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)

Eosinophil granules contain several cationic proteins that mediate tissue damage in allergic disease. The present study examined the capacity and mechanisms by which these cationic proteins regulate activity of the alternative pathway of C. Eosinophil peroxidase and eosinophil cationic protein inhibited formation of cell-bound alternative pathway C3 convertase, causing 50% inhibition of lysis at about 0.19 and 0.75 microgram/10(7) cellular intermediates, respectively. Major basic protein inhibited alternative pathway C3 activity by only 19% at 1.5 micrograms/10(7) cellular intermediates. Eosinophil-derived neurotoxin had no activity on the alternative pathway. The eosinophil granule proteins were examined for the mechanism by which they inhibited alternative pathway activity. Eosinophil peroxidase and major basic protein inhibited fluid phase factor B consumption in a reaction mixture that also contained factors D and C3b, eosinophil-derived neurotoxin had no activity on factor B consumption, and eosinophil cationic protein consumed factor B in the absence of C3b and factor D. Both eosinophil cationic protein and eosinophil peroxidase enhanced the decay of preformed alternative pathway convertase. Lysis of EAC4b,3b cellular intermediates formed to contain a low surface amount of C3b was more inhibited than was lysis of cells formed with a standard amount of C3b on the surface. This suggests that these eosinophil proteins acted predominantly on C3b to regulate alternative pathway activity. We also found that none of the eosinophil granule cationic proteins had any effect on later events after the formation of the C3 convertase. We conclude that although eosinophil-derived neurotoxin (isoelectric pH value (pI) = 8.9) does not regulate alternative pathway activity, the more highly charged eosinophil granule cationic proteins--major basic protein (pI = 10.9), eosinophil cationic protein (pI = 10.8), and eosinophil peroxidase (pI = 10.8)--do share the capacity to regulate C activity and may exert this activity in vivo.
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PMID:Eosinophil granule cationic proteins regulate complement. I. Activity on the alternative pathway. 162 7

The eosinophil granule major basic protein, the eosinophil cationic protein, and the eosinophil-derived neurotoxin were found to be lytic for Trypanosoma cruzi trypomastigotes from blood, cell cultures, or insect vectors and for cultured amastigotes. The toxic effects of the major basic and cationic proteins were inhibited by the polyanions heparin and dextran sulfate, in keeping with the cationic nature of these proteins, or by heat denaturation, suggesting that molecular conformation was also relevant. The lytic activity of the neurotoxin was not inhibited by heating at 56 degrees C for 4 hr, establishing an additional difference with the eosinophil cationic protein. Heparin had only a slight inhibitory effect on the toxicity of the neurotoxin, and dextran sulfate was inactive even at 25 mg/ml. Although both the eosinophil cationic protein and the neurotoxin possess ribonuclease activity, only the toxicity of the latter was abolished by the ribonuclease inhibitor RNasin (Promega, Madison, Wisconsin) or by a competitive substrate, yeast ribonucleic acid. Eosinophil peroxidase significantly increased the extent of trypomastigote or amastigote killing by hydrogen peroxide in the presence of iodide. This effect was abrogated by sodium azide, bovine serum albumin, or gelatin, known inhibitors of the eosinophil peroxidase + halide + hydrogen peroxide system. These results suggest that the destruction of T. cruzi trypomastigotes and amastigotes by eosinophils may result from toxic mechanisms involving several granule proteins.
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PMID:Toxic effects produced or mediated by human eosinophil granule components on Trypanosoma cruzi. 245 44

Eugenol has recently been associated with the toxic effects of clove cigarettes on human lungs. We have studied the metabolism and adverse effects of eugenol on human polymorphonuclear leukocytes (PMNs). Myeloperoxidase, isolated and purified from human PMNs, catalyzed the oxidation of eugenol to a reactive intermediate which is likely to be a quinone methide. Eosinophil peroxidase, lactoperoxidase, prostaglandin H synthase, horseradish peroxidase, and rat intestinal peroxidase also supported this hydrogen peroxide dependent reaction. Glutathione inhibited the formation of this metabolite, resulting in the formation of glutathione disulfide and a small amount of eugenol-glutathione conjugates. In cellular incubations, phorbol ester stimulated PMNs catalyzed the covalent binding of [3H]eugenol to cellular protein, which was partially inhibitable by azide. Intracellular glutathione levels decreased by 90% over a period of 30 min in phorbol ester stimulated PMNs exposed to 100 microM eugenol compared with decreases of 30% (phorbol ester alone) or 5% (eugenol alone) in control incubations. In addition, eugenol was more cytotoxic to PMNs in the presence of phorbol ester than in its absence, and eugenol inhibited the phorbol ester stimulated oxidative burst in PMNs as reflected by a decrease in oxygen consumption, superoxide formation, and hydrogen peroxide formation. These results suggest that PMNs are capable of activating eugenol to a reactive intermediate and also suggest a mechanism whereby eugenol can potentially interfere with and adversely affect vital PMN functions.
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PMID:Metabolic activation of eugenol by myeloperoxidase and polymorphonuclear leukocytes. 256 21

In estrogen and diethylstilbestrol-treated rats, uterine peroxidases originate from two sources, the infiltrating eosinophils (exogenous) and the uterine tissue itself (endogenous). The study reported here distinguished the exogenous peroxidases by biochemical means and by cytochemistry. Eosinophil peroxidases are confined to the stromal and myometrial regions and appear simultaneously with endogenous peroxidases. At 48 h after estrogen-administration, the clear uterine luminal washings contain five peroxidase isoforms; this increases to 7-15 isozymes by 72 h. Uterine fluid peroxidase isozymes are acidic proteins with pI values ranging from pH 4.0 - 7.2, while the principal eosinophil peroxidase is a basic protein with a pI value ranging from pH 8.0-8.9. Eosinophil peroxidase is electrophoretically demonstrable only in the presence of the cationic detergent cetyltrimethyl ammonium bromide (CTAB) and has a spectrophotometric optimum of pH 4.4. In contrast, uterine fluid peroxidases have a pH optimum of 7.2. and no requirement for CTAB. Uterine tissue peroxidase extracted in the presence of Ca2+, showed a minor electrophoretic peroxidase band in the acidic pH range; however, a CTAB-activated peroxidase similar to the principal eosinophil peroxidase appeared as a basic protein. The data strongly suggest that uterine fluid peroxidases are estrogen-induced peroxidases (EIP) distinct from the eosinophil peroxidases that are largely restricted to the stromal compartment. This conclusion is supported by cytochemical studies that show two eosinophilperoxidases. The one shown by DAB was resistant to cyanide whereas the one shown by PPD/PC was inhibited by cyanide. A uterine tissue peroxidase, which was demonstrated only in stromal cells by the DAB medium, was more sensitive to cyanide than the eosinophil peroxidase shown by DAB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peroxidases induced in rat uterus by estrogen administration. II. Cytochemical and biochemical heterogeneity. 378 93

Eosinophil peroxidase (EPO) at relatively low levels (4-30 mU), when supplemented with H2O2 and a halide, induced mast cell degranulation. Histamine release occurred without concomitant release of the cytoplasmic marker lactic dehydrogenase (LDH), and this, together with ultrastructural studies, indicated a noncytotoxic effect comparable with that induced by other mast cell secretagogues. At pH 7.4, iodide was effective at concentrations down to 10(-5) M, and although chloride alone was ineffective at 0.1 M, a combination of 0.1 M chloride and 10(-6) iodide could meet the halide requirement. Chloride alone was effective at pH 6.5 and 6.0. EPO could be replaced by myeloperoxidase. When the EPO level was increased to 100 mU, combination with H2O2- and iodide-induced cytotoxic histamine release as indicated by concomitant LDH release and ultrastructural evidence of cell disruption. This cytotoxic response reverted to a secretory one on the addition of albumin. Peroxidase was detected on the surface of extruded granules by diaminobenzidine cytochemistry. The mast cell granule (MCG)/EPO complex when supplemented with H2O2 and iodide was more effective than free EPO in the stimulation of mast cell secretion. The stimulation of mast cell mediator release by the EPO-H2O2-halide system and the formation of MCG/EPO complexes with augmented cytotoxic activity may influence the adjacent inflammatory response.
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PMID:Eosinophil peroxidase-induced mast cell secretion. 615 83

Forty-five subjects with a complete deficiency of myeloperoxidase were identified in an area of the region Friuli-Venezia Giulia in north-eastern Italy using the Hemalog D system as the screening technique. Histochemical and biochemical tests performed on the leucocytes of some of these subjects confirmed the defects shown by the Hemalog D system. The defect was of genetic origin in seven subjects. The genetic origin could be suspected in another eight subjects since more than two affected members were present in a given family. Eosinophil peroxidase, which is present in MPO deficient subjects, interfered with the guaiacol assay of MPO, and in several cases masked the genetic transmission. An assay was developed using o-dianisidine as the electron donor which considerably reduced the interference by EPO. With this assay an autosomal recessive pattern of inheritance was found. The MPO deficient leucocytes had a higher respiratory burst than control cells and an impaired bactericidal activity, at early post-phagocytic periods, which became comparable to that of control cells at later stages. Particle ingestion by the MPO-deficient cells was normal.
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PMID:Incidence of myeloperoxidase deficiency in an area of northern Italy: histochemical, biochemical and functional studies. 628 Jul 44

Eosinophil peroxidase (donor:hydrogen peroxide oxidoreductase, EC 1.11.1.7) was isolated from outdated human white blood cells. The purified enzyme has a molecular weight of 71000 +/- 1000. The enzyme is composed of two subunits, of Mr 58000 and 14000, in a 1:1 stoichiometry. Amino-acid analyses showed that eosinophil peroxidase has a high content of the amino acids arginine, leucine and aspartic acid. The millimolar absorbance coefficient of the Soret band at 412 nm of eosinophil peroxidase was determined. Three independent methods yield a value for epsilon 412nm of 110 +/- 4 mm-1 X cm-1. Purified eosinophil peroxidase showed a homogeneous high-spin EPR signal with rhombic symmetry (gx = 6.50; gy = 5.40; gz = 1.982) for the haem group. EPR spectroscopy of low-spin cyanide and azide derivatives of eosinophil peroxidase, lactoperoxidase, myeloperoxidase and catalase revealed that the haem-ligand structure of eosinophil peroxidase is closely related to lactoperoxidase, whereas that of myeloperoxidase shows great resemblance to catalase.
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PMID:Some properties of human eosinophil peroxidase, a comparison with other peroxidases. 631 32

Heme-containing peroxidases have been demonstrated both biochemically and cytochemically in a variety of cells that either reside in the respiratory tract or circulate through it via the vasculature. The peroxidases in neutrophils and eosinophils have long been known to function in lung defense through their participation in an antimicrobial system involving hydrogen peroxide and chloride ions. Recent studies indicate that this system is also toxic to tumor cells and, as such, it may have a protective or mitigative effect on tumor formation in the lung. Eosinophil peroxidase may be involved in immediate hypersensitivity reactions in the lung because of its secretory effect on mast cells. Platelets contain peroxidases, but how they function is unknown. Whether peroxidase occurs in lymphocytes is controversial, but until more compelling evidence is presented they should be considered peroxidase-negative. A number of cells indigenous to the respiratory tract contain peroxidase activity, but there is considerable variability among species as to its presence and amount. When careful consideration is given to fixation and incubation conditions, peroxidase can be demonstrated cytochemically in the nuclear envelope and endoplasmic reticulum of some endothelial cells and type II cells of certain rodents, but its physiological role is speculative. The alveolar macrophages of most species possess little or no peroxidase activity apart from catalase which can function as a peroxidase under certain conditions. Mast cells in the respiratory tract contain peroxidase, but it is more easily demonstrated biochemically than cytochemically. The function of mast cell peroxidase is unknown, but two hypotheses worthy of investigation are its possible role in modulation of atopic allergic reactions and involvement in an antitumor defense mechanism similar to that of myeloperoxidase. Peroxidase is most abundant in the secretory cells of the tracheobronchial epithelium and glands where, in a number of species, it is synthesized and secreted as a component of mucus. Its possible contribution to lung defense is discussed in view of its morphologic similarity to the antibacterial peroxidase of milk and saliva. Because of the ease with which peroxidases can be demonstrated cytochemically, it is not surprising that morphologic information regarding their distribution in the respiratory tract has greatly exceeded insights into their functional significance. It is hoped that advancements in cell dissociation and culture, along with biochemical isolation and purification techniques, will lead to definitive conclusions concerning their physiologic roles in lung metabolism and defense.
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PMID:The distribution and function of peroxidases in the respiratory tract. 638 50

Eosinophil peroxidase (EPO), a cationic protein purified from horse blood, adhered to four different types of tumor cells, markedly potentiating their lysis by preformed or enzymatically generated H(2)0(2) (up to 76-fold, as assayed in serum-containing tissue culture medium without supplemental halide). Similarly, compared with uncoated tumor cells, EPO-coated tumor cells were up to 32 times more sensitive to lysis when incubated with macrophages or granulocytes whose respiratory burst was triggered by PMA. However, EPO-coated tumor cells were also readily lysed by bacillus Calmette- Guerin-activated macrophages in the absence of exogenous triggering agents. This spontaneous cytolysis was rapid (50 percent at 2 h) and potent (50 percent lysis at macrophage/tumor cell ratios of 1.5 to 4.6), and was observed with both a peroxide-sensitive tumor (TLX9) and a peroxide-resistant tumor (NK lymphoma). Under the conditions used, neither EPO alone nor macrophages alone were spontaneously cytolytic. Neither EPO nor EPO-coated tumor cells triggered a detectable increment in H(2)0(2) release from macrophages. Nonetheless, spontaneous macrophage-mediated cytolysis of EPO- coated tumor cells was completely inhibitable by catalase (50 percent inhibition, 23 U/ml), although not by heated catalase, indicating a requirement for H(2)0(2). Cytolysis was also completely inhibitable by azide (50 percent inhibition, 2.6 X 10 -5 M), indicating a requirement for enzymatic activity of EPO. Thus, a cytophilic peroxidase from eosinophils and H(2)0(2) spontaneously released from activated macrophages interacted synergistically in a physiologic medium to destroy tumor cells.
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PMID:Augmentation of spontaneous macrophage-mediated cytolysis by eosinophil peroxidase. 680 24

Eosinophil peroxidase (EPO) and to a lesser degree neutrophil peroxidase (myeloperoxidase, MPO) bound tightly to mast cell granules (MCG), particularly when the latter were depleted of histamine by suspension in physiologic salt solutions. The bound EPO was localized on the surface of the granule, and its dissociation required salt concentrations of high enough ionic strength (greater than 0.75 M) to solubilize the MCG matrix. Elution of MPO from the complex occurred at a lower salt concentration. The MCG/EPO complex retained the capacity of the isolated EPO to catalyze the iodination reaction when supplemented with iodide, H2O2, and a protein acceptor and to kill microorganisms when supplemented with H2O2 and a halide (iodide, chloride). Indeed, the MCG/EPO complex had significantly greater iodinating and bactericidal activity than the free enzyme when standardized to equal guaiacol units of peroxidase activity. Thus, in areas of inflammation where mast cells and phagocytic leukocytes coexist, there is the potential for the formation of active complexes extracellularly between mast cell granules and molecules such as EPO (or MPO) that can affect the inflammatory response.
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PMID:Binding of eosinophil peroxidase to mast cell granules with retention of peroxidatic activity. 698 10


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