Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the generation of superoxide and hydrogen peroxide by NADPH oxidase and nitric oxide (NO) by NO synthase (NOS) in granulocytes is NADPH-dependent, we investigated the production of NO, superoxide and H2O2 in glucose 6-phosphate dehydrogenase (G6PD)-deficient human granulocytes. Our results showed that upon stimulation with either 5 microg/ml of lipopolysaccharide (LPS) or 10 microM of phorbol 12-myristate 13-acetate (PMA), the production of nitrite in normal granulocytes was elevated, 252 +/- 135% and 239 +/- 72%, respectively, compared to the resting stage. In contrast, G6PD-deficient granulocytes did not produce more nitrite upon stimulation with either LPS or PMA compared to the resting stage. Western blot analysis indicated a normal expression pattern of inducible NOS in G6PD-deficient granulocytes. In addition, the production of H2O2 and superoxide was also significantly impaired in G6PD-deficient granulocytes compared to control cells. These data demonstrate that G6PD deficiency causes an impairment in the production of NO, superoxide and H2O2.
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PMID:Impaired production of nitric oxide, superoxide, and hydrogen peroxide in glucose 6-phosphate-dehydrogenase-deficient granulocytes. 980 Nov 59

Treatment of rat aortic smooth muscle cells (RASMC) with 1 or 100 microg ml-1 lipopolysaccharide (LPS) for 20-24 h led to expression of the inducible form of nitric oxide synthase (iNOS) as detected by Western blotting for iNOS protein, and by determination of increased cellular nitrite formation. LPS-induced nitrite production was inhibited almost completely by concomitant treatment of cells with LPS and either (a) pyrrolidine dithiocarbamate (PDTC, 25 microm), an antioxidant inhibitor of NF-kappaB activation; (b) N-tosyl-L-phenylalanine chloromethyl ketone (TPCK, 20 and 40 microm), a proteasomal inhibitor which prevents NF-kappaB activation; (c) nordihydroguaiaretic acid (NDGA, 10 and 50 microm), a lipoxygenase inhibitor; or (d) apocynin (2, 3.5 and 5 m m), an inhibitor of NADPH oxidase. Gel-shift assays using nuclear protein extracts incubated with a 32P-labelled DNA binding probe for NF-kappaB detected two electrophoretically separable complexes containing NF-kappaB. A faster migrating complex obtained when using both LPS-treated and untreated cells appeared to represent a basal or constitutive NF-kappaB activity, whereas a slower band was found only after LPS-treatment. The latter band was abolished when using cells treated for 1 h with LPS in the presence of PDTC (25 microm) or TPCK (20 microm), but was not inhibited by NDGA (50 microm) or apocynin (3.5 m m). The basal band was unaffected by any of the cell signalling inhibitors. Densitometry of Western blots indicated that LPS-induced iNOS protein expression was inhibited to a similar extent (between 74 and 87%) by the latter concentrations of PDTC, TPCK, NDGA and apocynin. The ability of PDTC and TPCK to abolish LPS-specific NF-kappaB activation, while also producing considerable inhibition of iNOS protein expression and nitrite formation, suggests that induction of iNOS by LPS in RASMC involves NF-kappaB-dependent transcription. However, the failure of NDGA and apocynin to prevent NF-kappaB activation, at least during early stages (up to 1 h) of its nuclear accumulation, suggests that these agents may affect cell signalling pathways which regulate iNOS induction by another mechanism to be determined.
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PMID:Differential effects of some cell signalling inhibitors upon nitric oxide synthase expression and nuclear factor-kappaB activation induced by lipopolysaccharide in rat aortic smooth muscle cells. 1032 94

Recently, we showed that cultured guinea pig gastric pit cells possess a phagocyte NADPH oxidase-like activity, which was up-regulated by Helicobacter pylori lipopolysaccharide. We demonstrate here that these cells express all of the phagocyte NADPH oxidase components (gp91-, p22-, p67-, p47-, and p40-phoxes). Treatment with lipopolysaccharide increased the expression of gp91-, p22-, and p67-phoxes, but not that of p47- and p40-phoxes. Intriguingly, the p67-phox expression consistently correlated with up-regulation of superoxide anion-producing ability. Thus, the gastric pit cell NADPH oxidase may play an important role in regulation of the inflammatory response associated with H. pylori infection.
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PMID:Helicobacter pylori lipopolysaccharide enhances the expression of NADPH oxidase components in cultured guinea pig gastric mucosal cells. 1038 99

It has been suggested the the interaction of Escherichia coli O157-derived verotoxins (VTs) with the vascular endothelium plays a central role in the pathogenesis of the thrombotic microangiopathy and ischemic lesions characteristic of hemolytic uremic syndrome (HUS) and E. coli O157-associated hemorrhagic colitis. Intravenous administration of both E. coli O157-derived VT1 and lipopolysaccharide (LPS) in the rat induced a synergistic increase in thiobarbituric acid (TBA) values in those animal's plasma, as compared with that injected with VT1 or LPS alone. We then hypothesized that an increase in lipid peroxidation in the rat plasma was due to an enhanced production of endothelial cell-derived reactive oxidant. Based on determination of rat sera and cultured human aortic endothelial cells (HAECs), VT1 had little if any effect on LPS-stimulated increase of nitric oxide and the resultant peroxynitrite generations. Both RT-PCR and Western blot studies of reactive oxygen species-related enzymes showed that VT1 markedly decreased the expression of catalase mRNA and protein in HAECs, but caused less alteration in the levels of Cu, Zn-superoxide dismutase, and NADPH oxidase mRNA. Further studies by spin trapping analysis using 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) revealed a time-dependent increase in hydroxyl radicals by VT1 in HAECs. The accumulated data thus suggest that bacterial VT1 reduces mainly catalase levels in endothelial cells, which is synergistically potentiated by LPS, and that the resulting hydroxyl radical participates in endothelium injury through a marked enhancement of lipid peroxidation, leading to HUS.
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PMID:Reactive oxygen species as a risk factor in verotoxin-1-exposed rats. 1040 47

Stress response is mediated by a number of stress-related gene products and is crucial for maintenance of homeostasis during and after various cellular stresses. Exposure of rats to restraint and water-immersion stress rapidly and transiently activated heart shock factor 1 (HSF1) and caused rapid HSP70 mRNA expression and HSP70 accumulation in gastric mucosa. Using protein-malnourished, bilateral adrenalectomized, and subdiaphragmatically vagotomized rats, we showed that this heat shock response was regulated by the hypothalamic-pituitary-adrenocortical or the sympathoadrenal systems. Experiments with inhibitors for adrenoceptor subtypes and glucocorticoids suggested that the alpha 1A-adrenergic receptor appeared to mediate the HSP70 induction. The extent of HSP70 induction inversely correlated to the severity of mucosal damage, suggesting an important role of the heat shock response in gastric mucosal defense under conditions of stress. Recently, we found that gastric surface mucous cells possessed a phagocyte NADPH oxidase-like system and secreted abundant superoxide anion (O2.-). Helicobactor pylori lipopolysaccharide markedly up-regulated this secretion. The enhanced O2.- production activated nuclear factor kappa B by autocrine/paracrine mechanisms, resulting in activation of proinflammatory cytokine gene expressions. These results suggest that surface mucous cells may actively regulate stress responses of Helicobacter pylori-infected gastric mucosa through a phagocyte NADPH oxidase-like activity.
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PMID:[Molecular stress response in the stomach]. 1062 39

Since carvedilol has been claimed to possess antioxidative effects, this drug might affect functional responses, including nitric oxide (NO) generation, of polymorphonuclear neutrophils (PMN) and macrophages. When we assessed the effects of carvedilol on PMN responses in vitro, we observed that carvedilol dose dependently modulated generation of superoxide ions by NADPH oxidase when induced by the formylpeptide formyl-methionyl-leucyl-phenylalanine (fMLP) or the phorbol ester phorbol myristate acetate. This effect was not coupled to diminished phospholipase C activity. In contrast to the effect on NADPH oxidase, neither the fMLP-elicited NO generation by PMN nor the response of the murine macrophage cell line J774 to lipopolysaccharide was affected. There was no evidence from cell-free assay systems that carvedilol is a scavenger for superoxide ions or NO. Moreover, carvedilol did not affect other reactions dependent on NO, e.g. spontaneous or fMLP-stimulated PMN migration or lipoxin A(4)-, fMLP-, or A23187-induced neutrophil cytotoxicity for human umbilical vein endothelial cells. Thus, these effects point to the possibility that carvedilol modulates the NADPH oxidase of PMN but leaves the nitric oxide synthase of phagocytes intact.
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PMID:No effect of carvedilol on nitric oxide generation in phagocytes but modulation of production of superoxide ions. 1069 66

Radical-scavenging antioxidants, as part of the cellular defense system, function to inhibit the formation and propagation of free radicals and active oxygen species formation. In previous studies we demonstrated that endotoxin lipopolysaccharide (LPS) promotes oxidative stress and associated pathological changes in a rat model and that use of selected antioxidants was effective in reducing LPS-related lipid peroxidation product formation in the liver, as well as LPS-related pathological changes in different organs. In this study, several toxicological parameters (ie, clinical signs, blood chemistry, and histopathological changes) were compared among groups of male New Zealand rabbits injected with LPS following prophylactic pretreatment with either of 2 antioxidants, a group injected with LPS without pretreatment with antioxidants, groups injected with either of the 2 antioxidants only, and an untreated control group. The antioxidants used were a water-soluble natural antioxidant (NAO) from spinach and the NADPH oxidase inhibitor, apocynin. Exposure to LPS alone was associated clinically with depression, tachypnea, outer ear vasodilation, and iris congestion; biochemically with a significant increase in blood total bilirubin, transaminase activity, and glucose, total cholesterol, and triglyceride levels; macroscopically with multiple whitish areas in the liver; and histologically with hepatocellular focal necrosis and acute inflammation, thymic and splenic lymphoid necrosis and depletion, acute uveitis and hemorrhages in the ciliary processes, and decreased adrenal cortical cytoplasmic vacuolation considered consistent with depletion of steroidal hormone contents. The NAO had more effective prophylactic capacities than the apocynin. The protective effects were obvious in all investigated parameters. The results indicate the possible therapeutic efficacy of NAO in the treatment of clinical endotoxemia associated with gram-negative bacterial sepsis that is known to be associated with oxidative stress.
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PMID:The prophylactic effects of natural water-soluble antioxidant from spinach and apocynin in a rabbit model of lipopolysaccharide-induced endotoxemia. 1093 47

Overproduction of nitric oxide (NO) or superoxide (O2-) by activated macrophages is known to be involved in acute or chronic inflammation. The seeds of Job's Tears (Coix lachryma-jobi L. var. ma-yuen) have been used as anti-inflammatory medicine and health food. However, it is still unclear how the seeds show anti-inflammatory properties. Using murine macrophage-like RAW 264.7 cells, we tried to know whether the overproduction of NO and O2 by activated macrophages could be prevented by the methanol (MeOH) extract of the seeds of Job's Tears. RAW 264.7 cells were activated with interferon-gamma plus lipopolysaccharide to produce NO and with pholbol ester to produce O2-. The MeOH extract showed marked inhibition of NO production by activated RAW 264.7 cells in a dose-dependent manner via suppression of inducible NO synthase mRNA expression. The MeOH extract also showed inhibition of O2- production by activated RAW 264.7 cells in dose- and time-dependent manners, possibly by interfering with NADPH oxidase machinery of macrophages. Collectively, these results demonstrate that the MeOH extract of the seeds of Job's Tears shows anti-inflammatory properties which may, in part, involve an inhibition of NO and O2- production by activated macrophages.
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PMID:Inhibitory effects of methanol extract of seeds of Job's Tears (Coix lachryma-jobi L. var. ma-yuen) on nitric oxide and superoxide production in RAW 264.7 macrophages. 1094 31

A role for free radicals has been proposed in infectious brain disease, where resident microglia cells upregulate the inducible nitric oxide synthase isoform (iNOS), and thus are capable of producing nitric oxide at enhanced rates. Using the constitutively expressed NADPH oxidase, microglial cells can generate superoxide, which reacts with nitric oxide to form the powerful oxidant peroxynitrite. In a mixed cell culture system of astrocytes and microglial cells, nitrite levels, used as an indicator of nitric oxide production, were elevated after the addition of lipopolysaccharide (LPS) and cytokines. Immunohistochemistry and the NADPH diaphorase technique demonstrated selective localization of the iNOS protein in microglial cells, whereas no iNOS protein or NADPH diaphorase activity was detected in astrocytes. A similar cellular distribution was observed in vivo following injection of LPS and cytokines into the rat striatum. By contrast, LPS and interferon-gamma led to translocation of NF-kappaB in microglia and in astrocytes, demonstrating that both cell types are responsive to the stimulus. Therefore, downstream control in iNOS expression is cell type-specific.
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PMID:Selective upregulation of inducible nitric oxide synthase (iNOS) by lipopolysaccharide (LPS) and cytokines in microglia: in vitro and in vivo studies. 1097 10

The respiratory burst of human neutrophils is primed by a number of pro-inflammatory stimuli, including tumor necrosis factor-alpha (TNFalpha) and lipopolysaccharide (LPS); however, the mechanism of priming remains unknown. LPS has been shown previously to increase membrane expression of flavocytochrome b(558), a component of the NADPH oxidase. This study shows that TNFalpha also increases membrane expression of flavocytochrome b(558). Mitogen-activated protein kinase (MAPK) modules have been implicated in the action of priming agents. Pharmacologic inhibitors of MAPKs, SB203580 and PD098059, revealed that priming of the respiratory burst and up-regulation of flavocytochrome b(558) are dependent on p38 MAPK but not on extracellular-signal regulated kinase (ERK). TNFalpha and LPS primed respiratory burst activity and increased membrane expression of CD35 and CD66b, specific markers of secretory vesicles and specific granules that contain flavocytochrome b(558), with similar time courses and concentration dependences. These processes also required p38 MAPK but were independent of ERK. TNFalpha failed to prime respiratory burst activity or to increase membrane CD35 expression in enucleated neutrophil cytoplasts. These data suggest that one mechanism by which TNFalpha and LPS prime neutrophil respiratory burst activity is by increasing membrane expression of flavocytochrome b(558) through exocytosis of intracellular granules in a process regulated by p38 MAPK.
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PMID:Priming of the neutrophil respiratory burst involves p38 mitogen-activated protein kinase-dependent exocytosis of flavocytochrome b558-containing granules. 1097 3


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