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)

The effect of the sulfone compound 4,4'-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 mug/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H(2)O(2)-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaI. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the (51)Cr release from virus-induced lymphoma cells. Because the MPO-H(2)O(2)-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system.
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PMID:The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis. 20 42

We studied whether eosinophil peroxidase (EPO), an eosinophil granule basic protein, can alter beta-adrenergic receptor (BAR) density on the guinea pig lung membrane. Lung membrane was first preincubated with 1-10 U/ml EPO and then incubated with 10(-4) M NaI and 10(-4) or 10(-6) M H2O2 for 2 hours. BAR density was determined using (-)125I-cyanopindolol. EPO combined with 10(-4) M H2O2 and I decreased the BAR density in a concentration-dependent manner. When only 10(-4) M H2O2 was used, the decrease in BAR density was small but significant. When compared to I, bromide was less effective and chloride alone was not effective. These results suggest that EPO is one of the factors responsible for beta-adrenergic blockade in asthma.
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PMID:Effect of eosinophil peroxidase on beta-adrenergic receptor density on guinea pig lung membrane. 133 76

The effect of six drugs on the uptake and organification of iodide by porcine thyroid cells stimulated with bovine TSH (10 miU/L) has been investigated. The drugs fall into two categories: the peroxidase inhibitors, methimazole (MMI), 2-thiouracil (2-TU) and 3-amino 1,2,4 triazole (3-ATA) and the ionic inhibitors, lithium chloride (LiCl), potassium perchlorate (KC10(4], and sodium iodide (NaI). All the drugs led to a dose-related inhibition of iodide metabolism. The most potent effect on iodide uptake was seen with NaI which inhibited this function by 20% even at 10(-8) mol/l. In contrast, the most potent effect on iodide organification was observed with methimazole which led to a 25% inhibition at 10(-8) mol/l. The concentrations of drug which gave rise to a 50% inhibition of iodide uptake were (mumol/l) 0.26 (NaI), 3.5 (KClO4), 9.7 (2-TU), 15 (MMI), 26 (3-ATA), and 1500 (LiCl). The comparable figures for organification were 0.13 (MMI), 0.18 (2-TU), 0.23 (NaI), 1.2 (3-ATA), 15 (KClO4) and 1300 (LiCl). We conclude that this in vitro system has considerable potential for the assessment of potency and possible bioassay of anti-thyroid drugs of varying structures and sites of action.
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PMID:Assessment of the biopotency of anti-thyroid drugs using porcine thyroid cells. 243 28

The effectiveness of an antibody-enzyme immunotoxin (eIT) was investigated on human T cells. This enzyme immunotoxin contained glucose oxidase (GO) and lactoperoxidase (LPO) chemically coupled to the pan-leukocyte-specific mouse monoclonal antibody (MoAb) 097 (097-GO and 097-LPO). Human peripheral blood mononuclear cells or tumor cells were suspended in a mixture of 097-GO and 097-LPO for 30 min, and then for 2 h with glucose and NaI. The effectiveness of this eIT system was indicated by the almost complete reduction of T cell viability, as estimated by a phytohemagglutinin induced proliferation assay (99.4% +/- 0.31 depletion, mean +/- SEM of 15 experiments). The specificity of the cytotoxicity reaction was indicated by the lack of cytotoxicity of control irrelevant MoAb conjugates to T cells (1.9% +/- 4.17 of T cell depletion, eight experiments). The growth of human bone marrow myeloid progenitors (CFU-GM) was not affected by the conjugates even by increasing 100-fold the optimal cytotoxic dose. T cells were susceptible to the conjugates in the presence of up to 90% of erythrocytes. This eIT system may thus represent a new alternative immunospecific procedure for allograft and/or autograft purging, and appears to effectively replace complement-mediated methods of T cell depletion.
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PMID:An immunotoxin system intended for bone marrow purging composed of glucose oxidase and lactoperoxidase coupled to monoclonal antibody 097. 279 Mar 30

We have tested the tumoricidal potency of enzyme immunotoxins constructed of antibodies conjugated to glucose oxidase and to lactoperoxidase. Murine plasmacytoma cells were targeted in vitro with the use of affinity-purified rabbit anti-plasmacytoma membrane antibodies (conjugated to glucose oxidase or lactoperoxidase) or rabbit serum raised against plasmacytoma microsome membranes followed by goat anti-rabbit immunoglobulin conjugates (to glucose oxidase or lactoperoxidase). Cytotoxicity was generated subsequently by incubation of the washed cells in a medium supplemented with glucose and sodium iodide, which were the substrates of these enzymes. This resulted in the presumed metabolic release of highly toxic reduced oxygen species and iodinated derivatives. Targeting of tumor cells with both conjugates, as opposed to one of them alone, produced a synergistic killing effect. The gain of specific versus unspecific cytotoxicity was upwards of 10,000-fold. The killing rates were elevated (t10 values less than 30 min) and linear over time. The resultant reduction in tumor cell viability was in the order of 5 to 6 logs after only 20 to 90 min of incubation in the glucose/NaI medium. Cytotoxicity was enhanced by the gamma-glutamyl cysteine synthetase inhibitor buthionine-S,R-sulfoximine and by the glutathione reductase inhibitor 1,3-bis(2-chloroethyl)-1-nitrosourea, while catalase was inhibitory. The results suggest that these enzyme immunotoxins may be suitable for the ex vivo purging of autologous bone marrow grafts.
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PMID:Immunotoxins containing glucose oxidase and lactoperoxidase with tumoricidal properties: in vitro killing effectiveness in a mouse plasmacytoma cell model. 279 Jul 77

Nonopsonized Brucella abortus and bacteria treated with fresh antiserum, heat-inactivated antiserum, or normal bovine serum were evaluated for their ability to stimulate production of superoxide anion and myeloperoxidase-mediated iodination by neutrophils from cattle. Brucella abortus opsonized with fresh antiserum or heat-inactivated antiserum stimulated production of approximately 3 nmol of O2-/10(6) neutrophils/30 min. Similarly treated bacteria also stimulated the binding of approximately 4.3 nmol of NaI/10(7) neutrophils/h to protein. Significant (P less than 0.05) production of O2- and iodination activity by neutrophils were not stimulated by nonopsonized bacteria or organisms treated with normal bovine serum. Seemingly, B abortus stimulated oxidative metabolism in bovine neutrophils; however, the stimulation was dependent on the presence of bacterial associated opsonins.
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PMID:Opsonin-dependent stimulation of bovine neutrophil oxidative metabolism by Brucella abortus. 283 60

Ascaridole, an asymmetric monoterpene endoperoxide with anthelmintic properties, occurs as a major constituent (60-80%) in the volatile oil of American wormseed fruit (Chenopodium ambrosioides: Chenopodiaceae), and as a lesser component in the leaf pocket oil of the boldo tree (Peumus boldus: Monimiaceae). Determination of optical activity and chromatographic resolution of naturally occurring ascaridole, and several synthetic derivatives, showed that both wormseed and boldo produce ascaridole in racemic form. The biosynthesis of ascaridole from the conjugated, symmetrical diene alpha-terpinene (a major component of the oil from wormseed) was shown to be catalyzed by a soluble iodide peroxidase isolated from homogenates of C. ambrosioides fruit and leaves. The enzymatic synthesis of ascaridole was confirmed by capillary gas-liquid chromatography and mass spectrometry of the product, which was also shown to be racemic. Optimal enzymatic activity occurred at pH 4.0 in the presence of 2.5 mM H2O2 and 1 mM NaI. Soluble enzyme extracts were fractionated by gel filtration on both Sephacryl S-300 and Sephadex G-100, and were shown to consist of a high-molecular-weight peroxidase component (Mr greater than 1,000,000, 30% of total activity) and two other peroxidase species having apparent molecular weights of 62,000 and 45,000 (major component). Peroxidase activity was susceptible to proteolytic destruction only after periodate treatment, suggesting an association of the enzyme(s) with polysaccharide material. Ascaridole biosynthesis from alpha-terpinene was inhibited by cyanide, catalase, and reducing agents, but not by compounds that trap superoxide or quench singlet oxygen. A peroxide transfer reaction initiated by peroxidase-generated I+ is proposed for the conversion of alpha-terpinene to ascaridole.
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PMID:Biosynthesis of ascaridole: iodide peroxidase-catalyzed synthesis of a monoterpene endoperoxide in soluble extracts of Chenopodium ambrosioides fruit. 649 93

The antimicrobial oxidative system (myeloperoxidase (MPO), H2O2 and a halide) produced by stimulated PMNLs is simulated in vitro using horseradish peroxidase (HRP), H2O2 and NaI. Ascorbate, thiamine, levamisole and cysteine prevent and reverse the PMNL motility inhibiting effects of the HRP/H2O2/NaI system. The ability of these agents to protect the PMNL specifically from the known iodinating and oxidising abilities of this system was investigated. All four agents protect the PMNL from iodination by HRP/H2O2/NaI. However, only ascorbate and thiamine are able to reverse this process after it has occurred. Thiamine is seen on thin layer chromatography followed by autoradiography to be iodinated by this system. Ascorbate, thiamine and cysteine are able to protect the neutrophil sulfhydryl groups from oxidation by the system. One can therefore conclude that ascorbate and cysteine protect neutrophil motility from inhibition by the HRP/H2O2/NaI system by acting as reducing agents which maintain the neutrophil sulfhydryl groups. Thiamine also acts as a reducing agent, though not as effectively as ascorbate or cysteine. In addition, thiamine protects the PMNL from iodination by a competitive mechanism. The mechanism of levamisole protection is less clear but may involve scavenging of free radicals generated by the HRP/H2O2/NaI system. Protease enzymes, glycolysis and adherence are found not to be target sites for the PMNL motility inhibiting effects of the HRP/H2O2/NaI system. Further, increasing concentrations of the synthetic leukoattractant FMLP were shown to increase the auto-iodination of PMNLs without addition of extraneous peroxidase or peroxide. This data was compared with optimal FMLP concentrations for chemotaxis.
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PMID:Oxidative inhibition of polymorphonuclear leukocyte motility mediated by the peroxidase/H2O2/halide system: studies on the reversible nature of the inhibition and mechanism of protection of migratory responsiveness by ascorbate, levamisole, thiamine and cysteine. 665 35

Cefdinir, a new oral 2-amino-5-thiazolyl cephalosporin, inhibited the luminol-amplified chemiluminescence (LACL) response of human neutrophils stimulated by PMA but not opsonized zymosan, in a concentration-dependent but not time-dependent manner. The LACL response to opsonized zymosan in cytochalasin B-treated neutrophils was, however, inhibited by cefdinir. Various cephalosporins, regardless of the presence of a 2-amino-5-thiazolyl moiety, did not significantly alter the neutrophil LACL response triggered by PMA and zymosan. The LACL response induced by the calcium ionophore A23187 and FMLP was also impaired by cefdinir, and this impairment was increased in cytochalasin B-treated neutrophils. Superoxide anion generation by neutrophils, measured in terms of lucigenin-amplified chemiluminescence and cytochrome c reduction, was not altered. Spontaneous and FMLP-induced neutrophil degranulation, assessed by lysozyme and beta-glucuronidase release, were not modified by cefdinir. Furthermore, cefdinir inhibited LACL generation in cell-free systems consisting of H2O2, NaI, and either horseradish peroxidase or a myeloperoxidase-containing neutrophil extract. Orthodianisidine oxidation in these two acellular systems was inhibited by cefdinir. Cefdinir did not alter neutrophil bacterial killing at concentrations that inhibited myeloperoxidase-containing neutrophil extract-dependent reactions induced by soluble stimuli. Taken together, these data strongly suggest that cefdinir directly inhibits the activity of myeloperoxidase-containing neutrophil extract released into the extracellular medium during neutrophil stimulation by soluble mediators, but has no effect on that released into the phagolysosome during phagocytosis. This unusual property of a member of the beta-lactam family could be of interest in modulating the exaggerated inflammatory process often associated with infectious diseases.
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PMID:Cefdinir (CI-983), a new oral amino-2-thiazolyl cephalosporin, inhibits human neutrophil myeloperoxidase in the extracellular medium but not the phagolysosome. 813 56

Thyroid peroxidase (TPO) is well known to be an essential enzyme for the biosynthesis of thyroid hormone. The changes of TPO activities in thyroid tissue have already been reported in pathophysiological and experimental conditions by several assay methods. Most of these assay methods, however, need relatively large amounts of tissue (over 10mg wet tissue) to obtain enzyme fraction for assay by homogenization and fractionation of the tissue. Therefore, it is difficult to apply these methods to relatively small numbers (less than 10(6) cells) of thyroid cells. In the present study, we attempted to develop a new and simple method for the assay of TPO activity using tetramethylbenzidine (TMB) as substrate. The reaction mixture were composed of 250 microliters of commercially available tetramethylbenzidine solution containing H2O2 (TM-Blue; TSI-CDP) and 250 microliters of cell lysate obtained by freeze-thawing in 0.1M citrate buffer (pH 4.8). Various doses of known amounts of horseradish peroxidase (HRP; 0-1000 microU) were assayed as a standard at the same time. TPO activity in cell lysate was expressed as the activity corresponding to HRP activity. In this assay method, TPO activity of sonicated-cell lysate was higher than that of nonsonicated-cell lysate, and the activity in sonicated cell lysate was linearly correlated with cell numbers. Next, the effects on the TPO activity of the direct addition of various agents into the reaction mixture were also examined. Both methylmercaptoimidazole (MMI) and NaN3 strongly inhibited TPO activity in sonicated-cell lysate as well as in mitochondria-microsomal fraction of thyroid tissue with the respective IC50 value of less than 5 microM and less than 0.1 mM. In the present method, the authors could demonstrate the following: 1) After 4 days of suspension culture with TSH (0.5 mU/ml), TPO activity of the follicles increased 3.2-5.6 fold when compared with that cultured in the absence of TSH. 2) (Bu)2cAMP (DBC; 1 mM) and forskolin (20 microM) also increased TPO activity of the follicles by 2.9-5.2 and by 2.9-6.2 fold. 3) The addition of NaI (0-100 microM) into medium dose-dependently inhibited the induction of TPO activity by TSH. 4) EGF (10(-8) M) and PMA (10(-6) M) as well as NaI (100 microM) also inhibited the induction of TPO activity in the follicles by TSH, DBC and forskolin during culture for 4 days. Accordingly, it is indicated that these agents may inhibit an induction of TPO activity at least in part at the step of post-cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A simple assay of peroxidase activity in cultured thyroid follicles using tetramethylbenzidine as substrate]. 833 Jun 56


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