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)

A microbicidal system, mediated by neutrophil myeloperoxidase, inhibits succinate-dependent respiration in Escherichia coli at rates that correlate with loss of microbial viability. Succinate dehydrogenase, the initial enzyme of the succinate oxidase respiratory pathway, catalyzes the reduction of ubiquinone to ubiquinol, which is reoxidized by terminal oxidase complexes. The steady-state ratio of ubiquinol to total quinone (ubiquinol + ubiquinone) reflects the balance between dehydrogenase-dependent ubiquinone reduction and terminal oxidase-dependent ubiquinol oxidation. Myeloperoxidase had no effect on total quinone content of E. coli but altered the steady-state ratio of ubiquinol to total quinone. The ratio doubled for organisms incubated with the myeloperoxidase system for 10 min, suggesting decreased ubiquinol oxidase activity, which was confirmed by observation of a 50% decrease in oxidation of the ubiquinol analogue 2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinol. Despite inhibition of ubiquinol oxidase, overall succinate oxidase activity remained unchanged, suggesting that succinate dehydrogenase activity was preserved and that the dehydrogenase was rate limiting. Microbial viability was unaffected by early changes in ubiquinol oxidase activity. Longer (60 min) exposure of E. coli to the myeloperoxidase system resulted in only modest further inhibition of the ubiquinol oxidase, but the ubiquinol to total quinone ratio fell to 0%, reflecting complete loss of succinate dehydrogenase activity. Succinate oxidase activity was abolished, and there was extensive loss of microbial viability. Early myeloperoxidase-mediated injury to ubiquinol oxidase appeared to be compensated for by higher steady-state levels of ubiquinol which sustained electron turnover by mass effect. Later myeloperoxidase-mediated injuries eliminated succinate-dependent ubiquinone reduction, through inhibition of succinate dehydrogenase, with loss of succinate oxidase activity, effects which were associated with, although not clearly causal for, microbicidal activity.
 ...
PMID:Myeloperoxidase-mediated inhibition of microbial respiration: damage to Escherichia coli ubiquinol oxidase. 254 43

Myeloperoxidase-oxidase reactions with close to physiological concentrations of thiols and phenols were studied. Cysteine was shown to be a myeloperoxidase-oxidase substrate when catalytic amounts of serotonin were added as cosubstrate. Penicillamine could be substituted for cysteine and acetaminophen could be substituted for serotonin. The properties of these peroxidase-oxidase reactions, e.g. the dependence on substrate and myeloperoxidase concentration, reduced oxygen species, metal ions and pH, were studied. Also, eosinophil, lacto- and horseradish peroxidase could catalyse these reactions.
 ...
PMID:Involvement of cysteine, serotonin and their analogues in peroxidase-oxidase reactions. 254 63

Colonic inflammation was induced in rats by intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of trinitrobenzene sulfonic acid (TNB). Control rats were treated with 0.25 ml of 50% ethanol or with 30 mg of TNB in 0.25 ml of saline. After 24 h, mucosal ulceration and hemorrhage were observed in TNB/ethanol-, 50% ethanol-, and to a lesser extent, in TNB/saline-treated rats. After 1 wk, mucosal damage was completely resolved in the 50% ethanol and TNB/saline-treated rats but the lesions in the TNB/ethanol-treated rats persisted and progressed to a chronic active inflammatory process after 3 wk. Myeloperoxidase activity was significantly elevated in mucosal scrapings from all treatment groups at all time intervals when macroscopic and microscopic mucosal injury was evident. Interleukin-1 was found to be the most sensitive indicator of mucosal inflammation, and its mucosal values correlated with myeloperoxidase activity. Leukotriene B4 was increased in control rats at 1 wk and in TNB/ethanol-treated rats at all time intervals. The maximal increase in leukotriene B4 was observed at 1 wk. Thromboxane B2 generation was reduced while platelet activating factor generation was not increased in TNB/ethanol-treated rats. These results indicate that in this TNB/ethanol model of gut inflammation, myeloperoxidase activity and interleukin-1 are reliable and sensitive indicators of colonic inflammation, and that thromboxane B2 is not involved in the acute lesions, whereas leukotriene B4 appears in the chronic active inflammatory response.
 ...
PMID:Inflammatory mediators of experimental colitis in rats. 254 4

Acute leukemia was diagnosed in 62 adults and children over a recent 13-month period. Using light microscopy, cytochemical profiles, surface markers, and cytogenetics, 25 cases were classified as acute myeloid leukemia (AML) and 32 as acute lymphoblastic leukemia (ALL). The remaining 5 cases of de novo acute leukemia were unclassifiable. The routine cytochemical battery used on these 62 cases included: myeloperoxidase, sudan black B, nonspecific esterase, and periodic acid-Schiff (PAS). Flow markers utilized were: T3, T4, T5, T8, T10, T11, B1, B4, kappa, lambda, Ia, CALLA, Mo1, Mo2, My4, My7, My8, and My9. TdT was performed by immunoperoxidase and ELISA methods. The five unclassified cases were cytochemically negative and expressed no B- or T-cell-specific antigens, or TdT positivity. The morphologic differential diagnosis was between FAB L-2 and M-1. Karyotypic abnormalities involving chromosomes 3 and 7 were suggestive of myeloid origin in 2 of 4 patients studied. Flow cytometry demonstrated My7 on greater than 50% of blasts from two cases. Myeloperoxidase ultracytochemistry showed reaction product in small primary granules of blasts from all 5 cases. Positive cells contained only 1-2 granules/cell profile. The number of positive cells per case was in the range 10-20%. We conclude from this study that ultracytochemistry is very useful in providing definitive diagnosis and accurate subclassification of some AML FAB M-1 cases, particularly when light microscopic cytochemistry, cytogenetics, and flow cytometric markers are noncontributory. We propose to designate these acute "unclassified" leukemias as AML FAB M-1 "microgranular" type.
 ...
PMID:Acute myeloid leukemia, FAB M-1 microgranular variant: a multiparameter study. 254 66

1. Myeloperoxidase is inhibited by various diketones that are recognized arginine reagents. 2. Although arginine residues in the enzyme were modified in both the light and the dark, enzyme inactivation occurred only in the presence of light. 3. Under conditions where diketones caused inactivation of myeloperoxidase, spectral studies indicated marked damage to the haem residues of the enzyme. 4. It was concluded that diketones serve simply as photosensitizers of visible light-induced inactivation of myeloperoxidase. 5. Studies on other haemoproteins indicated the great ease with which the presence of diketones sensitized haem residues for photodestruction.
 ...
PMID:Effect of 2,3-butanedione on human myeloperoxidase. 254 72

Polymorphonuclear leukocytes (PMN) isolated from human blood were exposed to various levels of hydrogen sulfide. The effect on respiratory burst, myeloperoxidase activity, and capacity to phagocytose and kill bacteria were studied. A 1-h exposure of the PMN to 1 mM sulfide did not decrease their myeloperoxidase activity or their capacity to initiate a respiratory burst. Actually the products of the respiratory burst rapidly oxidized sulfide. The phagocytosis and killing of bacteria in the presence of 1 mM sulfide was only decreased to a minor extent. Myeloperoxidase in cell extract was, however, almost completely inhibited by 1 microM sulfide. These results indicate that hydrogen sulfide does not easily permeate PMN. PMN may be able to function in infected sites with high sulfide levels such as in the gingival pockets of periodontal disease. In the oxygenated areas of these sites the PMN may actually help in the detoxification of sulfide.
 ...
PMID:Activity of polymorphonuclear leukocytes in the presence of sulfide. 254 20

Myeloperoxidase (MPO), present in the azurophilic granules of human polymorphonuclear neutrophils, is important in the oxygen-dependent microbicidal activity of neutrophils. The purpose of our study was to investigate the therapeutic potency of the MPO preparations. This paper is to present our primary work on MPO isolation and its microbicidal activity assay. White blood cells, isolated freshly from normal donors, were lysed with cetyltrimehylammonium bromide to liberate myeloperoxidase. The enzyme preparation was partially purified by 50% (NH4)2SO4 precipitation followed by 65% (NH4)2SO4 precipitation. A hundred million leukocytes yielded 1.03 mg protein of the MPO preparation with the RZ of 0.31. The specific activity of the MPO preparation was about 29.25 u/mg. When 0.672 units of the MPO preparation were incubated with about 10(7) clinical isolates of Candida albicans in the presence of 0.2 mmol/L H2O2 and 0.14 mol/L NaCl. It was detected that 95.58 +/- 0.64% of the organisms were killed in the methylene blue staining system.
 ...
PMID:[In vitro assessment of candidacidal activity of human leukocyte myeloperoxidase preparation]. 255 12

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.
 ...
PMID:Metabolic activation of eugenol by myeloperoxidase and polymorphonuclear leukocytes. 256 21

Myeloperoxidase (MPO) is a lysosomal enzyme present in the azurophilic granules of human neutrophils and monocytes and is important for optimal oxygen-dependent killing of microorganisms. The native molecule is a heterodimer composed of a pair of heavy-light protomers, each containing a 59-kDa and 13.5-kDa subunit. The intracellular processing during biosynthesis of MPO was examined in the human promyelocytic cell line HL-60. Endoglycosidase H and F digestion of immunoprecipitated pro-MPO demonstrated the presence of five N-linked--high-mannose oligosaccharide side chains and no complex mannose units. Incorporation of the threonine analogue beta-hydroxynorvaline produced species approximately 2.5 kDa and approximately 5 kDa smaller than the fully glycosylated pro-MPO, suggesting that two of the glycans were in the asparagine-X-threonine tripeptide sequence. Processing of pro-MPO occurred very rapidly, within approximately five minutes, and was best identified using glucosidase inhibitors. The presence of such inhibitors resulted in synthesis of a 92-kDa glycoprotein rather than the usually identified 89-kDa peptide. Swainsonine, a Golgi mannosidase inhibitor, did not alter the size of the earliest synthesized protein, suggesting that pro-MPO exited the endoplasmic reticulum or cis-Golgi proximal to the site of mannosidases. Intracellular transport and proteolytic maturation of MPO was retarded by weak bases (NH4Cl, chloroquine) or monensin at concentrations shown to raise intralysosomal pH. However, these agents did not qualitatively alter transport nor increase secretion. Thus, although MPO biosynthesis resembled that of other lysosomal enzymes, significant differences exist, including only limited oligosaccharide processing and intracellular transport and proteolytic maturation of pro-MPO that was only retarded by alkalinizing lysosomes without affecting the products or the fraction of pro-MPO secreted. Characterization of the determinants for targeting and of the regulatory factors in processing lysosomal enzymes in myeloid cells will provide insight into the molecular mechanisms underlying common disorders such as myeloperoxidase deficiency.
 ...
PMID:Posttranslational processing of a human myeloid lysosomal protein, myeloperoxidase. 282 May 30

An in vitro model system was used to define the mechanism of interaction between human neutrophils and lymphocytes. Blood mononuclear leukocytes were exposed to purified neutrophils in the presence of a neutrophil-activating agent (phorbol ester, lectin, or opsonized particle). The treated mononuclear cells displayed a marked decrease in both natural killer activity and mitogen-dependent DNA synthesis, but no change in viability. This functional suppression was dependent on neutrophil number, stimulus concentration, and duration of exposure. Lymphocytes were protected by addition of catalase, but not superoxide dismutase. Neutrophils defective in oxidative metabolism (chronic granulomatous disease) failed to suppress lymphocyte function unless an H2O2-generating system, glucose oxidase plus glucose, was added. The patients' neutrophils provided a factor, possibly myeloperoxidase, which interacted with the glucose oxidase system. The immunosuppressive effect of normal neutrophils was diminished when chloride was omitted from the cultures and was enhanced when chloride was replaced by iodide. Myeloperoxidase-deficient neutrophils were partially defective in suppressing lymphocytes and this was corrected by addition of purified myeloperoxidase. Paradoxically, azide caused enhancement of suppression that depended on the neutrophil oxidative burst, but not on myeloperoxidase and was mediated at least in part by an effect of azide on the target mononuclear leukocytes. These data indicate that suppression of lymphocyte function by activated neutrophils is mediated by the secretion of myeloperoxidase and H2O2 that react with halides to form immunosuppressive products. Moreover, the mononuclear leukocytes contain an azide-sensitive factor, probably catalase, which provides partial protection against injury by neutrophil products. These dynamic interactions may be important local determinants of the immune response.
 ...
PMID:Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system. 282 Nov 14


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