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

1. Cypridina luciferin analogues, 2-methyl-6-(p-methoxyphenyl)-3,7- dihydroimidazo[1,2-a]pyrazin-3-one (MCLD) and 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2-a]pyrazin-3-one(CLA ), react with O2- or 1O2 to emit light in visible region. Such chemiluminescences were used for the detection of O2- or 1O2 in activated leukocyte systems and myeloperoxidase (granulocyte-extract) + Br- + H2O2 systems in vitro. 2. The mechanisms of MCLA (CLA)-dependent luminescence is described in detail. Superoxide generated from sinusoidal cells in acute ethanol intoxication of rats was detected by MCLA-dependent luminescence from the surface of perfused rat liver (organ luminescence). 3. Furthermore, with alive animals, O2- generated in the lung of rats with necrotized pancreatitis and that in the stomach of rats after ischemia/reperfusion were detected by their organ luminescences.
Cell Mol Neurobiol 1998 Dec
PMID:Detection of active oxygen species in biological systems. 987 66

We examined the hypothesis that superoxide mediates infiltration of neutrophils to the airways through nuclear factor (NF)-kappaB and interleukin-8 (IL-8) after acute exposure to cigarette smoke (CS) in vivo. Male Hartley strain guinea pigs were exposed to air or 20 puffs of CS and killed 5 h after the exposure. The differential cell count of bronchoalveolar lavage fluid and specific myeloperoxidase enzyme assay demonstrated that acute exposure to CS caused neutrophil accumulation to the airways and parenchyma, respectively. Acute exposure to CS increased DNA-binding activity of NF-kappaB in the lung. Acute exposure to CS also increased IL-8 messenger RNA (mRNA) expression in the lung. Pretreatment of guinea pigs with recombinant human superoxide dismutase (rhSOD) aerosols reduced the CS-induced neutrophil accumulation to the airways. Both activation of NF-kappaB and increased IL-8 mRNA expression were also inhibited by the pretreatment of rhSOD aerosols. Strong immunoreactivities for p65 and p50 were detected in the nuclei of alveolar macrophages after acute exposure to CS. The signal for IL-8 mRNA expression was demonstrated in the alveolar space after acute exposure to CS. Neither significant immunoreactivities for p65 and p50 nor IL-8 mRNA signals were observed in airway epithelium. These observations suggest that acute exposure to CS initiates superoxide-dependent mechanism that, through NF-kappaB activation and IL-8 mRNA expression, produces infiltration of neutrophils to the airways in vivo. It was also suggested that the alveolar macrophage is one potential source of NF-kappaB activation and IL-8 mRNA expression after acute exposure to CS.
Am J Respir Cell Mol Biol 1999 Feb
PMID:Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-kappaB activation and IL-8 mRNA expression in guinea pigs in vivo. 992 9

This study was designed to test the effects of polymorphonuclear leukocytes (PMNs) in the presence and absence of a P-selectin blocker, mocarhagin, in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Control rat hearts not subjected to ischemia were perfused without blood cells for 80 min. Additional control rat hearts were perfused with 100 x 10(6) PMNs in the presence and absence of 0.2 microgram/ml mocarhagin over a 5-min perfusion followed by a 45-min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 min of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of PMNs. I/R hearts perfused with PMNs exhibited decreases of 50-60% in all measurements of cardiac function (P < 0.001). These PMN perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selection expression on the coronary microvascular endothelium. All cardiodynamic effects as well as MPO accumulation and PMN infiltration were attenuated markedly by the metalloproteinase, mocarhagin, which inhibits P-selectin-mediated cell adhesion by cleaving its high-affinity receptor, PSGL-1, present on neutrophils. These results provide evidence that neutrophils provoke post-reperfusion cardiac dysfunction, and that this may be largely due to P-selectin-induced adherence of neutrophils to the endothelium.
J Mol Cell Cardiol 1998 Dec
PMID:Effects of a metalloproteinase that truncates P-selectin glycoprotein ligand on neutrophil-induced cardiac dysfunction in ischemia/reperfusion. 999 May 28

Adhesion molecules are key molecules for inflammatory cardiovascular diseases and are known to be up-regulated by inflammatory cytokines. However, the role of adhesion molecules in the cytokine-induced myocardial dysfunction in vivo remains unclear. This role was examined in our novel canine model, in which chronic treatment of the heart with IL-1 beta-bound microspheres (MS), but not control MS, causes sustained myocardial dysfunction in vivo. The expression of P-selectin (mRNA and immunoreactivity) was more prominent in the IL-1 beta group than in the control group (treated with control MS alone) after MS injection. The extent of neutrophil infiltration and myocardial myeloperoxidase (MPO) activity were significantly increased in the IL-1 beta group (P < 0.01). Pre-treatment with SLeX-OS (a novel oligosaccharide analog of sialyl LewisX) or PB1.3 (a monoclonal antibody to P-selectin) prevented the myocardial dysfunction and significantly suppressed the neutrophil infiltration and the increase in myocardial MPO activity induced by IL-1 beta (P < 0.01 each). These results indicate that adhesion molecules play an important role in the pathogenesis of the cytokine-induced sustained myocardial dysfunction in dogs in vivo.
J Mol Cell Cardiol 1998 Dec
PMID:Inhibition of adhesion molecules markedly ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo. 999 May 35

1. The ability of carnosine and carnosine-related compounds (CRCs) to interact with several free oxygen radicals is analyzed. 2. Carnosine, the CRCs (imidazole, histidine, anserine), and ergothioneine were found to be equally efficient in singlet oxygen quenching. During generation of hydroxyl radicals from hydrogen peroxide in the Fenton reaction, carnosine was found to be more effective than the CRCs tested. 3. By measuring the chemiluminescence produced by carnosine and CRCs in rabbit leukocytes in the presence of luminol or lucigenin, we conclude that carnosine and other CRCs play a stimulating role in superoxide oxygen production while suppressing the myeloperoxidase system. 4. ADP-induced aggregation of human platelets is slightly stimulated by carnosine but is inhibited by acetylanserine. 5. The following rank order of efficiency of CRCs was demonstrated while measuring the oxidation of human serum lipoproteins: acetylcarnosine < acetylanserine < homocarnosine = ophidine < carnosine < anserine. 6. The results obtained demonstrate that metabolic transformation of carnosine into CRCs in tissues may play an important role in regulating the native antioxidant status of the organism.
Cell Mol Neurobiol 1999 Feb
PMID:Metabolic transformation of neuropeptide carnosine modifies its biological activity. 1007 75

Lipopolysaccharide (LPS) is a key mediator of multiple organ injury observed in septic shock. The mechanisms responsible for LPS-induced multiple organ injury remain obscure. In the present study, we tested the hypothesis that the LPS-induced injury occurs through activation of the transcription factor, nuclear factor-kappaB (NF-kappaB). We examined the effects of inhibiting NF-kappaB activation in vivo in the rat on LPS-induced: 1) gene and protein expression of the cytokine-inducible neutrophil chemoattractant (CINC) and intercellular adhesion molecule-1 (ICAM-1); b) neutrophil influx into lungs, heart, and liver; and c) increase in microvascular permeability induced by LPS in these organs. LPS (8 mg/kg, i.v.) challenge of rats activated NF-kappaB and induced CINC and ICAM-1 mRNA and protein expression. Pretreatment of rats with pyrrolidine dithiocarbamate (50, 100, and 200 mg/kg, i.p.), an inhibitor of NF-kappaB activation, prevented LPS-induced I-kappaBalpha degradation and the resultant NF-kappaB activation and inhibited, in a dose-related manner, the LPS-induced CINC and ICAM-1 mRNA and protein expression. Pyrrolidine dithiocarbamate also markedly reduced the LPS-induced tissue myeloperoxidase activity (an indicator of tissue neutrophil retention) and the LPS-induced increase in microvascular permeability in these organs. These results demonstrate that NF-kappaB activation is an important in vivo mechanism mediating LPS-induced CINC and ICAM-1 expression, as well as neutrophil recruitment, and the subsequent organ injury. Thus, inhibition of NF-kappaB activation may be an important strategy for the treatment of sepsis-induced multiple organ injury.
Mol Pharmacol 1999 Apr
PMID:Pyrrolidine dithiocarbamate prevents I-kappaB degradation and reduces microvascular injury induced by lipopolysaccharide in multiple organs. 1010 Oct 23

Polymorphonuclear leukocytes (PMN) release gelatinase B in response to variable stimuli. Gelatinase B degrades basement membrane components in vitro, and inhibition of matrix metalloproteinase activity blunts PMN migration through a prototype basement membrane (Matrigel) and amnionic membranes. Accordingly, it has been speculated that gelatinase B is necessary for PMN emigration. To test this hypothesis we induced acute inflammation in the lungs, peritoneum, and skin in mice with a null mutation of the gelatinase B gene (gelatinase B-/-) and littermate controls (gelatinase B+/+). At 3, 6, 12, and 24 h after intratracheal instillation of LPS, the emigration of PMN in the lung, as determined by PMN in bronchoalveolar lavage fluid, was similar in gelatinase B-/- and gelatinase B+/+ mice. The number of PMN in the peritoneal cavity 4 h after thioglycollate-induced peritonitis was also comparable in gelatinase B-/- and gelatinase B+/+ mice. At 4 h after an intradermal injection of interleukin-8, numerous PMN were present extravascularly in the dermis in both gelatinase B-/- and gelatinase B+/+ mice and the myeloperoxidase activities of the skin at the injection sites were indistinguishable between the two types of mice. PMN from gelatinase B-/- mice migrated through Matrigel in response to zymosan-activated serum with the same efficiency as did PMN from gelatinase B+/+ mice. In vitro, gelatinase B-/- PMN killed Staphylococcus aureus and Klebsiella pneumoniae as effectively as did PMN from gelatinase B+/+ mice. These findings indicate that gelatinase B is not required for PMN emigration, and suggest that the antibacterial function of PMN is preserved despite gelatinase B deficiency.
Am J Respir Cell Mol Biol 1999 Jun
PMID:Neutrophil emigration in the lungs, peritoneum, and skin does not require gelatinase B. 1034 Sep 50

Although the role of adenosine deaminase (ADA), adenylate deaminase (AMP-DA), purine nucleoside phosphorylase (PNP) is well documented in gastric and intestinal carcinoma, their role in inflammatory bowel diseases remains unknown. In the present study, we investigated the profile of these enzymes in blood and intestinal tissues during colitis. Colitis induced in Wistar rats by acetic acid was monitored by a marker enzyme myeloperoxidase (MPO). The tissue levels of MPO increased on 1, 2, 5 and 6 days post-administration (PA) of acetic acid and declined to the control levels by day 7 PA. In parallel the blood levels of ADA and AMP-DA decreased on days 1, 2 and 5 without any significant change on days 6 and 7 PA. Similar observations were recorded for these enzymes in the cytosolic extracts of colonic tissue specimens. In contrast, PNP remained unaltered in both blood and tissue samples. These findings suggest an inverse-relationship between inflammation and purine deaminases in both blood and tissues.
Mol Cell Biochem 1999 Apr
PMID:Studies on purine enzymes in experimental colitis. 1039 Nov 19

Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associated with an increased risk of secondary acute myelogenous leukemia. The mechanisms for the extremely high susceptibility of myeloid stem cells to the leukemogenic effects of etoposide have not been elucidated. We propose a mechanism to account for the etoposide-induced secondary acute myelogenous leukemia and nutritional strategies to prevent this complication of etoposide therapy. We hypothesize that etoposide phenoxyl radicals (etoposide-O(.)) formed from etoposide by myeloperoxidase are responsible for its genotoxic effects in bone marrow progenitor cells, which contain constitutively high myeloperoxidase activity. Here, we used purified human myeloperoxidase, as well as human leukemia HL60 cells with high myeloperoxidase activity and provide evidence of the following. 1) Etoposide undergoes one-electron oxidation to etoposide-O(.) catalyzed by both purified myeloperoxidase and myeloperoxidase activity in HL60 cells; formation of etoposide-O(.)radicals is completely blocked by myeloperoxidase inhibitors, cyanide and azide. 2) Intracellular reductants, GSH and protein sulfhydryls (but not phospholipids), are involved in myeloperoxidase-catalyzed etoposide redox-cycling that oxidizes endogenous thiols; pretreatment of HL60 cells with a maleimide thiol reagent, ThioGlo1, prevents redox-cycling of etoposide-O(.) radicals and permits their direct electron paramagnetic resonance detection in cell homogenates. VP-16 redox-cycling by purified myeloperoxidase (in the presence of GSH) or by myeloperoxidase activity in HL60 cells is accompanied by generation of thiyl radicals, GS(.), determined by HPLC assay of 5, 5-dimethyl-1-pyrroline glytathionyl N-oxide glytathionyl nitrone adducts. 3) Ascorbate directly reduces etoposide-O(.), thus competitively inhibiting etoposide-O(.)-induced thiol oxidation. Ascorbate also diminishes etoposide-induced topo II-DNA complex formation in myeloperoxidase-rich HL60 cells (but not in HL60 cells with myeloperoxidase activity depleted by pretreatment with succinyl acetone). 4) A vitamin E homolog, 2,2,5,7, 8-pentamethyl-6-hydroxychromane, a hindered phenolic compound whose phenoxyl radicals do not oxidize endogenous thiols, effectively competes with etoposide as a substrate for myeloperoxidase, thus preventing etoposide-O(.)-induced redox-cycling. We conclude that nutritional antioxidant strategies can be targeted at minimizing etoposide conversion to etoposide-O(.), thus minimizing the genotoxic effects of the radicals in bone marrow myelogenous progenitor cells, i.e., chemoprevention of etoposide-induced acute myelogenous leukemia.
Mol Pharmacol 1999 Sep
PMID:Mechanism-based chemopreventive strategies against etoposide-induced acute myeloid leukemia: free radical/antioxidant approach. 1046 37

Background: Expression of the myeloperoxidase (MPO) gene is specific for myeloid precursors and their leukemic counterparts. Unlike the enzyme, MPO mRNA is found only in early myeloid precursors; this makes MPO mRNA a good marker for myeloid lineage of leukemic blasts. A reverse transcriptase-polymerase chain reaction (RT-PCR) method for MPO mRNA detection was developed and used in the diagnosis of acute myelogenous leukemia (AML). In this study, we investigated the use of MPO mRNA for early detection of circulating blasts in patients with AML during and after chemotherapy. Methods and Results: MPO mRNA detection by RT-PCR was performed on cellular material from archival smears of preipheral blood (PB) and bone marrow aspirate from 16 patients previously diagnosed with AML, types MO-M5. MPO mRNA findings were correlated with morphology and flow-cytometric data. A group of six patients diagnosed with adult de novo acute lymphoblastic leukemia served as a negative patient control group for this retrospective study. MPO mRNA findings in PB appear to follow two patterns in patients with complete remission: (1) sustained positivity throughout the clinical course, correlated with relapse; and (2) initial positivity followed by sustained negativity, correlated with long complete remissions. For the only patient in this study found in partial remission, MP mRNA positivity in PB was seen throughout the clinical course. No MPO mRNA positivity was detected in the PB of acute lymphoblastic leukemia cases. Conclusions: A highly sensitive method for detection of MPO mRNA, such as RT-PCR, is useful in monitoring patients with AML for confirming or ruling out complete remission at the molecular level. The pattern of MPO mRNA positivity over time appears to be important and to correlate with clinical course, with sustained positivity being associated wtih impending relapse, while a switch from initial positivity to sustained negativity appears to be associated with long complete remssion. Studies of larger patient groups are necessary to confirm these initial findings.
Mol Diagn 1996 Dec
PMID:Use of Myeloperoxidase mRNA in Monitoring Patients With Acute Myelogenous Leukemia for Early Detection of Circulating Blasts. 1046 78


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