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)

Polymorphonuclear leukocytes have been shown to play an important role in myocardial ischemia (MI) and reperfusion (R) injury. Since blockade of platelet-endothelial cell adhesion molecules (PECAM-1) inhibits neutrophil transmigration in vitro and in vivo, the effects of a polygonal Ab directed against PECAM-1 were examined in a feline model of Ml/R. We established cross-reactivity of our anti-human PECAM-1 Ab to cat coronary vasculature and neutrophils by immunohistochemistry and flow cytometry. The anti-PECAM-1 Ab markedly blocked leukocyte transmigration into the peritoneal cavity of cats after glycogen-induced peritonitis. Then, anti-PECAM-1 Ab (1 mg/kg) was tested to determine whether it attenuates MI/R injury in a well characterized feline model of Ml and R. Anti-PECAM-1 Ab administered 10 min before R significantly inhibited the myocardial necrosis seen 4.5 h post-R compared with that in MI/R cats treated with control isotype rabbit IgG (12 +/- 2 vs 29 +/- 4% of area at risk; p less than 0.01) and significantly attenuated the rise in plasma creatine kinase activity (p less than 0.05). The Ab did not prevent increases in cardiac myeloperoxidase activity within the affected regions and did not significantly inhibit autologous neutrophil adhesion to coronary endothelium after stimulation of either neutrophils (by leukotriene B4) or coronary endothelium (by thrombin) in vitro. These results indicate that in vivo blockade of PECAM-1 significantly attenuates MI/R injury, presumably by inhibiting transendothelial migration of neutrophils.
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PMID:Blockade of platelet endothelial cell adhesion molecule-1 protects against myocardial ischemia and reperfusion injury in cats. 861 85

The present review has summarized the expression, production and effects of the human interleukins (IL) 1-11 and myelopoietic colony stimulating factors (CSF) in the established myeloid leukemia cell lines and in cells from patients with acute myeloid leukemia as well as the oncogene expression reported in these myeloid leukemia cell lines. The genetic dissection of leukemic myelopoiesis may provide new perspectives for the control of myeloid leukemias. Based on their expression of phenotypic markers (e.g., surface antigens, cytochemical staining, etc.), myeloid cell lines can be further subdivided into myelogenous, monocytic, erythroid and megakaryoblastic leukemia cell lines. Due to the close relationship of erythroid and megakaryoblastic progenitor cells and to the existence of a probably common precursor cell giving rise to these two different cell lineages, many megakaryoblastic cell lines express erythroid markers (e.g., expression of hemoglobin or glycophorin A) and conversely cell lines with a predominant erythroid profile might display megakaryoblastic features (e.g., platelets peroxidase or glycoproteins CD41, CD42b or CD61). The recent cloning of the specific cytokine: thrombopoietin (TPO) and its receptor generated a strong interest in these particular myeloid cell lines that are discussed in more detail in the present review. Both normal and leukemic megakaryocytopoiesis are stimulated by granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3, GM-CSF/IL-3 fusion protein, IL-6, IL-11 and TPO but inhibited by IL-4, interferon-alpha (IFN-alpha) and IFN-gamma. Human megakaryoblastic leukemia cell lines have common biological features: high expression of the megakaryocytic specific antigen (CD41); high expression of early myeloid antigens (CD34, CD33 and CD13); constitutive expression of IL-6 and platelet-derived growth factor; a complex karyotype picture; expression of c-kit (the stem cell factor receptor); growth-dependency or -stimulation by IL-3 and/or GM-CSF; and in vivo tumorigenicity in mice associated with marked fibrosis. Whereas numerous chemical and biologic agents induce granulocytic and/or monocytic differentiation of myeloid leukemia cell lines, only a few agents including phorbol myristate acetate, vitamin D3, IFN-alpha, IL-6 and thrombin have been reported to induce megakaryocytic differentiation in the megakaryoblastic leukemia cells.
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PMID:Interleukins and colony stimulating factors in human myeloid leukemia cell lines. 875 Jun 18

The effect of a selective leukotriene receptor antagonist, the peptide ICI 198,615, on thrombin-induced pulmonary edema was studied in rats. Administration of thrombin produced a significant increase in lung weight (p < 0.05), wet weight to dry weight ratio (WW/DW; p < 0.05), and relative lung water content (p < 0.05). These increases were all significantly reduced (p < 0.05) by ICI 198,615 (bolus 15 mg/kg, infusion 15 mg/kg/h). Thrombin infusion caused a significant increase in myeloperoxidase activity in the lung tissue (p < 0.05). This increase was further accentuated by ICI 198,615, indicating that the effect of this antagonist is not due to reduction of leukocyte infiltration in the lungs. The results thus show that a leukotriene receptor antagonist effectively counteracts the increase in lung vascular permeability to protein caused by thrombin, and indicate that leukotrienes are important mediators of thrombin-induced pulmonary edema in the rat.
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PMID:Beneficial effects of a leukotriene receptor antagonist on thrombin-induced pulmonary edema in the rat. 882 Nov 25

1. The efficacy of oligotide, a single stranded polydeoxyribonucleotide complex, was examined in a feline model of myocardial ischaemia (MI: 90 min) and reperfusion (R: 270 min). Oligotide (15 mg kg-1 bolus) was administered intravenously 80 min after occlusion of the left anterior descending (LAD) coronary artery (i.e., 10 min prior to R) and continued for an additional 280 min (10 mg kg-1 h-1 infusion). 2. Oligotide-treated cats showed significantly smaller myocardial necroses and lower cardiac myeloperoxidase activities (significantly lower neutrophil infiltration) in the necrotic zone as compared to MI+R cats receiving only vehicle. 3. LAD coronary arteries isolated from MI+R cats exhibited a significant endothelial dysfunction (i.e., reduced endothelium-dependent relaxation), and significantly increased adherence of polymorphonuclear neutrophils (PMNs) ex vivo. However, oligotide significantly preserved endothelial function and attenuated PMN adherence in ischaemic LAD coronary arteries. 4. Oligotide attenuated P-selectin expression on thrombin-stimulated platelets as well as PMN adherence to thrombin-stimulated coronary endothelium. Immunohistochemical examination in vivo revealed that oligotide treatment also significantly inhibited coronary endothelial P-selectin expression after 90 min MI and 20 min R. 5. Oligotide exerted a significant cardioprotection in MI+R injury. The mechanism appears to be related to attenuation of PMN-endothelial interaction and eventual infiltration into the ischaemic myocardium.
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PMID:Cardioprotective actions of oligotide, a single stranded polydeoxyribonucleotide complex, in myocardial ischaemia and reperfusion injury. 888 89

In the present study, we differentiated between short- and long-term effects of vasoactive compounds on human endothelial permeability in an in vitro model. Histamine induced a rapid and transient (<3 minutes) decrease in barrier function, as evidenced by a decreased transendothelial electrical resistance and an increased passage of 22Na ions. This increase in permeability was inhibited completely by chelation of intracellular calcium ions by BAPTA-AM and inhibition of calmodulin activity and myosin light chain (MLC) phosphorylation. The presence of serum factors prolonged the barrier dysfunction induced by histamine. Thrombin by itself induced a prolonged barrier dysfunction (>30 minutes) as evidenced by an increased passage of peroxidase and 40 kDa dextran. It was dependent only partially on calcium ions and calmodulin. The protein tyrosine kinase inhibitors genistein and herbimycin A, but not the inactive analogue daidzein, inhibited to a large extent the increase in permeability induced by thrombin. Genistein and BAPTA-AM inhibited the thrombin-induced permeability in an additive way, causing together an almost complete prevention of the thrombin-induced increase in permeability. Inhibition of protein tyrosine kinase was accompanied by a decrease in MLC phosphorylation and a reduction in the extent of F-actin fiber and focal attachment formation. Inhibition of RhoA by C3 transferase toxin reduced both the thrombin-induced barrier dysfunction and MLC phosphorylation. Genistein and C3 transferase toxin did not elevate the cellular cAMP levels. No evidence was found for a significant role of protein kinase C in the thrombin-induced increase in permeability or in the accompanying MLC phosphorylation. These data indicate that in endothelial cell monolayers that respond to histamine in a physiological way, thrombin induces a prolonged increase in permeability by "calcium sensitization," which involves protein tyrosine phosphorylation and RhoA activation.
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PMID:Transient and prolonged increase in endothelial permeability induced by histamine and thrombin: role of protein kinases, calcium, and RhoA. 983 6

We investigated whether antithrombin (AT) can reduce ischemia/reperfusion (I/R)-induced injury of rat liver by promoting prostacyclin release from endothelial cells. Although intravenous administration of AT (250 U/kg) markedly reduced hepatic injury, neither dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, nor Trp49-modified AT, which lacks affinity for heparin, had any effect. Hepatic levels of 6-keto-PGF1, a stable prostacyclin (PGI2) metabolite, were increased significantly after I/R of the rat liver. AT significantly increased the hepatic level of 6-keto-PGF1, whereas neither DEGR-Xa nor Trp49-modified AT increased it. Hepatic tissue blood flow was markedly reduced after I/R. Although AT significantly increased the hepatic tissue blood flow after I/R, neither DEGR-Xa nor Trp49-modified AT increased the blood flow. Hepatic levels of cytokine-induced neutrophil chemoattractant (CINC) and myeloperoxidase (MPO) were significantly increased after hepatic I/R. The levels of these two indicators were reduced by AT but were unaffected by either DEGR-Xa or Trp49-modified AT. Pretreatment of animals with indomethacin (IM) completely inhibited the protective effects of AT on the I/R-induced hepatic damage and the leukocyte activation as well as the AT-induced increase in hepatic 6-keto-PGF1 levels after I/R. Iloprost, a stable analog of PGI2, exhibited effects similar to those of AT and also significantly inhibited the exacerbation of liver injury, the decrease in hepatic tissue blood flow, and the increases in hepatic CINC and MPO levels seen in rats subjected to I/R but pretreated with IM. These findings suggest that AT may prevent I/R-induced hepatic injury by increasing the hepatic levels of PGI2 through the interaction of AT with cell-surface glycosaminoglycans, thus increasing hepatic tissue blood flow and inhibiting leukocyte activation in animals subjected to I/R.
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PMID:Antithrombin reduces ischemia/reperfusion injury of rat liver by increasing the hepatic level of prostacyclin. 986 57

The effect of a selective leukocyte elastase inhibitor, ICI 200,355, on thrombin-induced pulmonary oedema was studied in rats. Thrombin administration produced an increase in lung weight (P < 0.05), wet weight/ dry weight ratio (P < 0.05), and relative lung water content (P < 0.05). The lung weight increase was reduced by the elastase inhibitor in doses of 2000, 200 and 20 micrograms/kg per h (P < 0.05), but not by 2 micrograms/kg per h. A dose of 20 micrograms/ kg per h seems to be optimal, since 10-fold and 100-fold increases in dose did not further improve the effect. Free elastase activity in lung tissue was higher after thrombin infusion than in controls, but was not depleted by the elastase inhibitor in vivo (P < 0.05). This elastase activity in the lung was, however, inhibited by the elastase inhibitor in vitro, indicating that the inhibitor can block extracellular, but not intracellular elastase activity. Thrombin infusion resulted in a significant decrease in plasma elastase inhibitory capacity (P < 0.05), which was depleted by the elastase inhibitor (20 micrograms/kg per h) (P < 0.05). Myeloperoxidase activity was significantly increased in lung tissue after thrombin infusion (P < 0.05). Lung myeloperoxidase activity 5 min after thrombin infusion was not affected by the elastase inhibitor, but the inhibitor induced a further increase in myeloperoxidase as seen 90 min after thrombin infusion, indicating that the effect of this inhibitor on pulmonary oedema is not due to reduction of leukocyte infiltration in the lungs, but may partly be exerted by prevention of neutrophil destruction.
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PMID:A leukocyte elastase inhibitor reduces thrombin-induced pulmonary oedema in the rat: mechanisms of action. 1010 47

Biodegradation of poly(urethane)s (PU)s using single enzymes in vitro was assessed by measuring radiolabel release from model poly(ester-urea-urethane) (PESU) and poly(ether-urea-urethane) (PETU) materials synthesized with 14C-labelled monomers. Cholesterol esterase (CE), an enzyme found in monocyte-derived macrophages (MDM), has been reported to cause a significant level of radiolabel release from both of these PUs. Previous work has shown that CE activity could be inhibited by the serine protease/esterase inhibitor, phenylmethylsulfonyl fluoride. Since many serine proteases are present in circulating blood and can be released by cells other than MDM, this study investigated the ability of serine proteases relative to that of CE to cause the degradation of PUs. In addition, the possible role of several oxidative enzymes in the breakdown of PUs was investigated. Proteinase K, chymotrypsin and thrombin, when incubated with PESU, coated on glass slips, caused significant radiolabel release, with proteinase K giving the highest values. However, the highest radiolabel release which proteinase K could elicit was ten times less than CE. Thrombin and then chymotrypsin were progressively worse in their biodegradative activity. Only CE, and not the serine proteases, could elicit a detectable radiolabel release from PETU. Although the release of reactive oxygen species and molecular oxygen occur around an implanted biomaterial, several oxidative systems (peroxidase, xanthine oxidase, catalase), known to produce one or more of these molecular species, were unable to induce radiolabel release from these PUs. The process of biodegradation as assessed by radiolabel release appears to be a specific hydrolytic process, while the role of oxidative enzymes remains less clear.
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PMID:The biodegradation of poly(urethane)s by the esterolytic activity of serine proteases and oxidative enzyme systems. 1042 27

The effects of recombinant soluble P-selectin glycoprotein ligand-1 (rsPSGL.Ig) were studied after 120 min of splanchnic artery occlusion and 120 min of reperfusion (SAO/R). SAO/R rats administered a low-affinity mutant form of rsPSGL.Ig exhibited signs of severe circulatory collapse with marked hypotension, a survival time of only 37+/-16 min, and significant increases in intestinal myeloperoxidase (MPO) activity (P<0.01). In addition, SAO/R rats given rsPSGL.Ig low-affinity mutant showed severe endothelial dysfunction characterized by a blunted vasorelaxation to the endothelium-dependent vasodilator acetylcholine in comparison to sham-operated controls (30+/-9% vs. 97+/-3%). Administration of rsPSGL.Ig (0.5 mg/kg) significantly improved mean arterial blood pressure and increased survival time to 107+/-13 min (P <0.01). rsPSGL.Ig treatment also resulted in a significant attenuation in both intestinal MPO activity as well as the SAO/R-induced decline in endothelium-dependent vasorelaxation of superior mesenteric artery rings (P<0.01). In addition, rsPSGL.Ig attenuated in vitro neutrophil adherence to thrombin-stimulated superior mesenteric artery endothelium to a comparable degree as a P-selectin monoclonal antibody. These data suggest that rsPSGL.Ig provides beneficial effects by preserving endothelial function and attenuating neutrophil-endothelial cell interactions in the splanchnic circulation following ischemia-reperfusion.
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PMID:Acute mesenteric ischemia and reperfusion: protective effects of recombinant soluble P-selectin glycoprotein ligand-1. 1048 98

Accumulation of oxidized proteins has been demonstrated in the brain of patients suffering from Alzheimer's disease (AD). Among the proteins found in cerebral amyloid deposits, apolipoprotein (apo) E is a polymorphic protein which one specific isoform, apo E4, has been widely associated with AD. Apo E may be linked with AD by its isoform-specific interaction with lipids or other proteins in amyloid plaques. Using the myeloperoxidase oxidative system, we report that oxidation of the three recombinant apo E isoforms is differential (as estimated using immunoblot and high-performance liquid chromatography analysis), with apo E4 being more susceptible than apo E3, which in turn is much more susceptible than apo E2. In addition, susceptibility to thrombin proteolysis is reduced when apo E is oxidized, and oxidation of apo E decreases its incorporation into phospholipid discs by approximately 50%. Oxidation of apo E may contribute to inefficient lipid recycling in the brain, particularly regarding apo E4 and E3. Our results link and strengthen both the E4 allele linkage with AD and the role of protein oxidation in AD. The cerebral mechanisms underlying apo E oxidation and/or myeloperoxidase functions in vivo remain to be assessed.
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PMID:Differential oxidation of apolipoprotein E isoforms and interaction with phospholipids. 1065 99


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