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:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat hind-paw swelling was induced dose-dependently by subplantar injection of acidic phospholipase A2 (NNAVPLA2) from Naja naja atra venom. Diphenhydramine and methysergide pretreatment greatly reduced the swelling effect caused by NNAVPLA2. Several doses of compound 48/80 given to deplete the histamine content of rat hind paw, also greatly suppressed NNAVPLA2-induced paw swelling. The paw swelling caused by NNAVPLA2 was reduced following pretreatment with BW 755C, a dual inhibitor of cyclooxygenase/lipoxygenase, or subplantar co-injection with FPL 55712, a SRS-A antagonist, while pretreatment with acetylsalicylic acid had no effect. Captopril significantly potentiated the NNAVPLA2-induced paw swelling. The recovered myeloperoxidase activity was increased within 1 h and still elevated in the rat paw 3 to 6 h after subplantar injection of NNAVPLA2. In isolated peripheral PMN leukocyte suspension, NNAVPLA2 caused a release of superoxide radical. Subplantar co-injection with superoxide dismutase/catalase significantly inhibited NNAVPLA2-induced paw swelling. NNAVPLA2 did not trigger platelet aggregation either in platelet-rich plasma or in washed platelet suspension. NNAVPLA2-induced hind-paw swelling was also suppressed by the pretreatment with isoprenaline or terbutaline, while this response was not affected by co-injection with BN 52021, a PAF antagonist, into the paw. It is concluded that the hind-paw swelling caused by NNAVPLA2 is mainly due to histamine and serotonin released from mast cells and partly due to the formed kinins and SRS-A in the inflammatory area, and superoxide radical from PMN leukocytes.
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PMID:Effects of anti-inflammatory drugs on rat hind-paw swelling caused by phospholipase A2 from Naja naja atra venom. 168 89

Unstimulated normal human blood platelets were treated with azodicarboxylic acid bis(dimethylamide) (diamide), a thiol-oxidizing agent. Oxygenated arachidonic acid (AA) metabolites, malondialdehyde (MDA), and tocopherols were then quantified by high-performance liquid chromatography (HPLC). Diamide treatment partially decreased the amount of reduced glutathione (GSH) content and induced a subsequent decrease in peroxidase activity. However, formation of 12-hydroxy-eicosatetraenoic acid (12-HETE), the end-product of lipoxygenation of AA, increased. Formation of MDA, a marker of overall lipid peroxidation, was also enhanced. Furthermore, platelet alpha-tocopherol, but not gamma-tocopherol, significantly decreased. These results indicate that enhanced "basal" lipoxygenase activity, as a marker of specific AA oxygenation, may be linked to decreased platelet antioxidant status.
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PMID:Decrease in platelet reduced glutathione increases lipoxygenase activity and decreases vitamin E. 176 13

We examined the immunohistochemical distribution of the arachidonate 12- and 15-lipoxygenases in animal and human lung tissue using a polyclonal anti-12/15-lipoxygenase antibody. Immunoblotting of whole cell extracts from bovine and human tracheal epithelial cells or from bovine leukocytes with the antibody (raised originally against purified porcine leukocyte 12-lipoxygenase) showed immunoperoxidase staining of a single protein band (Mr = 72,000), which comigrated with purified bovine 12-lipoxygenase. The antibody also immunoprecipitated both 12- and 15-lipoxygenase activities from cytosolic fractions of bovine and human tracheal epithelial cells. Immunohistochemistry of formaldehyde-fixed and paraffin-embedded bovine (and ovine and canine) trachea using the same polyclonal antibody and an indirect biotin-avidin-peroxidase detection system demonstrated specific staining of tracheal epithelium, polymorphonuclear and mononuclear leukocytes, and perineural cells. Less intense staining of submucosal glands and blood vessels was also observed. Lung sections demonstrated that the level of lipoxygenase antigen decreased markedly by the level of the bronchi and was absent in more distal airways. A similar pattern of immunostaining was found in human lung, except that airway smooth muscle was also weakly reactive, and polymorphonuclear (neutrophilic) leukocytes were unstained (in accordance with the low 12/15-lipoxygenase activity in this cell type). We conclude that animal and human epithelial 12/15-lipoxygenases share enzymatic, antigenic, and regional distribution characteristics and may therefore possess a common function in the pulmonary airway.
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PMID:Related expression of arachidonate 12- and 15-lipoxygenases in animal and human lung tissue. 176 60

Concentrations of 5-, 12-, 15-HETE versus myeloperoxidase activity in the periulcerous area were investigated in 40 peptic ulcer patients. A control group consisted of 20 healthy subjects. In ulcer patients the activity of lipoxygenase pathway of metabolism of arachidonic acid and myeloperoxidase was enhanced. This is likely to promote chronic inflammation of the mucosa in the periulcerous area, this inflammation being an important prognostic factor for ulcerogenesis.
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PMID:[Synthesis of lipoxygenase metabolites of arachidonic acid and their role in the pathogenesis of inflammation of gastric mucosa]. 180 57

An enzymatic activity has been found in cytosolic preparations from mouse epidermis which catalyzes the formation of 8-hydroperoxyeicosatetraenoic acid/8-hydroxyeicosatetraenoic acid (8-HPETE/8-HETE) from arachidonate. In contrast to 12-lipoxygenase this enzyme activity was not detectable in normal (untreated) mouse skin but only after in vivo treatment with the phorbol ester tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). The induction showed a maximum at 24 h after TPA treatment strictly depended on the age of the mice and the TPA dose and was prevented by cycloheximide. The primary product formed from arachidonic acid was 8-HPETE, and the enzyme seems not to possess a significant peroxidase activity. This result as well as studies with specific inhibitors and its cytosolic localization indicates this enzyme to be a member of the lipoxygenase family. Most of the 8-lipoxygenase activity is located in cells of the suprabasal compartment of the epidermis. In spite of being a cytosolic enzyme 8-lipoxygenase appeared to be lipophilic to some extent and was activated by lecithin. The enzyme did not require calcium ions or ATP and showed a pH optimum at 7.5-8.0. 8-HPETE/8-HETE levels in mouse epidermis in vivo were determined by gas chromatography-mass spectrometry and found to be strongly increased after phorbol ester treatment, in agreement with the induction of 8-lipoxygenase observed.
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PMID:Characterization of an 8-lipoxygenase activity induced by the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate in mouse skin in vivo. 187 32

Ebselen (PZ 51, 2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) is a selenoorganic compound with anti-inflammatory properties. Its pharmacological action is thought to originate from its peroxidase activity which could lower the peroxide tonus required for cyclooxygenase and lipoxygenase activations. From experiments with aspirin-treated human platelets we now present evidence that ebselen also affects intracellular calcium homeostasis by inhibiting the agonist-triggered increase in intracellular calcium. Using Mn2+ entry to quench the fura-2 fluorescence after cell stimulation, we could exclude an interaction of ebselen with receptor-operated calcium channels and therefore an inhibition of extracellular calcium influx. It became evident from whole cell experiments and by using isolated platelet microsomal vesicles that ebselen inhibits the inositol 1,4,5-trisphosphate (IP3) induced calcium release. Besides this inhibitory effect of ebselen on the calcium release higher concentrations of the compound (greater than or equal to 5 microM) induced a calcium release from our microsomal vesicles which also could be reversed by dithiothreitol. An activation of inflammatory cells is usually associated with increased cytosolic calcium concentrations. An inhibition of such calcium movements by ebselen may account for an up to now unidentified anti-inflammatory mechanism of ebselen action which is linked to a direct effect of this compound rather than to its peroxidase-like activity.
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PMID:Ebselen affects calcium homeostasis in human platelets. 203 37

Activation of arachidonic acid occurs after spinal cord injury. Leukotriene B4 is a lipoxygenase metabolite of arachidonic acid. In a rat model of experimental spinal cord injury, we found that the leukotriene B4 content was less than the sensitivity of our assay (8 pg/mg of protein) in non-traumatized spinal cord. Leukotriene B4 was detectable in traumatized cord (mean +/- SE, 25 +/- 5 pg/mg of protein; n = 3). Release of leukotriene B4 from spinal cord slices into the incubation medium was also noted after trauma (9 +/- 1 pg/mg of protein; n = 12) and was enhanced by exposure of traumatized spinal cord slices to the calcium ionophore A23187 (375 +/- 43 pg/mg of protein; n = 12). The amount of leukotriene B4 released corresponded to the extent of post-traumatic polymorphonuclear cell infiltration determined by a myeloperoxidase assay. Results from this study suggest that the source of leukotriene B4 in spinal cord injury is infiltrating polymorphonuclear cells.
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PMID:Leukotriene B4 release and polymorphonuclear cell infiltration in spinal cord injury. 216 76

Several studies have demonstrated that granulocytes accumulate in the intestinal mucosa following ischemia/reperfusion. It has been suggested that leukotriene B4 may be released during ischemia/reperfusion and consequently may promote granulocyte infiltration into the mucosa. The objectives of this study were to determine whether (a) leukotriene B4 is produced in the gut mucosa during ischemia and reperfusion, and (b) inhibition of leukotriene B4 attenuates granulocyte infiltration into the postischemic intestinal mucosa. Isolated segments of cat intestine were subjected to 3 hours of ischemia and 1 hour of reperfusion. Mucosal samples were obtained during baseline, ischemia at 3 hours and reperfusion at 1 hour. Leukotriene B4 production was determined by radioimmunoassay. Tissue-associated myeloperoxidase activity was used to quantitate granulocyte accumulation in the mucosal samples. In untreated animals, mucosal leukotriene B4 concentration was higher at reperfusion compared with baseline levels. The reperfusion-induced increase in mucosal leukotriene B4 was entirely prevented by pretreatment with either nordihydroguaiaretic acid (Sigma Chemical Co., St. Louis, MO) or L663,536 (Merck-Frosst, Montreal, Quebec, Canada), two potent lipoxygenase inhibitors. Both lipoxygenase inhibitors, as well as leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes. These results indicate that leukotriene B4 plays an important role in mediating the granulocyte accumulation elicited by reperfusion of the ischemic bowel.
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PMID:Role of leukotriene B4 in granulocyte infiltration into the postischemic feline intestine. 217 Feb 22

Alveolar macrophages (AMs) and mast cells reside in the airway, and both have been demonstrated to contribute independently to allergic inflammatory responses through the generation of respiratory-burst metabolites and the release of biologically active mediators, respectively. Since mast cell granules (MCGs) contain mediators that could potentially interact with the AM respiratory burst, we investigated the effects of isolated MCGs on this important inflammatory pathway of the AM. MCGs and AMs were obtained by peritoneal and tracheoalveolar lavage, respectively, of Sprague-Dawley rats. First, the overall respiratory-burst activity was measured by luminal-enhanced chemiluminescence (CL), and second, the individual oxygen species contributing to CL (superoxide anion [O2-], hydrogen peroxide [H2O2], and hypochlorous acid) were measured. MCGs alone enhanced AM CL responses to an equivalent degree compared to zymosan-stimulated AMs. However, AMs preincubated with MCGs followed by zymosan stimulation significantly and synergistically enhanced the CL responses. This enhanced CL was not due to an increased production of O2-, H2O2, or hypochlorous acid; in fact, there were decreased measured amounts of O2- and H2O2 from zymosan-stimulated AMs in the presence of MCGs, most likely caused by the content of granules of superoxide dismutase and peroxidase, respectively. The lipoxygenase inhibitor, nordihydroguaiaretic acid, completely abolished the enhanced CL of AM preincubated with MCGs and subsequently stimulated by zymosan, but O2- production was not affected by nordihydroguaiaretic acid. Taken together, these results suggest that derivatives of arachidonic acid metabolism, most likely those of the lipoxygenase pathway, are responsible for the enhanced AM CL response observed in the presence of MCGs. Thus, mast cell-macrophage interactions may be important within the airway in enhancing the generation of mediators that contribute to tissue inflammation and bronchospasm.
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PMID:Mast cell granules modulate alveolar macrophage respiratory-burst activity and eicosanoid metabolism. 217 47

We examined the characteristics of an arachidonate 12-lipoxygenase in bovine tracheal epithelial cells in relation to the enzyme expressed in leukocytes and platelets. Homogenous preparations of intact or disrupted tracheal epithelial cells metabolized arachidonic acid predominantly to (12S)-hydroxyeicosatetraenoic acid, and subcellular fractionation by differential centrifugation demonstrated that the 12-lipoxygenase activity was localized predominantly to the 100,000 x g supernatant (cytosol fraction). Analysis of cytosolic enzymatic activity for pH dependence (maximum activity at pH 7.4-8.0), divalent cation effects (no dependence on cations), and kinetic characteristics (lag phase elimination by addition of hydroperoxide) exhibited similarity to leukocyte and platelet 12-lipoxygenases. Immunoprecipitation experiments demonstrated that the epithelial 12-lipoxygenase reacted with a monoclonal antibody (lox-2) directed against leukocyte 12-lipoxygenase but not with an antibody (HPLO-3) against the platelet enzyme. Immunoaffinity chromatography of the epithelial 100,000 x g supernatant fraction using lox-2 linked to Affi-Prep 10 yielded a single predominant protein band (Mr = 72,000) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis identical in apparent mass to the bovine leukocyte lipoxygenase. Western blotting using a polyclonal antibody to leukocyte 12-lipoxygenase showed peroxidase staining of the same 72-kDa protein band. Activity assays of the purified enzymes demonstrated that substrate specificity for the epithelial 12-lipoxygenase was similar to that of the leukocyte enzyme, but the epithelial enzyme more efficiently converted 18-carbon fatty acids to the corresponding monohydroxylated conjugated dienes. We conclude that bovine tracheal epithelial cells express a 12-lipoxygenase that has immunological reactivity similar to leukocyte and distinct from platelet 12-lipoxygenase and possesses substrate specificity distinct from both enzymes. We further suggest that lipoxygenase heterogeneity may provide a basis for different functional roles for the enzyme in different cell types.
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PMID:Identification of a novel arachidonate 12-lipoxygenase in bovine tracheal epithelial cells distinct from leukocyte and platelet forms of the enzyme. 229 56


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