Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.99.6 (NADPH oxidase)
10,295 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Green tea (GT), through its antioxidant properties, may be useful to treat or prevent human diseases. Because several lines of evidence suggest that oxidative stress contributes to the pathogenesis of diabetic nephropathy, we tested the hypothesis that GT prevents diabetes and hypertension-related renal oxidative stress, attenuating renal injury. Spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes and nondiabetic SHR were treated daily with tap water or freshly prepared GT (13.3 g/L). After 12 wk, the systolic blood pressure did not differ between treated and untreated nondiabetic or diabetic rats. However, body weight was less (P < 0.05) and glycemia was greater in diabetic SHR rats than in nondiabetic rats. Renal oxidative stress variables such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine expression, NADPH oxidase-dependent superoxide generation, and the expression of renal cortex Nox4 were greater (P < 0.05) in diabetic rats that received water (DW) than in nondiabetic rats that received water (CW). The 8-OHdG and NADPH oxidase-dependent superoxide generation were significantly less in rats treated with GT. Nitrotyrosine and Nox4 expression were significantly less in diabetic rats that received GT (DGT) than in DW. Likewise, the indices of renal injury, albuminuria, and renal expression of collagen IV were significantly greater in DW than in CW. These differences were significantly less in DGT than in DW. GT reestablished the redox state and reduced the indicators of nephropathy without altering glycemia and blood pressure levels in diabetic SHR. These findings suggest that the consumption of GT may ameliorate nephropathy in diabetic hypertensive patients.
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PMID:Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats. 1905 45

Methanocaldococcus jannaschii, a deeply rooted hyperthermophilic anaerobic methanarchaeon from a deep-sea hydrothermal vent, carries an NADH oxidase (Nox) homologue (MJ0649). According to the characteristics described here, MJ0649 represents an unusual member within group 3 of the flavin-dependent disulfide reductase (FDR) family. This FDR group comprises Nox, NADH peroxidases (Npx) and coenzyme A disulfide reductases (CoADRs); each carries a Cys residue that forms Cys-sulfenic acid during catalysis. A sequence analysis identified MJ0649 as a CoADR homologue. However, recombinant MJ0649 (rMJNox), expressed in Escherichia coli and purified to homogeneity an 86 kDa homodimer with 0.27 mol FAD (mol subunit)(-1), showed Nox but not CoADR activity. Incubation with FAD increased FAD content to 1 mol (mol subunit)(-1) and improved NADH oxidase activity 3.4-fold. The FAD-incubated enzyme was characterized further. The optimum pH and temperature were > or =10 and > or =95 degrees C, respectively. At pH 7 and 83 degrees C, apparent Km values for NADH and O2 were 3 microM and 1.9 mM, respectively, and the specific activity at 1.4 mM O2 was 60 micromol min(-1) mg(-1); 62 % of NADH-derived reducing equivalents were recovered as H2O2 and the rest probably generated H2O. rMjNox had poor NADPH oxidase, NADH peroxidase and superoxide formation activities. It reduced ferricyanide, plumbagin and 5,5'-dithiobis(2-nitrobenzoic acid), but not disulfide coenzyme A and disulfide coenzyme M. Due to a high Km, O2 is not a physiologically relevant substrate for MJ0649; its true substrate remains unknown.
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PMID:Characterization of an NADH oxidase of the flavin-dependent disulfide reductase family from Methanocaldococcus jannaschii. 1911 48

Studies in both animals and humans indicate that angiogenesis is implicated in the development of atherosclerotic lesions. Thus, inhibition of angiogenesis may provide a novel therapeutic approach for the treatment of atherosclerosis. Because epidemiological studies have indicated an inverse relation between red wine intake and coronary disease, we determined the antiangiogenic potential of red wine polyphenols (RWPs) in the ischemic hindlimb model. Neovascularization was accelerated by the chronic infusion of angiotensin II (Ang II; 0.1 mg/kg/day). RWPs (25 mg/kg/day) or vehicle were administrated in the drinking water 7 days before the ligation. After 21 days, Ang II potentiated the ischemia-induced neovascularization in the hindlimb, as assessed by microangiography and measurement of microvessel density. This effect was associated with an increased formation of reactive oxygen species (ROS) and increased expression of hypoxia-inducible factor (HIF)-2alpha, endothelial nitric-oxide synthase (eNOS), and vascular endothelial growth factor (VEGF). RWPs intake significantly prevented the angiogenic process, the formation of ROS and nitrated proteins, and the expression HIF-2alpha, eNOS, and VEGF induced by Ang II. Similar preventive effects were observed with the antioxidant and NADPH oxidase inhibitor apocynin. These findings indicate that RWPs have potent antiangiogenic properties in vivo by preventing the expression of proangiogenic factors, including VEGF and eNOS most likely by inhibiting oxidative stress. Thus, the antiangiogenic properties of red wine polyphenols might contribute to their protective effect against coronary disease.
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PMID:Red wine polyphenols prevent acceleration of neovascularization by angiotensin II in the ischemic rat hindlimb. 1919 29

1. Oxidative stress contributes to endothelial dysfunction and atherogenesis in diabetes. The present study tested the hypothesis that a high-cholesterol diet accelerates endothelial dysfunction in Ins2(Akita) mice, a Type 1 diabetic model with a spontaneous autosomal preproinsulin gene (Ins2 gene) mutation, through further increase of superoxide production. 2. The Ins2(Akita) diabetic mice were fed a high-cholesterol diet (1.25% cholesterol) for 4 months. Some Ins2(Akita) mice were also treated for 4 months with the selective NADPH oxidase inhibitor apocynin (4 mg/kg per day in drinking water). Oxidative stress markers, tetrahydrobiopterin (BH4) levels, GTP cyclohydrolase I activity and endothelial function were determined in serum or arteries afterwards. 3. Serum lipid peroxidation and arterial superoxide levels were increased, whereas arterial BH(4) levels and GTP cyclohydrolase I activity were decreased, in Ins2(Akita) mice on a high-cholesterol diet, resulting in impaired endothelium-dependent nitric oxide-mediated relaxation in response to acetylcholine. 4. In vivo treatment with apocynin not only blunted serum lipid peroxidation and arterial superoxide levels, but also increased BH4 levels and GTP cyclohydrolase I activity, resulting in improved endothelium-dependent relaxation. 5. These results suggest that NADPH oxidase may play a potential role in oxidative stress-induced arterial BH4 and GTP cyclohydrolase I deficiency, resulting in endothelial dysfunction in Ins2(Akita) Type 1 diabetic mice fed a high-cholesterol diet.
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PMID:High-cholesterol diet augments endothelial dysfunction via elevated oxidative stress and reduced tetrahydrobiopterin in Ins2(Akita) mice, an autosomal dominant mutant type 1 diabetic model. 1920 18

Damage to nuclear DNA in human peripheral blood mononuclear cells was studied after in vitro treatment with bacterial endotoxin by alkaline comet assay. It was found that LPS induced DNA damage as soon as over the first 30 min of incubation, while by the 4th hour of incubation DNA damage was found in more than 95% cells. Exogenous superoxide dismutase completely protected DNA, which suggests that superoxide radical is the primary extracellular damaging agent. Polyphenol antioxidant (water-soluble lignin) and specific NADPH oxidase inhibitor (diphenyleneiodonium chloride) also produced a protective effect. Our results show that LPS-activated mononuclear cells can be used ex vivo as a convenient and adequate experimental system for evaluation of the efficiency of various substances in protection of lymphocyte DNA from the damaging effect of reactive oxygen species of LPS-stimulated monocytes.
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PMID:DNA damage in human mononuclear cells induced by bacterial endotoxin. 1924 Aug 45

Arsenic in drinking water is a major public health concern as it increases risk and incidence of cardiovascular disease and cancer. Arsenic exposure affects multiple vascular beds, promoting liver sinusoidal capillarization and portal hypertension, ischemic heart disease, peripheral vascular disease, and tumor angiogenesis. While Rac1-GTPase and NADPH oxidase activities are essential for arsenic-stimulated endothelial cell signaling for angiogenesis or liver sinusoid capillarization, the mechanism for initiating these effects is unknown. We found that arsenic-stimulated cell signaling and angiogenic gene expression in human microvascular endothelial cells were Pertussis toxin sensitive, indicating a G-protein coupled signaling pathway. Incubating human microvascular endothelial cells with the sphingosine-1-phosphate type 1 receptor (S1P(1)) inhibitor VPC23019 or performing small interfering RNA knockdown of S1P(1) blocked arsenic-stimulated HMVEC angiogenic gene expression and tube formation, but did not affect induction of either HMOX1 or IL8. Liver sinusoidal endothelial cells (LSECs) defenestrate and capillarize in response to aging and environmental oxidant stresses. We found that S1P(1) was enriched on LSECs in vivo and in primary cell culture and that VPC23019 inhibited both sphingosine-1-phosphate-stimulated and arsenic-stimulated LSEC oxidant generation and defenestration. These studies identified novel roles for S1P(1) in mediating arsenic stimulation of both angiogenesis and pathogenic LSEC capillarization, as well as demonstrating a role for S1P(1) in mediating environmental responses in the liver vasculature, providing possible mechanistic insight into arsenic-induced vascular pathogenesis and disease.
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PMID:Arsenic requires sphingosine-1-phosphate type 1 receptors to induce angiogenic genes and endothelial cell remodeling. 1934 68

Hyperoxaluria and crystal deposition induce oxidative stress (OS) and renal epithelial cells injury, both mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are considered as the main sources of reactive oxygen species (ROS). Taurine is known to have antioxidant activity and shows renoprotective effect. We investigate the effect of taurine treatment on renal protection, and the putative source of ROS, in a rat model of calcium oxalate nephrolithiasis. Rats were administered with 2.5% (V/V) ethylene glycol + 2.5% (W/V) ammonium chloride (4 ml/day), with restriction on intake of drinking water (20 ml/day) for 4 weeks. Simultaneous treatment with taurine (2% W/W, mixed with the chow) was performed. At the end of the study, indexes of OS and renal injury were assessed. Renal tubular ultrastructure changes were analyzed under transmission electron microscopy. Crystal deposition in kidney was scored under light microscopy. Angiotensin II in kidney homogenates was determined by radioimmunoassay. Expression of NADPH oxidase subunits p47phox and Nox-4 mRNAs in kidney was evaluated by real time-polymerase chain reaction. The data showed that oxidative injury of the kidney occurred in nephrolithiasis-induced rats. Hyperplasia of mitochondria developed in renal tubular epithelium. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondria decreased and the mitochondrial membrane showed oxidative injury. Taurine treatment alleviated the oxidative injury of the kidney, improved SOD and GSH-Px activities, as well as the mitochondrial membrane injury, with lesser crystal depositions in the kidney. We could not detect statistical changes in the renal angiotensin II level, and the renal p47phox and Nox-4 mRNAs expression in those rats. The results suggest that mitochondria but not NADPH oxidase may account for the OS and taurine protected kidney from oxidative injury through mitochondrial-linked pathway in this rat model.
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PMID:Taurine protected kidney from oxidative injury through mitochondrial-linked pathway in a rat model of nephrolithiasis. 1951 7

Using in vitro systems, numerous authors have cited the sensitivity of pollen tube growth to high temperature as a major cause of low yields for crops with valuable reproductive structures. We investigated the hypothesis that in vivo fertilization efficiency would be negatively affected by heat stress-induced changes in energy reserves and calcium-mediated oxidative status in the pistil. Gossypium hirsutum plants exposed to optimal (30/20 degrees C) or high day temperature (38/20 degrees C) conditions during flowering were analyzed for fertilization efficiency via UV microscopic observation of pollen tube-containing ovules and for soluble carbohydrates, adenosine triphosphate (ATP), calcium, antioxidant enzyme activity and NADPH oxidase (NOX; EC 1.6.3.1) activity in the pistil. Leaf measurements included gas exchange, chlorophyll content, quantum efficiency and ATP content of the subtending leaf on the day of anthesis. In the pistil fertilization efficiency, soluble carbohydrates, ATP content and NOX activity declined significantly, whereas water soluble calcium and glutathione reductase (EC 1.8.1.7) activity increased, and superoxide dismutase (EC 1.15.1.1) activity remained unchanged. In leaves, heat stress decreased photosynthesis, quantum efficiency and chlorophyll content, but increased stomatal conductance. We conclude that decreased source leaf activity either inhibits pollen development, tube growth through the style or guidance to the ovules as a result of an insufficient energy supply to the developing pistil. We further conclude that a calcium-augmented antioxidant response in heat-stressed pistils interferes with enzymatic superoxide production needed for normal pollen tube growth and fertilization of the ovule.
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PMID:Heat stress-induced limitations to reproductive success in Gossypium hirsutum. 1965 31

Molecular hydrogen ameliorates oxidative stress-associated diseases in animal models. We found that oral intake of hydrogen-rich water abolishes an immediate-type allergic reaction in mice. Using rat RBL-2H3 mast cells, we demonstrated that hydrogen attenuates phosphorylation of the FcepsilonRI-associated Lyn and its downstream signal transduction, which subsequently inhibits the NADPH oxidase activity and reduces the generation of hydrogen peroxide. We also found that inhibition of NADPH oxidase attenuates phosphorylation of Lyn in mast cells, indicating the presence of a feed-forward loop that potentiates the allergic responses. Hydrogen accordingly inhibits all tested signaling molecule(s) in the loop. Hydrogen effects have been solely ascribed to exclusive removal of hydroxyl radical. In the immediate-type allergic reaction, hydrogen exerts its beneficial effect not by its radical scavenging activity but by modulating a specific signaling pathway. Effects of hydrogen in other diseases are possibly mediated by modulation of yet unidentified signaling pathways. Our studies also suggest that hydrogen is a gaseous signaling molecule like nitric oxide.
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PMID:Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells. 1976 97

The renin-angiotensin system exerts a tremendous influence over fluid balance and arterial pressure. Angiotensin II (Ang-II), the effector peptide of the renin-angiotensin system, acts in the central nervous system to regulate neurohumoral outflow and thirst. Dysregulation of Ang-II signaling in the central nervous system is implicated in cardiovascular diseases; however, the mechanisms remain poorly understood. Recently we established that NADPH oxidase (Nox)-derived superoxide acting in the forebrain subfornical organ is critical in the physiological responses to central Ang-II. In addition, we have found that Nox2 and Nox4 are the most abundantly expressed Nox homologues within Ang-II-sensitive sites in the forebrain. To dissect out the functional importance and unique roles of these Nox enzymes in the pressor and dipsogenic effects of central Ang-II, we developed adenoviral vectors expressing small interfering RNA to selectively silence Nox2 or Nox4 expression in the subfornical organ. Our results demonstrate that both Nox2 and Nox4 are required for the full vasopressor effects of brain Ang-II but that only Nox2 is coupled to the Ang-II-induced water intake response. These studies establish the importance of both Nox2- and Nox4-containing NADPH oxidases in the actions of Ang-II in the central nervous system and are the first to reveal differential involvement of these Nox enzymes in the various physiological effects of central Ang-II.
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PMID:Genetic silencing of Nox2 and Nox4 reveals differential roles of these NADPH oxidase homologues in the vasopressor and dipsogenic effects of brain angiotensin II. 1980 37


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