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)

Oxygen metabolites generated by myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase contribute to microbial killing by phagocytes. To compare the importance of the 2 enzymes for host defense, MPO-deficient (MPO(-/-)) mice and NADPH-oxidase-deficient mice with chronic granulomatous disease (CGD mice) were intraperitoneally infected with 3 different doses of Candida albicans, and their infection severity was analyzed. CGD mice had increased mortality and exhibited increased tissue fungal burden in a dose-dependent manner, whereas normal mice showed no symptoms. Of interest, at the highest dose, the mortality of MPO(-/-) mice was comparable to that of CGD mice, but at the lowest dose, it was the same as that of normal mice. At the middle dose, the number of fungi disseminated into various organs of the MPO(-/-) mice was comparable to that of the CGD mice at day 6 of infection, but it was significantly lower at day 14. These results suggest that MPO and NADPH-oxidase are equally important for early host defense against a large inoculum of Candida.
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PMID:Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans. 1208 36

Mammalian spermatozoa must undergo a preparation period known as capacitation to become capable of fertilizing oocytes. Controlled amounts of reactive oxygen species (ROS), such as superoxide anion (O2.-) and hydrogen peroxide (H2O2) have been shown essential for capacitation and acrosome reaction. The presence of an oxidase in the sperm plasma membrane has been suggested. The objective of the present study was to provide evidence for the production of O2.- by capacitating cryopreserved bovine spermatozoa. Percentages of capacitation and acrosome reaction were determined by the chlortetracycline assay. The effect of several nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors on capacitation was also studied. H2O2 production was determined by the fluorometric assay using the p-hydroxyphenylacetic acid-horseradish peroxidase system. Superoxide dismutase (SOD) activity was determined spectrophotometrically at 480 nm. Heparin-dependent capacitation was inhibited by all NADPH oxidase inhibitors tested (p < 0.05). Significant levels of H2O2 were produced during capacitation with heparin; such production was inhibited by diphenyleneiodonium, one of the NADPH oxidase inhibitors. The addition of catalase to the incubation medium failed to modify the capacitation rate; inhibition was only observed when SOD was present (p < 0.05). Endogenous SOD activity was diminished during heparin-dependent capacitation (p < 0.05). Similar levels of acrosome reaction induced by lysophosphatidylcholine were obtained in both heparin and O2.--dependent capacitation. Overall results suggest the participation of a sperm oxidase in bovine sperm capacitation. H2O2, generated by O2.- dismutation, failed to participate in capacitation, although this ROS may have been able to decrease endogenous SOD activity. Exogenous O2.- promotes physiological capacitation in cryopreserved bovine sperm, thus allowing the acquisition of fertilizing capacity.
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PMID:Participation of superoxide anion in the capacitation of cryopreserved bovine sperm. 1264 29

DNA is damaged in vivo by the Fenton reaction mediated by Fe2+ and cellular reductants such as NADH, which reduce Fe3+ to Fe2+ and allow the recycling of iron. To study the response of Escherichia coli to such cycling, the activities of several enzymes involved in nicotinamide nucleotide metabolism were measured following an H2O2 challenge. NADPH-dependent peroxidase, NADH/NADP+ transhydrogenase, and glucose-6-phosphate dehydrogenase were most strongly induced, increasing 2.5-3-fold. In addition, the cellular ratios of NADPH to NADH increased 6- or 92-fold 15 min after exposure to 0.5 or 5 mm H2O2, respectively. In vitro, NADH was oxidized by Fe3+ up to 16-fold faster than NADPH, despite their identical reduction potentials. To understand this rate difference, the interactions of Fe3+ and Ga3+ with NAD(P)H were examined by 1H, 13C, and 31P NMR spectroscopy. Association with NADH occurred primarily with adenine at N7 and the amino group, but for NADPH, strong metal interactions also occurred at the 2'-phosphate group. Interaction of M3+ (Fe3+ or Ga3+) with the adenine ring would bring it into close proximity to the redox-active nicotinamide ring in the folded form of NAD(P)H, but interaction of M3+ with the 2'-phosphate group would avoid this close contact. In addition, as determined by absorbance spectroscopy, the energy of the charge-transfer species was significantly higher for the Fe3+.NADPH complex than for the Fe3+.NADH complex. We therefore suggest that upon exposure to H2O2 the NADH pool is depleted, and NADPH, which is less reactive with Fe3+, functions as the major nicotinamide nucleotide reductant.
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PMID:Effects of hydrogen peroxide upon nicotinamide nucleotide metabolism in Escherichia coli: changes in enzyme levels and nicotinamide nucleotide pools and studies of the oxidation of NAD(P)H by Fe(III). 1291 9

Pepper, Rollin E. (Michigan State University, East Lansing), and Ralph N. Costilow. Electron transport in Bacillus popilliae. J. Bacteriol. 89:271-276. 1965.-Bacillus popilliae was found to be unique among aerobic microorganisms in that it was deficient in a hydrogen peroxide-scavenging system. Neither catalase nor peroxidase was found. At the same time, a system for producing hydrogen peroxide during oxidation of reduced nicotinamide adenine dinucleotide (NADH(2)) was consistently present in the soluble fraction of extracts of cells from older cultures. Cells harvested from 9-hr cultures did not produce a significant amount of peroxide. The soluble NADH(2) oxidase was apparently a flavoprotein, since it was stimulated by flavin nucleotides, insensitive to cyanide and azide, and inhibited by Atabrine. Also, difference spectra demonstrated the presence of a reducible flavin in the soluble fraction of cell extracts. The particulate fraction of cell extracts was shown by difference spectra to contain cytochrome b(1); the strong inhibition of NADH(2) oxidation by cyanide, azide, and carbon monoxide indicated that a terminal cytochrome oxidase was also present. This system was also flavin-dependent, since it was strongly inhibited by Atabrine. The specific activity of the NADH(2) oxidase in the particulate fraction was lower in extracts of cells from older cultures than in those from exponentially growing cultures. Cytochrome c was not found in extracts of these cells. It is believed that the increased participation of the hydrogen peroxide-generating NADH(2) oxidase in cells of older cultures may be responsible for the rapid loss in cell viability noted in stationary-phase cultures.
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PMID:ELECTRON TRANSPORT IN BACILLUS POPILLIAE. 1425 89

Although para-nonylphenol (NP) is known as an endocrine disruptor, the immunologic effect of NP has been poorly analyzed. We found that NP from 5 to 50 microM caused a dose-dependent stimulatory effect on the generation of reactive oxygen species (ROS) in human blood neutrophils, which was measured by using a chemiluminescence reagent, luminol. Furthermore, ROS-scavenging enzymes such as catalase and superoxide dismutase and antioxidative agents alpha-tocopherol and beta-carotene showed strong preventive effects on NP-induced ROS generation. To analyze the biochemical mechanism of NP-induced ROS generation in human neutrophils, we investigated the effects of different types of metabolic inhibitor for the activation pathways of ROS generation in the cells. Reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase inhibitor, diphenyl iodonium chloride and the myeloperoxidase inhibitor sodium azide (NaN3) showed remarkable inhibitory effects on ROS generation induced by NP, but an inhibitor against mitochondrial respiratory function, potassium cyanide (KCN), did not exhibit significant effect. Furthermore, the phosphatidylinositol-3 (PI3) kinase inhibitor wortmannin and the tyrosine kinase inhibitor protein phosphorylation inhibitor 1 (PP1) caused strong suppression against NP-induced ROS generation. The selective protein kinase C inhibitor Ro-32-0432, p38 MAP kinase inhibitor SB 203580, and ERK MAP kinase inhibitor PD 98059 also showed significant suppressive effects on NP-induced ROS generation. These results suggest that NP causes an enhancing effect on ROS generation in human blood neutrophils through the activation of signal transduction pathways associated with the respiratory burst function in these cells. Additionally, to examine in vivo effects of NP, we also analyzed the effects of NP itself and the synergistic effects of NP and a typical inflammatory agent, opsonized zymosan, on human whole blood including neutrophils.
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PMID:Enhancing effect of the endocrine disruptor para-nonylphenol on the generation of reactive oxygen species in human blood neutrophils. 1506 60

Oxidative stress contributes to the initiation and the development of atherosclerotic plaques and adversely influences myocardial integrity. Statins interfere with oxidation in several ways that may contribute to reducing the atherogenic process. In addition to direct antioxidant effects, statins reduce circulating oxidized low-density lipoproteins (oxLDL) and inhibit their uptake by macrophages. They also reduce circulating markers of oxidation such as F2-isoprostane and nitrotyrosine. Statins inhibit oxidant enzymes activity such as that of reduced nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase and myeloperoxidase and up-regulate the activity of antioxidant enzymes such as catalase and paraoxonase. They reduce endothelial dysfunction mainly by their ability to enhance endothelial nitric oxide bioavailability, which is achieved by several mechanisms. The antioxidant properties of statins extend to organ protection especially the myocardium and the lungs.
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PMID:The antioxidant effects of statins. 1523 21

Mitochondrial failure to generate ATP can be due to damage to their membranes, which leads to release of solutes, e.g., pyridine nucleotides, from the mitochondrial matrix. We developed a highly sensitive fluorescence assay for detecting a pathologic increase in mitochondrial membrane permeability. The assay is based on coupled enzymatic reactions that produce hydrogen peroxide in the presence of the reduced or oxidized form of nicotinamide adenine dinucleotide (NADH/NAD). The hydrogen peroxide is a substrate for horseradish peroxidase that converts Amplex Red into highly fluorescent Resorufin. The assay is able to detect nanomolar levels of pyridine nucleotides in the medium. Calcium additions to isolated rat brain or liver mitochondria incubated in a potassium-based medium with added enzymes caused osmotic swelling, as detected with light scattering, and production of Resorufin, due to release of NADH/NAD. These events were blocked by cyclosporin A (CsA) or Bongkrekic acid (BKA), inhibitors of the mitochondrial permeability transition (MPT). These results indicate that the NADH/NAD release assay is a simple, reliable, and sensitive method for detecting mitochondrial damage and for screening of compounds that protect mitochondria from injury.
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PMID:A fluorescence-based technique for screening compounds that protect against damage to brain mitochondria. 1529 55

Hydrogen peroxide (H(2)O(2)) is found in exhaled breath and is produced by airway epithelia. In addition, H(2)O(2) is a necessary substrate for the airway lactoperoxidase (LPO) anti-infection system. To investigate the source of H(2)O(2) produced by airway epithelia, PCR was used to screen nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in human airway epithelia redifferentiated at the air-liquid interface (ALI) and demonstrated the presence of Duox1 and 2. Western blots of culture extracts indicated strong expression of Duox, and immunohistochemistry of human tracheal sections localized the protein to the apical portion of epithelial cells. Apical H(2)O(2) production was stimulated by 100 microM ATP or 1 microM thapsigargin, but not 100 microM ADP. Diphenyleneiodonium, an NADPH oxidase inhibitor, and dimethylthiourea, a reactive oxygen species scavenger, both inhibited this stimulation. ATP did not stimulate the basolateral H(2)O(2) production by ALI cultures. ATP and thapsigargin increased intracellular Ca(2+) with kinetics similar to increasing H(2)O(2) production, and thus consistent with the expected Ca(2+) sensitivity of Duox. These data suggest that Duox is the major NADPH oxidase expressed in airway epithelia and therefore a contributor of H(2)O(2) production in the airway lumen. In addition, the data suggest that extracellular H(2)O(2) production may be regulated by stimuli that raise intracellular Ca(2+).
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PMID:Regulated hydrogen peroxide production by Duox in human airway epithelial cells. 1567 70

2-Cys peroxiredoxin (Prx) is a novel cellular peroxidase that reduces peroxides in the presence of thioredoxin, thioredoxin reductase, and nicotinamide adenine dinucleotide phosphate (NADPH) and that functions in H(2)O(2)-mediated signal transduction. Recent studies have shown that 2-cys Prx can be inactivated by cysteine overoxidation in conditions of oxidative stress. Therefore, peroxidase activity, rather than the protein level, of 2-cys Prx is the more important measure to predict its cellular function. Here, we introduce a modified activity assay method for mammalian 2-cys Prx based on yeast nonselenium thioredoxin reductase. Yeast thioredoxin reductase is expressed in Escherichia coli cells and purified at high yield (40 mg/L of culture broth) as an active flavoprotein by combined diethyl aminoethyl (DEAE) and phenyl hydrophobic chromatography. The optimal concentrations of yeast thioredoxin and thioredoxin reductase required to achieve maximum mammalian 2-cys Prx activity are 3.0 and 1.5 microM, respectively. This modified assay method is useful for measuring 2-cys Prx activity in cell lysates and can also be adapted for a 96-well plate reader for high-throughput screening of chemical compounds that target 2-cys Prx.
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PMID:Activity assay of mammalian 2-cys peroxiredoxins using yeast thioredoxin reductase system. 1574 41

Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by DNA single-strand breakage, which can be triggered by reactive oxygen and nitrogen species. Activation of this enzyme depletes the intracellular concentration of energetic substrates such as nicotinamide adenine dinucleotide (NAD). Eventually, this process results in cell dysfunction and cell death. PARS inhibitors have successfully shown benefits in several experimental models of ischemia-reperfusion injury, inflammation, and sepsis. In our experimental study, we investigated the role of 3-aminobenzamide (3-AB), a nonspecific PARS inhibitor, in systemic organ damage after burn. Twenty-four Wistar rats were randomly divided into three groups. The sham group (n=8) was exposed to 21 degrees C water, and the burn group (n=8) and the burn-plus-3-AB group (n=8) were exposed to boiling water for 12 s to produce a full-thickness burn of 35-40% of total body surface area. In the burn-plus-3-AB group, 3-AB 10 mg/kg was given intraperitoneally 10 min before thermal injury. Twenty-four hours later, tissue samples were obtained for biochemical analysis from lung, intestine, and kidney. In the burn group, tissue malondialdehyde, myeloperoxidase, and 3-nitrotyrosine levels in all organs were significantly increased compared with the sham group (p<0.05). Pretreatment with 3-AB significantly reduced burn-induced organ damage (p<0.05). These data provide evidence of the relationship between the PARS pathway and lipid peroxidation in systemic organ damage after thermal injury.
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PMID:Poly (adp-ribose) synthetase inhibition reduces oxidative and nitrosative organ damage after thermal injury. 1589 38


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