cells
physiological function
-
NADPH oxidase NOX4 is a critical mediator of BRAF(V600E)-induced downregulation of the sodium/iodide symporter in papillary thyroid carcinomas
physiological function
-
the enzyme BLI-3 has roles in both cuticle development and in protection against infection with Enterococcus faecalis
physiological function
-
the enzyme functions in root hair initiation and elongation
physiological function
-
the enzyme plays a significant role in promoting post-injury inflammation after spinal cord injury
physiological function
-
the enzyme promotes long-term persistence of oxidative stress after an exposure to irradiation. Enzyme-dependent H2O2 production, which induces DNA double-strand breaks, can cause genomic instability and promote the generation of neoplastic cells through its mutagenic effect
physiological function
NADPH oxidases (NOX2/NOX4) and inducible nitric oxide synthase (iNOS) derived oxidative stress play a key role in psoriasis induced kidney dysfunction. NADPH oxidase (NOX2 and NOX4) isoforms, and inducible nitric oxidase synthase (iNOS) are elevated in the renal tissue under inflammatory conditions such as acute kidney injury and chronic kidney disease. These enzymes are capable of producing reactive oxygen species (ROS) in large quantities under inflammatory conditions, which may cause oxidative damage to biological macromolecules such as lipids, proteins and nucleic acids leading to malfunction of cellular structures through dysregulation of ion pumps, and enzymatic activity
physiological function
five days following Sclerotina sclerotiorum inoculation, wild-type soybean plants show typical Sclerotinia stem rot symptoms and begin to wilt. RBOHL-silenced plants do not show any wilting symptoms, lesion development is arrested shortly after reaching the main stem, and a red/dark discoloration is apparent at the edge of the lesion. The overexpression of isoforms RBOHB, RBOHL, RBOHP and RBOHQ in Nicotiana benthamiana leaf enhances disease development following Sclerotina sclerotiorum inoculation to varying levels and results in an approximately 40%-60% increase in lesion area compared with empty vector control leaves
physiological function
five days following Sclerotina sclerotiorum inoculation, wild-type soybean plants show typical Sclerotinia stem rot symptoms and begin to wilt. RBOHP-silenced plants do not show any wilting symptoms, lesion development is arrested shortly after reaching the main stem, and a red/dark discoloration is apparent at the edge of the lesion. The overexpression of isoforms RBOHB, RBOHL, RBOHP and RBOHQ in Nicotiana benthamiana leaf enhances disease development following Sclerotina sclerotiorum inoculation to varying levels and results in an approximately 40%-60% increase in lesion area compared with empty vector control leaves
physiological function
five days following Sclerotina sclerotiorum inoculation, wild-type soybean plants show typical Sclerotinia stemrot symptoms and begin to wilt. RBOHQ-silenced plants do not show any wilting symptoms, lesion development is arrested shortly after reaching the main stem, and a red/dark discoloration is apparent at the edge of the lesion. The overexpression of isoforms RBOHB, RBOHL, RBOHP and RBOHQ in Nicotiana benthamiana leaf enhances disease development following Sclerotina sclerotiorum inoculation to varying levels and results in an approximately 40%-60% increase in lesion area compared with empty vector control leaves
physiological function
NOX2 is ubiquitously expressed in acute myeloid leukemia blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages. It is less expressed in leukemic stem cells and in relapsed acute myeloid leukemia. No endogenous NOX activity is detected in the absence of phorbol 12-myristate 13-acetate stimulation. Cytochrome b-245 heavy chain knockdown hampers induced NOX2 activity, but does not affect the proliferation and differentiation of THP-1 and HL-60 cells
physiological function
NOX5 overexpression induces changes in the expression of the unfolded protein response components, which are associated with increased apoptosis. 298 genes are differentially expressed in the overexpression line. In endothelial-specific NOX5 knock-in mice, changes in the expression of the unfolded protein response components genes are observed. In these animals, significant associations between the unfolded protein response components gene expression and echocardiographic parameters are found
physiological function
-
treatment with Cr(VI) elicits H2O2 production in plants, which is suppressed by NaHS and also by an inhibitor of NADPH oxidase (NOX). These effects are correlated with relative changes in carbomyl and thiol groups
physiological function
-
blockade of small-conductance and intermediate-conductance Ca2+-activated K+ channels activates NAD(P)H oxidase-dependent superoxide formation, which leads to inhibition of NO release through P-eNOSThr495
-
physiological function
-
fungal NADPH oxidases are required for pathogenic development and are consistent with the importance of reactive oxygen species regulation in the successful pathogenesis of Sclerotinia sclerotiorum. Central role for SsNox1 in both virulence and pathogenic (sclerotial) development
-
physiological function
-
NAD(P)H oxidase activity promotes cellular hypoxia (nonspecific reduction of metronidazole)
-
physiological function
-
regulatory role of NADPH oxidase in glycated low-density lipoprotein-induced upregulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts and diabetic mice, overview. NOX4 plays a crucial role in glycated low-density lipoprotein-induced expression of HSF1andPAI-1 in mouse fibroblasts
-
physiological function
-
Nox1 relates production of reactive oxygen species to specific biocontrol activity against Pythium ultimum, but not Botrytis cinerea or Rhizoctonia solani
-
additional information
-
active phagocyte NADPH oxidase is a multicomponent enzyme complex composed of six proteins: p22phox (phox: phagocyte oxidase), gp91phox/NOX2, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2
additional information
-
for the activation of Nox enzymes, cytosolic regulatory components (Rac, p67phox, p47phox, and p40phox) are recruited into the integral membrane protein flavocytochrome b558, consisting of the catalytic subunits gp91phox and p22phox
additional information
-
Nox5 is similar to other Nox enzymes, with 6 transmembrane helices expected to bind 2 hemes and a cytosolic dehydrogenase domain including FAD and NADPH binding sites, but neither Nox5 isoform appears to require cytosolic subunits or p22phox. Presence of an additional cytosolic N-terminal segment, containing 4 calcium binding EF-hands in Nox5. Nox4 activity is constitutive, isozyme Nox4D appears to be fully active, although it lacks most of the transmembrane domain, it might retain activity by coupling to electron acceptors, such as cytochrome c in mitochondria, which might also be an alternative route of hydrogen peroxide formation by full-length Nox4. Nox4, Nox1 and Nox2 bind to p22phox, the interaction is abolished by mutation of heme-binding histidine 115. Nox2 is composed of two main domains of equal sizes with very different properties. The amino-terminal moiety includes six transmembrane alpha-helices I-VI connected by 5 loops A-E. Because both N- and C-termini are cytosolic, 3 loops are extracellular and include consensus asparagine glycosylation sites, whereas the other 2 are intracellular and accessible to cytosolic regulators. The cytosolic carboxy-terminal moiety of Nox2 constitutes a dehydrogenase domain that includes consensus binding sites for its NADPH substrate and FAD cofactor, activation domain of p67phox triggers FAD reduction by Nox2. A charge compensation mechanism, required to balance electron transport by Nox2 and sustain its activity, is provided by a voltage-gated proton channel8 and the chloride/proton antiporter ClC-3. The first SH3 domain of NOX2 increases oxidase activity, the NOX2 PB1 domain allows binding to p40phox. The C-terminal SH3 domain of p67phox of NOX2 is responsible for binding the proline-rich region of p47phox and therefore allows p67phox translocation to the membrane after activation. The C-terminal PB1 domain of p40phox interacts with the PB1 domain of p67phox. Nox1, like Nox2, associates with p22phox to form a membrane-bound cytochrome
additional information
mechanistic computational model, which incorporates a generalized random rapid equilibrium binding mechanism for NOX2 assembly and activation as well as regulations by GTP (activation), GDP (inhibition), and individual subunits enhancing the binding of other subunits (mutual binding enhancement). The model replicates diverse published kinetic data. The model provides a mechanistic, quantitative, and integrated framework for investigating the critical roles of NOX2 subunits in NOX2 assembly and activation facilitating ROS production in a variety of physiological and pathophysiological conditions
additional information
-
for the activation of Nox enzymes, cytosolic regulatory components (Rac, p67phox, p47phox, and p40phox) are recruited into the integral membrane protein flavocytochrome b558, consisting of the catalytic subunits gp91phox and p22phox
-