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

---

Query: EC:1.6.3.1 (NADPH oxidase)
11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anionic amphiphiles have been shown to influence the NADPH oxidase system. Although one target of the amphiphile action is p47(phox), the cell-free activation of the enzyme in the absence of p47(phox) is also influenced. In the present study, we examined the actions of sodium dodecyl sulfate (SDS) on the NADPH oxidase system in vivo. Treatment of guinea pig neutrophils with the amphiphile caused the translocation of Rac to a membrane fraction and its conversion to the GTP-bound form. Because SDS had little effect on p47(phox), it increased the superoxide production only when p47(phox) was otherwise activated. Inhibitors of phosphoinositide 3-kinases had no effect on the SDS-induced translocation of Rac to the membrane. However, the inhibitors prevented the conversion of Rac to its GTP-bound form, indicating that these two processes can be controlled separately. In a cell-free system, SDS induced the binding of p47(phox) and Rac to the membrane preparation. The SDS concentration inducing the Rac binding was lower than that inducing the p47(phox) binding. Thus we observed that Rac is more sensitive to SDS than p47(phox) both in vivo and in vitro. The results suggest a role of natural amphiphiles such as unsaturated fatty acids in regulation of Rac activation.
...
PMID:The effect of anionic amphiphiles on the recruitment of Rac in neutrophils. 1562 15

We report a novel effect of dehydroepiandrosterone (DHEA) on human granulocyte differentiation: DHEA enhances the all-trans-retinoic acid (ATRA)-induced differentiation of promyelocytic NB4 cells. DHEA (100 microM) significantly augmented the respiratory burst activity of NB4 cells treated with 1 nM ATRA, whereas DHEA alone did not induce respiratory burst activity. The protein and message expressions of p67phox, the gene for the dose-limiting component of phagocyte NADPH oxidase, were significantly enhanced by the coexistence of DHEA and ATRA. The protein expression of p47phox, another component of phagocyte NADPH oxidase, was also up-regulated by DHEA and ATRA. Moreover, the ATRA-induced increment of CCAAT/enhancer-binding protein beta (C/EBPbeta) and the reciprocal reduction in C/EBPUalpha expression were also potentiated by DHEA. In contrast, the expression of PU.1, a transcription factor reportedly involved in the basal expression of p67phox in monocytic cells, was only slightly up-regulated by DHEA and ATRA. Interestingly, DHEA sulfate (DHEAS), the sulfate ester of DHEA that exists in peripheral blood at a concentration approximately 3 orders of magnitude larger than that of DHEA, did not stimulate the ATRA-induced differentiation of NB4 cells. Thus, DHEA, but not DHEAS, plays important roles in synergy with ATRA during granulocyte differentiation of human promyelocytic NB4 cells.
...
PMID:Synergistic effects of dehydroepiandrosterone and retinoic acid on granulocytic differentiation of human promyelocytic NB4 cells. 1571 86

Human inflammatory bowel diseases (IBD) are associated with significant alterations in intestinal blood flow, the direction and magnitude of which change with disease progression. The objectives of this study were to determine the time course of changes in colonic blood perfusion that occur during the development of dextran-sodium-sulfate (DSS)-induced colonic inflammation and to address the mechanisms that may underlie these changes in blood flow. Intravital microscopy was used to quantify blood flow (from measurements of vessel diameter and red blood cell velocity) in different-sized submucosal arterioles of control and inflamed colons in wild-type (WT) mice. A significant (18-30%) reduction in blood flow was noted in the smallest arterioles (<40 microm diameter) on days 4-6 of DSS colitis. The arteriolar responses to bradykinin in control and DSS-treated WT mice revealed an impaired endothelium-dependent, but not endothelium-independent, vasodilation in the inflamed colon. However, this impaired vasodilatory response to bradykinin after DSS treatment was not evident in mutant mice that overexpress Cu,Zn-superoxide dismutase. Rescue of the bradykinin-induced vasodilation during DSS colitis was also observed in mice that are genetically deficient in the NAD(P)H oxidase subunit gp91(phox). These findings indicate that the decline in blood flow during experimental colitis may result from a diminished capacity of colonic arterioles to respond to endogenous endothelium-dependent vasodilators like bradykinin and that NAD(P)H oxidase-derived superoxide plays a major role in the induction of the inflammation-induced endothelium-dependent arteriolar dysfunction.
...
PMID:Colonic blood flow responses in experimental colitis: time course and underlying mechanisms. 1608 59

Indoxyl sulfate is a protein metabolite that is concentrated in the serum of patients with chronic renal insufficiency. It also is a uremic toxin that has been implicated in the progression of chronic renal disease in rodent models. We have shown previously that mesangial cell redox status is related to activation of mitogen-activated protein kinases and cell proliferation, which are factors related to glomerular damage. We used three methods to examine the ability of indoxyl sulfate to alter mesangial cell redox as a possible mechanism for its toxicity. Indoxyl sulfate increases mesangial cell reduction rate in a concentration-dependent manner as demonstrated by redox microphysiometry. Alterations occurred at concentrations as low as 100 microM, with more marked alterations occurring at higher concentrations associated with human renal failure. We demonstrated that indoxyl sulfate induces the production of intracellular reactive oxygen species (ROS) in mesangial cells (EC50 = 550 microM) by using the ROS-sensitive fluorescent dye CM-DCF. ROS generation was only partially (approximately 50%) inhibited by the NADPH oxidase inhibitor diphenylene iodinium at low (< or = 300 microM) indoxyl sulfate concentrations. Diphenylene iodinium was without effect at higher concentrations of indoxyl sulfate. We also used electron paramagnetic spin resonance spectroscopy with extracellular and intracellular spin traps to show that indoxyl sulfate increases extracellular SOD-sensitive O2-* production and intracellular hydroxyl radical production that may derive from an initial O2-* burst. These results document that indoxyl sulfate, when applied to renal mesangial cells at pathological concentrations, induces rapid and complex changes in mesangial cell redox.
...
PMID:Indoxyl sulfate induces complex redox alterations in mesangial cells. 1643 74

Gut-derived, endotoxin-mediated hepatocellular damage has been postulated to play a crucial role in the pathogenesis of alcohol-induced liver injury in rodents. Endotoxins induce production of tumor necrosis factor alpha (TNF-alpha) by Kupffer cells via Toll-like receptor (TLR) 4 and contribute to liver injury. This study addressed the contribution of other TLRs and ligands to alcoholic fatty liver. C57Bl6/J mice were fed a modified Lieber-DeCarli diet. Serum aminotransferase measurements, histological analysis, and quantification of liver TNF-alpha and TLR1-9 messenger RNA (mRNA) were performed. The effect of TLR ligands on liver injury was assessed in vivo. Neomycin and metronidazole or diphenyleneiodonium sulfate (DPI) were administered to evaluate the role of gut bacteria and NADPH oxidase activity, respectively, in hepatic TLR expression. Enteral ethanol (EtOH) exposure induced steatosis and increased liver weight, aminotransferase levels, and expression of TLR1, 2, 4, 6, 7, 8, and 9 liver mRNA. Injection of lipoteichoic acid, peptidoglycan (PGN), lipopolysaccharide (LPS), loxoribine, and oligonudeotide containing CpG (ISS-ODN) increased TNF-alpha mRNA expression more in the livers of EtOH-fed mice than in control mice. PGN, LPS, flagellin, and ISS-ODN induced liver inflammatory infiltrate in EtOH-fed mice but not control mice. Addition of antibiotics reduced the severity of alcoholic fatty liver without affecting TLR expression, whereas daily DPI injections reduced the EtOH-mediated upregulation of TLR2, 4, 6, and 9 mRNA. In conclusion, EtOH-fed mice exhibited an oxidative stress dependent on upregulation of multiple TLRs in the liver and are sensitive to liver inflammation induced by multiple bacterial products recognized by TLRs.
...
PMID:Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver. 1662 28

Oxidative stress may be an important determinant of the severity of acute pancreatitis. One-electron reduction of oxidants generates reactive oxygen species (ROS) via redox cycling, whereas two-electron detoxification, e.g. by NAD(P)H:quinone oxidoreductase, does not. The actions of menadione on ROS production and cell fate were compared with those of a non-cycling analogue (2,4-dimethoxy-2-methylnaphthalene (DMN)) using real-time confocal microscopy of isolated perfused murine pancreatic acinar cells. Menadione generated ROS with a concomitant decrease of NAD(P)H, consistent with redox cycling. The elevation of ROS was prevented by the antioxidant N-acetyl-l-cysteine but not by the NADPH oxidase inhibitor diphenyliodonium. DMN produced no change in reactive oxygen species per se but significantly potentiated menadione-induced effects, probably via enhancement of one-electron reduction, since DMN was found to inhibit NAD(P)H:quinone oxidoreductase detoxification. Menadione caused apoptosis of pancreatic acinar cells that was significantly potentiated by DMN, whereas DMN alone had no effect. Furthermore, bile acid (taurolithocholic acid 3-sulfate)-induced caspase activation was also greatly increased by DMN, whereas DMN had no effect per se. These results suggest that acute generation of ROS by menadione occurs via redox cycling, the net effect of which is induction of apoptotic pancreatic acinar cell death. Two-electron detoxifying enzymes such as NAD(P)H:quinone oxidoreductase, which are elevated in pancreatitis, may provide protection against excessive ROS and exert an important role in determining acinar cell fate.
...
PMID:Menadione-induced reactive oxygen species generation via redox cycling promotes apoptosis of murine pancreatic acinar cells. 1708 48

The mechanisms of cell injury resulting in a special type of cell death combining the features of apoptosis and necrosis were examined in Hep-2 cells exposed to 300 microM zinc sulfate during 24 h. Acute exposure to zinc induced a rapid rise in metallothionein levels and increased oxidative stress occurring in the absence of a significant early ATP depletion. Accentuated ATP loss and elevated levels of superoxide at later treatment intervals (12 h and longer) were present along with increased DNA damage. Manipulation with ATP production and inhibition of NADPH oxidase had a positive effect on zinc-related increase in oxidative stress and influenced the observed type of cell death. These results suggest that Hep-2 cells acutely exposed to zinc increase intracellular labile zinc stores and over express metalothioneins. Elevated production of peroxides in zinc-treated cells is at later treatment intervals accompanied by an increase in superoxide levels, possibly by activation of NADPH oxidase, DNA damage and severe ATP loss. Prevention of critical ATP depletion and, in particular, inhibition of oxidative stress attenuates zinc-mediated cell injury and stimulates apoptosis-like phenotype in exposed cells.
...
PMID:Depletion of ATP and oxidative stress underlie zinc-induced cell injury. 1765 35

We previously showed that ANG II induces mesangial cell (MC) proliferation via the JNK-activator protein-1 pathway. The present study attempted to determine the upstream mediators of JNK activation, with emphasis on reactive oxygen species (ROS) and the epidermal growth factor (EGF) receptor (EGFR). In cultured human MCs (HMCs), as early as 3 min, ANG II time dependently increased intracellular ROS production, which was sensitive to 10 microM diphenyleneiodonium sulfate and 500 microM apocynin, two structurally distinct NADPH oxidase inhibitors. In contrast, inhibitors of other oxidant-producing enzymes, including the mitochondrial complex I inhibitor rotenone, the xanthine oxidase inhibitor allopurinol, the cyclooxygenase inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguiaretic acid, the cytochrome P-450 oxygenase inhibitor ketoconazole, and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester, were without effect. ANG II-induced ROS generation was inhibited by the angiotensin type 1 receptor antagonist losartan (10 muM) but not the angiotensin type 2 receptor antagonist PD-123319 (10 microM). ANG II induced translocation of p47(phox) and p67(phox) from the cytosol to the membrane. The antioxidants almost abolished the ANG II mitogenic response, as assessed by [(3)H]thymidine incorporation and cell number, associated with a remarkable blockade of the activation of EGFR (90% inhibition) and JNK (83% inhibition). The EGFR inhibitor AG-1478 was able to mimic the effect of antioxidants, in that it inhibited the mitogenic response and the JNK activation following ANG II treatment. Together, these data suggest that the ROS-EGFR-JNK pathway is involved in transducing the proliferative effect of ANG II in cultured HMCs.
...
PMID:ANG II induces c-Jun NH2-terminal kinase activation and proliferation of human mesangial cells via redox-sensitive transactivation of the EGFR. 1788 65

Epidemiological studies have reported an inverse association between dietary flavonoid intake and mortality for ischemic heart disease. Quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, but it is rapidly metabolized during absorption by methylation, glucuronidation and sulfation. We have analyzed the vasorelaxant effects and the role on NO bioavailability and endothelial function of quercetin and its conjugated metabolites (quercetin-3-glucuronide, isorhamnetin-3-glucuronide and quercetin-3'-sulfate) in rat aorta. Thoracic aortic rings isolated from Wistar rats were mounted for isometric force recording and endothelial function was tested by measuring the vasorelaxant response to acetylcholine. NADPH-enhanced O(2)(-) release was quantified in homogenates from cultured aortic smooth muscle cells using lucigenin chemiluminescence. Unlike quercetin, the conjugated metabolites had no direct vasorelaxant effect, and did not modify endothelial function or the biological activity of NO. However, all metabolites (at 10 micromol/L) prevented, at least partially, the impairment of endothelial-derived NO response under conditions of high oxidative stress induced by the SOD inhibitor DETCA. Furthermore, they protected the biological activity of exogenous NO when impaired by DETCA. Quercetin and quercetin-3'-sulfate (>or=10 micromol/L) or quercetin-3-glucuronide (100 micromol/L) inhibited NADPH oxidase-derived O(2)(-) release. Quercetin and quercetin-3-glucuronide (1 micromol/L) prevented the endothelial dysfunction induced by incubation with ET-1. These data indicate, for the first time, that the conjugated metabolites could be responsible for the in vivo protective activity of quercetin on endothelial dysfunction.
...
PMID:Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta. 1880 86

Patients with chronic renal failure are at greater risk of developing atherosclerosis than healthy individuals, and recent data suggest that the putative uremic toxin indoxyl sulfate (IS) promotes the pathogenesis of atherosclerosis. The present study examined the effects of IS on vascular smooth muscle cells (VSMCs) with respect to reactive oxygen species (ROS), platelet-derived growth factor (PDGF) receptors, and mitogen-activated protein kinases (MAPKs). IS induced the migration and proliferation of VSMCs and synergistically enhanced their PDGF-induced migration as well as proliferation. The effects of PDGF were promoted after a 24-h incubation with IS despite the absence of IS during PDGF stimulation. Intracellular ROS levels were increased in the presence of IS, and PDGF-dependent ROS production was augmented by a prior 24-h incubation with IS even in the absence of IS during PDGF stimulation. These data suggest that IS increases the sensitivity of VSMCs to PDGF. IS also phosphorylated PDGF-beta-receptors and upregulated PDGF-beta receptor but not alpha-receptor protein expression in the absence of exogenous PDGF. The NADPH oxidase inhibitor diphenylene iodonium blocked IS-dependent increase in receptor expression. Administration of IS to nephrectomized rats also elevated receptor protein expression in arterial VSMCs. Inhibitors of NADPH oxidase, PDGF-beta receptors, extracellular-regulated protein kinase (ERK), and p38 MAPK all inhibited IS-induced VSMCs migration and proliferation. Taken together, these findings indicate that IS induces the migration as well as proliferation of VSMCs through PDGF-beta receptors and that ROS generation is critically involved in this process, which promotes the development of atherosclerosis.
...
PMID:ROS and PDGF-beta [corrected] receptors are critically involved in indoxyl sulfate actions that promote vascular smooth muscle cell proliferation and migration. 1949 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---