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)

Salicylhydroxamic acid inhibited the luminol-dependent chemiluminescence of human neutrophils stimulated by phorbol 12-myristate 13-acetate or the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). This compound had no inhibitory effect on the kinetics of O2.- generation or O2 uptake during the respiratory burst, but inhibited both the peroxidative activity of purified myeloperoxidase and the chemiluminescence generated by a cell-free myeloperoxidase/H2O2 system. The concentration of salicylhydroxamic acid necessary for complete inhibition of myeloperoxidase activity was 30-50 microM (I50 values of 3-5 microM) compared with the non-specific inhibitor NaN3, which exhibited maximal inhibition at 100-200 microM (I50 values of 30-50 microM). Whereas taurine inhibited the luminol chemiluminescence of an H2O2/HOC1 system by HOC1 scavenging, this compound had little effect on myeloperoxidase/H2O2-dependent luminol chemiluminescence; in contrast, 10 microM-salicylhydroxamic acid did not quench HOC1 significantly but greatly diminished myeloperoxidase/H2O2-dependent luminol chemiluminescence, indicating that its effects on myeloperoxidase chemiluminescence were largely due to peroxidase inhibition rather than non-specific HOC1 scavenging. Salicylhydroxamic acid prevented the formation of myeloperoxidase Compound II, but only at low H2O2 concentrations, suggesting that it may compete for the H2O2-binding site on the enzyme. These data suggest that salicylhydroxamic acid may be used as a potent inhibitor to delineate the function of myeloperoxidase in neutrophil-mediated inflammatory events.
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PMID:Inhibition of myeloperoxidase by salicylhydroxamic acid. 254 61

Effects of temperature on the morphological changes and degranulation were studied in stimulated neutrophils. Neutrophils were stimulated by formyl-methionyl-leucyl-phenylalanine (FMLP) and cytochalasin B at 4 degrees C, 20 degrees C and 37 degrees C, and they were processed for electron microscopy and biochemical assays of myeloperoxidase (MPO) activity. When neutrophils were stimulated at 4 degrees C, they did not show apparent morphological changes nor release MPO activity. In the cells stimulated at 20 degrees C, there were many cytoplasmic vacuoles, localization of MPO-positive granules adjacent to the cell membrane and around the vacuoles, MPO-positive materials in the cavity of the vacuoles, and slightly decreased numbers of granules. They released moderate amounts of MPO activity. The neutrophils at 37 degrees C showed formation of small vacuoles and canaliculi and a marked decrease in the number of MPO-positive granules indicative of degranulation, and they released increased amounts of MPO activity. There were MPO-positive materials on the membrane and in the cavity of the vacuoles. Ruthenium red staining showed that the vacuoles were formed open outside the cell. These results indicate that the vacuolar systems are involved in degranulation in stimulated neutrophils and that their formation is dependent on temperature.
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PMID:Temperature-dependent formation of vacuolar and canalicular systems in association with degranulation in stimulated neutrophils. 254 93

Both the chemotactic peptide formylmethionyl-leucyl-phenylalanine (FMLP) and the calcium ionophore ionomycin induced a metabolic response in normal neutrophils. However, the presence of azide, a potent inhibitor of the hydrogen peroxide-consuming enzymes catalase and myeloperoxidase, was required to detect any release of hydrogen peroxide induced by ionomycin. In differentiated HL-60 cells, only FMLP stimulation was associated with any notable metabolic activation. The response to FMLP proceeds with a rate and time course similar to that seen in normal cells. The use of ionomycin as a stimulating agent did not result in any detectable activation of the system that generates reactive oxygen metabolites, even if azide was present in the measuring system. Raising the concentration of cytoplasmic free Ca2+ is therefore not sufficient to activate the system responsible for the generation of reactive oxygen metabolites in HL-60 cells. However, preincubation with ionomycin primed HL-60 cells to an increased response during stimulation with the chemotactic peptide FMLP and the phorbol ester PMA. Since HL-60 cells lack specific granules but have an intact ligand-receptor coupling mechanism, a role for the subcellular granule is proposed, in the generation of reactive oxygen species in normal granulocytes, and analysis of the data presented leads to two conclusions: 1) FMLP, which acts through cells surface receptors, causes the cells to produce oxygen radicals, which to a large extent are released from the cells, a process that is not dependent on the specific granule content of the cells, whereas 2) ionomycin, which bypasses cell-surface receptors, is also capable of stimulating an oxygen-radical formation that is granule dependent and retained inside the cells. Furthermore, the results suggest that an increase in intracellular Ca2+ is not sufficient to initiate activation of the plasma membrane-bound system that generates reactive oxygen metabolites, but the results support a role for Ca2+ in the priming event.
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PMID:The calcium ionophore ionomycin can prime, but not activate, the reactive oxygen generating system in differentiated HL-60 cells. 254 23

Neutrophil elastase and myeloperoxidase probably play an important role in the development of pulmonary emphysema. We have analyzed drugs from the major classes of agents that alter neutrophil function to determine if there are drugs in use today that can reduce the load of neutrophil elastase or myeloperoxidase in the lungs of smokers. Eleven representative drugs were tested for their ability to inhibit chemotaxis and degranulation. None of the drugs inhibited chemotaxis in a dose-response fashion at concentrations achievable in human plasma. Sulfinpyrazone, phenylbutazone, and auranofin completely inhibited the release of azurophilic granules (myeloperoxidase) and tertiary granules (beta-D-glucuronidase) when formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) was used as the stimulant, and inhibited azurophilic granule release by 69%, 19%, and 64% respectively, but not tertiary granule release when macrophage-conditioned media was used as the stimulus. In conclusion, none of the drugs tested are inhibitors of chemotaxis; however, three are excellent inhibitors of azurophilic granule enzyme release. Of these three, sulfinpyrazone, a drug that is not currently used clinically for its antiinflammatory effects, is the least toxic and should be considered as a potential drug to reduce the elastase and myeloperoxidase load in the lungs of smokers who are developing emphysema.
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PMID:Search for drugs that may reduce the load of neutrophil azurophilic granule enzymes in the lungs of patients with emphysema. 254 34

Interleukin 6 (IL-6), a 26-kDa inducible protein, is a cytokine with multiple biological activities. This paper reports on the regulatory role of rIL-6 on the function of human polymorphonuclear and mononuclear leukocytes, a property not described previously. rIL-6 by itself did not exhibit any chemotactic activity and it could not activate these cells for an oxidative burst response. Preincubation of both cell types with rIL-6 at concentrations of 5 and 50 ng/ml primed the cells for enhanced generation of oxygen radicals following stimulation with the chemotactic peptide f-Met-Leu-Phe or the phorbol ester PMA. The enhancement of the oxidative burst response occurred both at the level of superoxide anion generation, an early step in the activation pathway, and at the level of the hydrogen peroxide-myeloperoxidase mediated response, a later step in the oxidative burst pathway. The priming ability was abolished by heat treatment of rIL-6 at 100 degrees C but not at 70 degrees C. Stimulation of B cell growth and immunoglobulin production combined with enhancement of oxidative burst response of phagocytic cells by IL-6 provide an effective mechanism of fighting against invading micro-organisms.
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PMID:Interleukin 6 primes human neutrophil and monocyte oxidative burst response. 254 55

alpha-Kallikrein was prepared using an improved purification protocol (Burger, D., Schleuning, W.-D. and Schapira, M. (1986) J. Biol. Chem. 261, 324-327) and was employed to reevaluate our previous observations indicating that kallikrein activates blood neutrophils by a mechanism requiring an uncleaved Mr 52,000 NH2-terminal heavy chain. Cellular activation was evaluated by measuring neutrophil aggregation, release of both vitamin B12 binding capacity and myeloperoxidase, and generation of superoxide anion. Whereas all these indicators were evoked by exposing neutrophils to f-Met-Leu-Phe, phorbol myristate acetate, zymosan activated serum, or the calcium ionophore A 23187, we show here that neutrophils incubated with alpha-kallikrein remained unactivated. Moreover, we demonstrate that this lack of activation is accompanied by an inability of neutrophils to specifically bind alpha-kallikrein.
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PMID:Studies on the human plasma kallikrein-kinin system: alpha-kallikrein does not directly activate blood neutrophils. 255 Oct 61

The bioluminescent oxygen metabolite indicator protein pholasin was characterized with respect to the type and location of reactive oxygen metabolites detected in suspensions of stimulated human neutrophils. Whereas pholasin detected reactive oxygen metabolites from neutrophil suspensions stimulated with soluble agents, particulate stimulants were apparently not effective triggering agents for pholasin-dependent neutrophil chemiluminescence. Neutrophils stimulated with fMet-Leu-Phe (1 to 100 nmol/l) showed maximum pholasin-dependent chemiluminescence 45 to 60 s after stimulation. The time of maximum chemiluminescence was virtually independent of fMet-Leu-Phe concentration. In contrast, the time to reach maximum light emission increased from 60 s with 100 nmol/l phorbol ester to 295 s with 1 nmol/l phorbol ester. Significant inhibition of stimulated chemiluminescence was caused by both superoxide dismutase (20 micrograms/ml, 80% inhibition) and reduction of the oxygen concentration in the incubation medium to less than 0.5 mumol/l (95% inhibition). In contrast, the myeloperoxidase inhibitor sodium azide (0.1 mmol/l) afforded only 50% inhibition of the pholasin-dependent neutrophil chemiluminescence. Our results show that pholasin detects superoxide radicals released from cells stimulated by soluble stimulants but not intracellular oxidative activity elicited by particulate stimulants.
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PMID:Pholasin chemiluminescence detects mostly superoxide anion released from activated human neutrophils. 255 Nov 31

The chemotactic activity of elastin-derived peptides (EP) for human polymorphonuclear leukocytes (PMNL) was investigated using the under agarose method. The EP were produced by digesting the bovine ligament elastin with porcine pancreatic elastase. Thus prepared digest had weak chemotactic activity for PMNL. The mean chemotactic index for all tested EP concentrations did not exceed 1.30 and was lower than that obtained with zymosan-activated serum (ZAS, n-formyl-methionyl-leucyl-phenylalanine (FMLP) 2.2 +/- 0.40, 3.1 +/- 0.32, (n = 10) respectively. However, EP (50 micrograms) after injection to the mouse pleural cavity induced PMNL influx. The mean PMNL number found in this cavity was 0.09 +/- 0.03 x 10(6) for PBS and 0.18 +/- 0.03 +/- 10(6) for EP injection (p less than 0.01 n = 6). Human PMNL during 60 min incubation with EP (1 to 10 micrograms/ml) or with EP and cytochalasin B (CB 4.8 micrograms/ml) released myeloperoxidase and low amounts of hydrogen peroxide. At 1 micrograms/ml and in presence of CB elastin digest was nearly as active in myeloperoxidase release as FMLP (300 ng/ml). The values reached 17.1 +/- 2.5 and 19.7 +/- 2.1% of the total activity of whole cell lysate, respectively. The obtained results suggest that EP produced in vivo in the site of inflammation could modulate to some extent its course by enhancing PMNL influx and their activation. It seems that such mechanism of enhancement of the inflammatory response may occur in the lungs which are rich in elastin fibers.
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PMID:Chemotactic activity of elastin-derived peptides for human polymorphonuclear leukocytes and their effect on hydrogen peroxide and myeloperoxidase release. 256 30

The effects of 5-aminosalicylic acid (5-ASA), 4-ASA, N-acetyl-5-ASA, and sulfapyridine on mucosal permeability were determined in an experimental model of acute ileitis. In addition, the antiinflammatory drug dapsone was tested. The distal 10 cm of rat ileum was perfused with formyl-methionyl-leucyl-phenylalanine (FMLP) (10(-5) M), a bacterial peptide that activates and attracts neutrophils. Changes in mucosal permeability were assessed using the blood-to-lumen clearance of 51Cr-ethylene-diamineacetate. Luminal FMLP increased 51Cr-labeled ethylenediamineacetate clearance twofold and fourfold in the first and second hour, respectively. Addition of 5-ASA (10 mM), 4-ASA (10 mM), or dapsone (4 mM) to the luminal perfusate after 60 min of FMLP perfusion greatly attenuated the increased mucosal permeability observed after 120 min of FMLP perfusion. Neither N-acetyl-5-ASA (10 mM) nor sulfapyridine (5 mM) had an effect on the FMLP-induced increase in mucosal permeability. We characterized the inhibitory effect of these drugs on the catalytic activity of myeloperoxidase and tested their ability to scavenge hypochlorous acid in vitro. 5-Aminosalicylic acid, 4-ASA, and dapsone demonstrated a powerful inhibitory effect on the catalytic activity of myeloperoxidase, whereas all drugs were equally effective in scavenging HOCl. In additional in vitro experiments we were unable to demonstrate an inhibitory effect of either of the drugs on the catalytic activity of neutrophilic elastase. Our results indicate that inhibition of neutrophilic myeloperoxidase may be an important mechanism by which 5-ASA, 4-ASA, and dapsone attenuate FMLP-induced mucosal injury.
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PMID:Sulfasalazine metabolites and dapsone attenuate formyl-methionyl-leucyl-phenylalanine-induced mucosal injury in rat ileum. 259 Feb 87

Surface enhanced Raman scattering (SERS) of some enzymes (alkaline phosphatase, horseradish peroxidase and lactoperoxidase) and some amino acids (tryptophan, tyrosine and phenylalanine) on silver electrodes has been studied. The spectral band intensities of certain amino acids and amino acid residues were determined by their orientation on the surface and depended on the electrode potential (E).
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PMID:Structure-potential dependence of adsorbed enzymes and amino acids revealed by the surface enhanced Raman effect. 275 91


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