Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is shed in its soluble form by a disintegrin and metalloproteinase (ADAM) called TNF-alpha convertase (TACE; ADAM17). TNF-alpha plays a role in inflammatory bowel disease (IBD) and is involved in the expression of inducible nitric oxide synthase (iNOS) which has also been implicated in IBD. The study was designed to investigate whether colitis induced by trinitrobenzene sulphonic acid (TNBS) in rats produces an increase in TACE activity and/or expression and whether its pharmacological inhibition reduces TNF-alpha levels, iNOS expression and colonic damage in this model. TNBS (30 mg in 0.4 ml of 50% ethanol) was instilled into the colon of female Wistar rats. Saline or TACE inhibitor BB1101 (10 mg/kg/day) was administered intraperitoneally 5 days after TNBS instillation. On day 10, colons were removed and assessed for pathological score, myeloperoxidase (MPO), NO synthase (NOS), TACE enzymatic activity and protein levels, colonic TNF-alpha and NOx- levels. Instillation of TNBS caused an increase in TACE activity and expression and the release of TNF-alpha. TNBS also resulted in iNOS expression and colonic damage. BB1101 blocked TNBS-induced increase in TACE activity, TNF-alpha release and iNOS expression. Concomitantly, BB1101 ameliorated TNBS-induced colonic damage and inflammation. TNBS causes TNF-alpha release by an increase in TACE activity and expression and this results in the expression of iNOS and subsequent inflammation, suggesting that TACE inhibition may prove useful as a therapeutic means in IBD.
 ...
PMID:Implication of TNF-alpha convertase (TACE/ADAM17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis. 1188 25

We evaluated the effect of various PGE analogs specific to EP receptor subtypes on indomethacin-induced small intestinal lesions in rats and investigated the relationship of EP receptor subtype with the PGE action using EP receptor knockout mice. Animals were administered indomethacin subcutaneously, and they were killed 24 hr later. 16,16-dimethyl prostaglandin E2 (dmPGE2) or various EP agonists were administered intravenously 10 min before indomethacin. Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied with an increase in intestinal motility and the number of enteric bacteria as well as iNOS and MPO activities. Prior administration of dmPGE2 dose-dependently prevented intestinal lesions, together with inhibition of those functional changes. These effects of dmPGE2 were mimicked by prostanoids (ONO-NT-012 and ONO-AE1-329), only specific to EP3 or EP4 receptors, although the intestinal motility was inhibited only by ONO-AE1-329. Intestinal mucus secretion and fluid accumulation were decreased by indomethacin but enhanced by dmPGE2, ONO-NT-012, and ONO-AE1-329 at the doses that prevented intestinal lesions. Indomethacin also caused intestinal lesions in both wild-type and knockout mice lacking EP1 or EP3 receptors, yet the protective action of dmPGE2 was observed in wild-type and EP1 receptor knockout mice but not the mice lacking EP3 receptors. These results suggest that the intestinal cytoprotective action of PGE2 against indomethacin is mediated by EP3/EP4 receptors and that this effect is functionally associated with an increase of mucus secretion and enteropooling as well as inhibition of intestinal hypermotility, the former two processes mediated by both EP3 and EP4 receptors, and the latter by EP4 receptors.
 ...
PMID:16,16-Dimethyl prostaglandin E2 inhibits indomethacin-induced small intestinal lesions through EP3 and EP4 receptors. 1199 26

Oxidative stress plays an important role in the early stage of acute pancreatitis as well as the associated multiple organ injury. Here we compare the degree of pancreatitis caused by cerulein in mice lacking the inducible (or type 2) nitric oxide synthase (iNOS) and in the corresponding wild-type mice. Intraperitoneal injection of cerulein resulted in wild-type mice in a severe, acute pancreatitis, which was characterized by edema, neutrophil infiltration, tissue hemorrhage and cell necrosis as well as increases in the serum levels of amylase and/or lipase. The infiltration of the pancreatic tissue of these animals with neutrophils (measured as increase in myeloperoxidase activity) was associated with up-regulation/expression of the adhesion molecules ICAM-1 and P-selectin as well as signs of enhanced lipid peroxidation (e.g., increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for nitrotyrosine and poly (ADP-ribose) synthetase (PARS) in the pancreas of cerulein-treated iNOS wild-type mice. In contrast, the degree of pancreatic inflammation and tissue injury (histological score), upregulation/expression of P-selectin and ICAM-1, the staining for nitrotyrosine and PARS, and lipid peroxidation was markedly reduced in pancreatic tissue sections obtained from cerulein-treated iNOS-deficient mice. These findings support the view that iNOS plays an important, pro-inflammatory role in the acute pancreatitis caused by cerulein in mice.
 ...
PMID:Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein. 1202 64

Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a role in the development of asbestos-related pulmonary disorders. The pulmonary reactions of rats and hamsters upon exposure to asbestos fibers are well known to be disparate. In addition, in vitro experiments have indicated that mononuclear phagocytes from hamsters, in contrast to those from rats, lack the iNOS pathway. Therefore, the purpose of this study was to investigate whether rats and hamsters differ in lung iNOS expression in vivo upon exposure to asbestos fibers and whether differences in iNOS induction are associated with differences in the acute pulmonary inflammatory reaction. Body weight, alveolar-arterial oxygen difference, differential cell count in bronchoalveolar lavage fluid, total protein leakage, lung myeloperoxidase activity and lipidperoxidation, wet/dry ratio, iNOS mRNA and protein expression, and nitrotyrosine staining of lung tissue were determined 1 and 7 days after intratracheal instillation of asbestos fibers in CD rats and Syrian golden hamsters. Exposure of rats to asbestos fibers resulted in enhanced pulmonary iNOS expression and nitrotyrosine staining together with an acute inflammation that was characterized by an influx of neutrophils, enhanced myeloperoxidase activity and lipid peroxidation, damage of the alveolar-capillary membrane, edema formation, and impairment of gas exchange. In comparison, instillation of asbestos fibers in hamsters resulted in a significantly milder inflammatory reaction of the lung with no induction of iNOS in pulmonary cells. The data obtained provide important information to understand the underlying mechanisms of species differences in the pulmonary response upon exposure to asbestos fibers.
 ...
PMID:Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase. 1205 93

1: We have examined the relationship between neutrophil accumulation, NO(*) production and nitrated protein levels in zymosan-mediated inflammation in rat skin in vivo. 2: Rats were anaesthetized and cutaneous inflammation was induced by zymosan (injected intradermally, i.d.). Experiments were carried out up to 48 h, in recovery procedures as appropriate. Assays for neutrophil accumulation (measurement of myeloperoxidase), nitric oxide (assessment of NO(2)(-)/NO(3)(-)) and nitrated proteins (detected by ELISA and Western blot) were performed in skin extracts. 3: The results demonstrate a close temporal relationship between these parameters. Samples were assayed at 1, 4, 8, 24 and 48 h after i.d. injection of zymosan. The highest levels measured of each parameter (P<0.001 compared with vehicle) were found at 4-8 h, with a reduction towards basal levels by 24 h. 4: Selective depletion of circulating neutrophils with anti-neutrophil antibody abolished neutrophil accumulation and protein nitration. In addition substantially decreased NO levels were found. 5: A selective inducible nitric oxide synthase (iNOS) inhibitor, N-3-aminomethyl-benzyl-acetamidine-dihydrochloride (1400W) also significantly reduced neutrophil levels and NO production and substantially inhibited protein nitration. 6: We conclude that the neutrophil leukocyte plays an essential role in the formation of iNOS-derived NO and nitrated proteins in inflammation, in a time-dependent and reversible manner. The NO-derived iNOS also has a role in stimulating further neutrophil accumulation into skin. This suggests a close mechanistic coupling between neutrophils, NO production and protein nitration.
 ...
PMID:Protein nitration in cutaneous inflammation in the rat: essential role of inducible nitric oxide synthase and polymorphonuclear leukocytes. 1214 98

Peroxynitrite is assumed to play a crucial role in brain damage associated with the overproduction of nitric oxide (NO). The purpose of this study is to examine time-dependent changes of nitrite and nitrate (NOx) concentration in the circulation, and peroxynitrite formation as well as the expression of inducible nitric oxide synthase (iNOS) in the penumbra of rat brains during transient middle cerebral artery occlusion (MCAO) of Wistar rat for 2 h and reperfusion for 4-70 h. NOx concentration in the circulation was continuously monitored at the right jugular vein by microdialysis. The expression of iNOS was detected at 22-70 h after reperfusion in vascular walls and the cortex. Nitrotyrosine, a marker of peroxynitrite, appeared 4 h after reperfusion in the cortex, increasing substantially at 22-46 h in vascular walls. NOx level in dialysate increased immediately after MCAO. After a gradual decrease, the level increased again 4 h after reperfusion, reaching a maximum at 46 h. Brain myeloperoxidase activity, a marker of neutrophil infiltration, was not detected 4 h after reperfusion, but greatly increased at 22 h and then decreased. These results suggest that a marked increase of NOx level in the circulation might reflect the expression of iNOS, while neuronal NOS may contribute to peroxynitrite formation in the cortex observed at an earlier phase of reperfusion. This study indicates that monitoring NOx level in the circulation serves to assess the progress of stroke, and to determine appropriate therapeutic measures.
 ...
PMID:Concurrent formation of peroxynitrite with the expression of inducible nitric oxide synthase in the brain during middle cerebral artery occlusion and reperfusion in rats. 1223 64

Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL-10 on the modulation of the inflammatory response in mice subjected to carrageenan-induced lung injury. When compared to carrageenan-treated IL-10 wild-type (WT) mice, carrageenan-treated IL-10 knock-out mice (IL-10KO) mice experienced a higher rate of pleural exudation, and polymorphonuclear cell migration. Exudate levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1beta and interleukin-6 were also greatly enhanced in IL-10KO mice in comparison to wild-type mice. Lung myeloperoxidase (MPO) activity was significantly reduced in IL-10WT mice when compared to IL-10KO mice-treated with carrageenan. The degree of oxidative and nitrosative damage was significantly higher in IL-10KO mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine and poly (ADP-ribose) synthetase (PARS). Staining of lung tissue sections obtained from carrageenan-treated IL-10WT with an anti-COX-2 antibody showed a positive staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase (iNOS) was found mainly in the macrophages of the inflamed lungs from carrageenan-treated IL-10WT mice. The intensity and degree of the staining for COX-2 and iNOS were markedly enhanced in tissue sections obtained from carrageenan-treated IL-10KO mice. Most notably, the degree of lung injury caused by carrageenan was also enhanced in IL-10KO mice. Taken together, our results clearly demonstrate that endogenous IL-10 exerts an anti-inflammatory role during acute inflammation and tissue damage associated with carrageenan-induced pleurisy, possibly by regulating neutrophil recruitment, and the subsequent cytokine and oxidant generation.
 ...
PMID:Absence of endogenous interleukin-10 enhances the evolution of acute lung injury. 1223 72

Vitamin E is best known for its ability to scavenge reactive oxygen and nitrogen species. Solid tumors are frequently infiltrated with leukocytes, a potential source of these reactive species. The Mutatect tumor model is a fibrosarcoma that can be grown subcutaneously in syngeneic C57BL/6 mice. We previously showed that these tumors are infiltrated with neutrophils and that the number of neutrophils correlates with the number of hypoxanthine phosphoribosyl transferase (hprt) mutations and loss of an interleukin-8 (IL-8) transgene. Neutrophils are a source of nitric oxide, and tumors contain nitrotyrosine, a marker of damage by nitric oxide-related species. We also showed previously that dietary vitamin E supplements markedly lower the frequency of hprt mutants and the level of myeloperoxidase (a neutrophil marker) in a tumor fraction containing "loosely bound" cells. In the present report, we examine the effect of dietary vitamin E in greater detail. No effect on inducible nitric oxide synthase expression or nitrotyrosine levels was observed. However, dietary vitamin E induced a major redistribution of neutrophils from the loosely bound cellular fraction to the "stromal" fraction, while the total number of neutrophils in tumors was essentially unchanged. The loss of the IL-8 transgene seen earlier in Mutatect tumors was largely prevented. Vitamin E also prevented the large increase in hprt mutants (in the cellular and stromal fractions). Thus vitamin E appears to be protective against genotoxicity by scavenging reactive species, but also its ability to affect the distribution of neutrophils within tumors may be important.
 ...
PMID:Dietary vitamin E affects neutrophil distribution and genetic instability in murine Mutatect tumors. 1223 41

Nitric oxide (NO) shows proinflammatory actions mainly via reactive nitrogen species (RNS) formation through superoxide- and peroxidase-dependent mechanisms. The purpose of this study was to examine the role of inducible NO synthase (iNOS) in RNS production, airway hyperresponsiveness, and inflammation after allergen challenge. Ovalbumin (OVA)-sensitised, iNOS-deficient and wild-type mice were used. RNS production was assessed by nitrotyrosine (NT) immunoreactivity in the airways. Airway inflammation and responsiveness were evaluated by eosinophil accumulation and methacholine (i.v.) challenge, respectively. In wild-type mice, OVA-inhalation challenge increased iNOS immunoreactivity in airway epithelial cells as well as iNOS protein measured by Western blotting. The total amounts of nitrite and nitrate in bronchoalveolar lavage (BAL) fluid were increased, and NT immunoreactivity was also observed abundantly in airway inflammatory cells. In iNOS-deficient mice, both iNOS expression and NT formation were completely abolished, and the total amounts of nitrite and nitrate in BAL fluid were significantly decreased. In contrast, OVA-induced airway eosinophil recruitment and hyperresponsiveness were observed almost equally in wild-type and iNOS-deficient mice. These data suggest that reactive nitrogen species production after allergic reaction occurs totally via inducible nitric oxide synthase-dependent pathways. Allergen-mediated airway eosinophil recruitment and hyperresponsiveness appear to be independent of reactive nitrogen species production.
 ...
PMID:iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response. 1235 36

It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum L. Gaertn.), to mouse skin prevents photocarcinogenesis, but the preventive mechanism of photocarcinogenesis in vivo animal system by silymarin is not well defined and understood. To define the mechanism of prevention, we employed immunostaining, analytical assays and ELISA which revealed that topical treatment of silymarin (1 mg/cm2 skin area) to C3H/HeN mice inhibits UVB (90 mJ/cm2)-induced suppression of contact hypersensitivity (CHS) response to contact sensitizer dinitrofluorobenzene. Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%). Silymarin treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine interleukin-10 producing cells and its production (58-72%, p<0.001). Topical treatment of silymarin also resulted in significant reduction of the number of UVB-induced H2O2 producing cells and inducible nitric oxide synthase expressing cells concomitant with decrease in H2O2 (58-65%, p<0.001) and nitric oxide (65-68%, p<0.001) production. Together, these data suggest that prevention of UVB-induced immuno-suppression and oxidative stress by silymarin may be associated with the prevention of photocarcinogenesis in mice. The data obtained from this study also suggest: i) phase-I clinical trial of silymarin in high skin cancer risk human population and ii) development of sunscreen containing silymarin as an antioxidant (chemopreventive agent) or silymarin can be supplemented in skin care products.
 ...
PMID:Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin. 1242 70


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