Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following a brief introduction of cellular response to stimulation comprising leukocyte activation, three major areas are discussed: (1) the neutrophil oxidase; (2) myeloperoxidase (MPO)-dependent oxidative microbicidal reactions; and (3) MPO-independent oxidative reactions. Topics included in section (A) are current views on the activation mechanism, redox composition, structural and topographic organization of the oxidase, and its respiratory products. In section (B), emphasis is placed on recent research on cidal mechanisms of HOCl, including the oxidative biochemistry of active chlorine compounds, identification of sites of lesions in bacteria, and attendant metabolic consequences. In section (C), we review the (bio)chemistry of H2O2 and .OH microbicidal reactions, with particular attention being given to addressing the controversial issue of probe methods to identify .OH radical and critical assessment of the recent proposal that MPO-independent killing arises from site-specific metal-catalyzed Fenton-type chemistry.
Crit Rev Biochem Mol Biol 1989
PMID:Leukocytic oxygen activation and microbicidal oxidative toxins. 254 10

A new tetragonal crystal form of canine myeloperoxidase grown by precipitation with ammonium sulfate is described. The space group is P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions. a = b = 133.0 A, c = 203.6 A, and a single molecule in the asymmetric unit. The crystals diffract to Bragg spacings of 2.5 A and are suitable for a medium-resolution structure determination.
J Mol Biol 1989 Dec 05
PMID:Tetragonal crystals of canine myeloperoxidase suitable for X-ray structural analysis. 255 9

Three crystal forms of canine myeloperoxidase are described. An orthorhombic form in space group P2(1)2(1)2(1) has unit cell dimensions: a = 108.3 A (1 A = 0.1 nm) b = 205.9 A and c = 139.9 A. A trigonal form in space group P3(1)21 or P3(2)21 has unit cell dimensions: a = b = 138.9 A and c = 145.2 A. A monoclinic form in space group C2 has unit cell dimensions: a = 117.2 A, b = 96.9 A, c = 131.4 A and beta = 116.3 degrees. Unusual features in the diffraction patterns of the monoclinic form place restrictions on the molecular packing in the crystal. The proposed model for the molecular packing requires that the myeloperoxidase molecule consist of two identical or near-identical halves. In the intact molecule these halves may be related either by a crystallographic dyad axis or by an approximate dyad axis in which one subunit is translated relative to the other by 3.2 A along the symmetry axis. The trigonal crystal form appears most suitable for high-resolution X-ray structural analysis.
J Mol Biol 1987 Aug 20
PMID:Crystallization and subunit structure of canine myeloperoxidase. 282 90

To examine the effects of acute myocardial ischemia and reperfusion on regional coronary vasodilator (or flow) reserve, peak reactive hyperemic blood flow following a 10 s occlusion was obtained in dogs subjected to circumflex (Cx) coronary artery occlusion for 1 h followed by reperfusion for 1 h. Acute myocardial ischemia resulting from Cx artery occlusion-reperfusion caused an attenuation in peak reactive hyperemic Cx flow (mean +/- S.E., from 215 +/- 29% to 87 +/- 17%, P less than or equal to 0.001). Acetylcholine-induced increase in Cx flow was also significantly (P less than or equal to 0.01) attenuated following Cx occlusion-reperfusion. These alterations were not observed in the left anterior descending (LAD) coronary artery, which was not subjected to occlusion. Pre-treatment of four dogs with indomethacin inhibited prostaglandin release (P less than or equal to 0.01), but did not affect peak reactive hyperemic coronary flow or acetylcholine-induced increase in coronary flow before or after occlusion-reperfusion. Histopathology revealed extensive myocardial neutrophil infiltration in the Cx-supplied region compared to the LAD-supplied region. Myocardial myeloperoxidase activity, an index of neutrophil infiltration, was also increased in the Cx compared to the LAD region (P less than or equal to 0.02). Myocardial neutrophil accumulation and myeloperoxidase activity were similar in the control and indomethacin-treated animals. These observations suggest that acute myocardial ischemia resulting from coronary artery occlusion-reperfusion impairs coronary vasodilator reserve in anesthetized dogs. This impairment, which was not modified by prostaglandin inhibition, may be related to the loss of endothelium-derived relaxing factor and/or decreased microvascular cross-sectional area resulting from capillary plugging by neutrophils.
J Mol Cell Cardiol 1988 Oct
PMID:Reduction in coronary vasodilator reserve following coronary occlusion and reperfusion in anesthetized dog: role of endothelium-derived relaxing factor, myocardial neutrophil infiltration and prostaglandins. 285 Oct 52

Quantitative estimations of the mean areas of cell, nucleus and cytoplasm in polymorphonuclear leucocytes (PMN) were performed by automated image analysis of blood smears from six patients with acute myeloid leukaemia. The PMN were qualitatively separated by a cytochemical staining method into two well-defined subpopulations i.e. myeloperoxidase (MPO)-normal and MPO-deficient PMN. MPO-deficient PMN were characterized by a decreased size of the total cell (P less than 0.01), an increased size of the nucleus (P less than 0.01) and a decreased size of the cytoplasm (P less than 0.01). The resulting highly increased nucleus-to-cytoplasm ratio in this specific PMN subpopulation bears a striking resemblance to cells in malignant tumours. The planimetric results in this study further support the concept that MPO-deficient PMN may be the progeny of leukaemic precursors.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Myeloperoxidase deficient polymorphonuclear leucocytes: computerized planimetric estimations of cellular and nuclear size. 288 56

The oxidation of phenol catalyzed by human myeloperoxidase and horseradish peroxidase resulted in extensive binding of phenol-derived metabolites to boiled rat liver protein. This binding paralleled closely the removal of phenol from the incubations and was inhibited from 83 to 99% by the addition of the antioxidants, ascorbate and glutathione, suggesting that metabolism and binding were occurring via a one-electron oxidation pathway. Metabolic studies employing both human myeloperoxidase and horseradish peroxidase resulted in the identification of 4,4'-biphenol and diphenoquinone as the principal identifiable metabolites. The addition of reduced glutathione to incubations containing horseradish peroxidase resulted in the formation of two conjugate species. These conjugate species were identified by fast atom bombardment mass spectrometry to be glutathione conjugates of diphenoquinone. The major gluthathione conjugate was identified as 3-(glutathion-S-yl)-4,4'-biphenol by NMR spectroscopy. These results suggest that the formation of highly reactive species through the peroxidase-mediated metabolism of phenol and other phenolic compounds could play an important role in the hematopoietic toxicity observed during chronic benzene exposure.
Mol Pharmacol 1986 Dec
PMID:Metabolic activation of phenol by human myeloperoxidase and horseradish peroxidase. 302 15

Polymorphonuclear leukocytes (PMN) or neutrophils have multiple systems available for killing ingested bacteria. Nearly each of these incorporates H2O2 indicating the essential nature of this reactive oxygen intermediate for microbicidal activity. Following ingestion of bacteria by PMN, H2O2 is formed by the respiratory burst which consumes O2 and generates H2O2 from O2 .-. H2O2 is deposited intracellularly near bacteria within phagocytic vacuoles where it can react with the MPO-H2O2-halide system to form toxic hyperchlorous acid (HOCl) and/or possibly singlet oxygen (1O2). H2O2 can also react with O2 .- and/or iron (Fe++) from lactoferrin or bacteria to form the highly toxic hydroxyl radical (.OH). These mechanisms appear important since deficiencies of H2O2 production, myeloperoxidase or lactoferrin frequently increases their owner's susceptibility to infection. In particular, examination of PMN from infection prone patients with chronic granulomatous disease (CGD) most clearly demonstrates the importance of H2O2 in killing of bacteria. CGD PMN lack the capacity to effectively generate H2O2 and subsequently have impaired ability to kill catalase positive (H2O2 producing) but not catalase negative (not H2O2 producing) bacteria. PMN also have catalase and glutathione peroxidase systems in their cytoplasms to protect themselves from the toxicity of H2O2. Finally, while H2O2 is critical for host defense, it can also be released extracellularly and thereby play a significant role in PMN mediated tissue injury.
Mol Cell Biochem 1982 Dec 10
PMID:Hydrogen peroxide mediated killing of bacteria. 629 93

The role of various enzymes and biological molecules on the activation and deactivation of the metabolites of phenol was investigated in vitro. Phenol, the major metabolite of benzene, is metabolized to hydroquinone and catechol. Activation of these metabolites and deactivation of their oxidized forms was assessed by the amount of covalent binding to microsomal protein. [14C]Phenol and NADPH were incubated with hepatic microsomes isolated from phenobarbital-pretreated guinea pigs, and 2.33 nmoles of hydroquinone and 0.12 nmole of catechol were formed per minute per milligram of microsomal protein. Covalent binding of the metabolites to microsomal protein incubated with microsomes isolated from guinea pigs pretreated with phenobarbital was 252 pmoles bound/min/mg; with microsomes from untreated guinea pigs, covalent binding was 146 pmoles bound/min/mg. Covalent binding was inhibited greater than 90% with the addition of N-octylamine, ascorbate, or GSH. The addition of superoxide dismutase inhibited covalent binding with microsomes isolated from phenobarbital-pretreated guinea pigs 35% but did not inhibit it with microsomes isolated from untreated animals. Partially purified guinea pig hepatic DT-diaphorase [NAD(P)H (quinone acceptor) oxidoreductase, EC 1.6.99.2] inhibited covalent binding 70%. This effect was reversed in the presence of dicumarol, a specific inhibitor of DT-diaphorase. DT-diaphorase present in the 10(5) X g supernatant fraction was also active in inhibiting covalent binding but only after the removal of endogenous reduced glutathione. This effect could also be reversed by dicumarol. The addition of diaphorase (NADH:lipoamide oxidoreductase, EC 1.6.4.3) partially purified from Clostridium kluyveri inhibited covalent binding 86%. The addition of hydrogen peroxide and horseradish peroxidase (peroxidase, EC 1.11.17) or myeloperoxidase(s) increased covalent binding 30-fold and 6-fold, respectively. Ascorbate decreased this binding greater than 95%. These results indicate that hydroquinone, catechol, and phenol as well as their oxidized forms can be activated or deactivated by several of the above model systems. These systems may play a role in the myelotoxicity of benzene by modulating covalent binding.
Mol Pharmacol 1984 Jul
PMID:DT-diaphorase and peroxidase influence the covalent binding of the metabolites of phenol, the major metabolite of benzene. 674 27

NADPH oxidase from stimulated guinea pig granulocytes was extracted with deoxycholate. The solubilized enzyme was stable in 20% glycerol. Solubilized enzyme was free of myeloperoxidase activity. The properties of the deoxycholate solubilized enzyme indicated that it is a high molecular weight complex with a flavoprotein, calmodulin and cytochrome b possibly forming part of the complex. Maximum activity was between pH 7.0 and 7.5. The Km value was 15.8 microM for NADPH and 434 microM for NADH indicating that NADPH is the preferential substrate.
Mol Cell Biochem 1983
PMID:The NADPH oxidase of guinea pig polymorphonuclear leucocytes. Properties of the deoxycholate extracted enzyme. 686 30

Acute leukemias containing > 3% myeloperoxidase (MPO)-positive blast cells, as detected cytochemically, are considered to be myelogenous in origin, regardless of the immunophenotypic markers expressed. Conversely, acute leukemias that express only myeloid antigens are also considered to be acute myelogenous leukemia (AML), even in the absence of MPO. These MPO-negative AMLs, designated AML-M0 in the FAB classification, currently require either immunophenotypic or electron microscopic studies for identification. To examine the association of MPO and myeloid antigen expression in AML, particularly at the early stages of myeloid cell differentiation, we have used in situ hybridization (ISH) to evaluate MPO gene expression in myeloid leukemia cell lines and a variety of well-characterized acute leukemias, including six cases of AML-M0. Strong positivity for MPO mRNA was detected in the myeloid leukemia cell line HL-60 and in 22 of 27 AMLs (three AML-M0, four AML-M1, eight AML-M2, five AML-M4, two AML-M5a). No MPO gene expression was detected in three AML-M0, one AML-M5a, one AML-M7, 5 acute lymphoblastic leukemia, the lymphoid cell lines Molt-4 and Namalwa, or in the early myeloid cell lines KG-1 and KG-1a. Ultrastructural studies for MPO activity were performed on four AML-M0; one leukemia showed both gene expression and cytochemical activity, whereas two others contained neither MPO transcripts nor enzyme. Weak MPO gene expression was evident in one AML-M0 that was negative for enzymatic activity by electron microscopy. These studies show MPO gene expression can be detected by ISH in about half of AML-M0, supporting their presumed myelocytic derivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagn Mol Pathol 1995 Sep
PMID:Detection of myeloperoxidase gene expression in minimally differentiated acute myelogenous leukemia (AML-M0) using in situ hybridization. 749 41


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