Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of leukocytes results in the release of a variety of vasoactive substances that may modulate vascular tone. We studied the effect of human polymorphonuclear (PMN) and mononuclear (MONO) leukocytes on quiescent femoral arteries in vitro. Arteries were obtained from normal and atherosclerotic cynomolgus monkeys. In normal arteries, stimulation of PMNs (3 and 5 x 10(6) cells/ml) with either thrombin (5 units/ml) or complement C5a (0.5 micrograms/ml) resulted in endothelium-independent contraction (approximately 25% of maximum contraction with 80 mM KCl). Vasocontraction was augmented in the presence of superoxide dismutase (150 units/ml) and was significantly impaired in the presence of the hydroxyl radical scavengers mannitol (20 mM) and deferoxamine (1 mM). Catalase (1,200 units/ml) or L-alanine (20 mM) did not modify this effect of PMNs. In contrast to PMNs, vasocontraction in response to MONOs was not altered by the addition of radical scavengers. Pretreatment of PMNs and MONOs with indomethacin (10 microM) or nordihydroguaiaretic acid (20 microM) did not influence vascular responses. Supernatant of thrombin-stimulated PMNs and MONOs also produced vasocontraction (approximately two thirds of the effect of intact cells). This vasocontractor factor (or factors) was heat stable (30 minutes, 95 degrees C) and had a molecular weight less than 1,000 as determined by ultrafiltration. Stimulation of MONOs or PMNs (3 and 5 x 10(6) cells/ml) produced a similar response in normal arteries. In contrast, the constrictor response in atherosclerotic arteries to MONOs (5 x 10(6) cells/ml) was significantly greater than to PMNs. We conclude that stimulated human PMNs and MONOs contract arteries in vitro by release of at least two factors. One factor appears to be heat stable, with a molecular weight less than 1,000. The vascular response to PMNs, but not to MONOs, appears to involve the generation of hydroxyl radicals. The response to MONOs is greater than the response to PMNs in atherosclerotic, but not in normal, arteries.
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PMID:Mechanisms of contraction induced by human leukocytes in normal and atherosclerotic arteries. 187 79

Human blood platelets produce oxidant species when stimulated by collagen and thrombin. The oxidative burst of platelets has been studied by cytofluorimetry taking advantage of the fluorogenic dye DCFH2-DA, which is taken up and deacetylated by platelets and then oxidized to the fluorescent derivative DCF. The oxidation of DCFH2 is induced by stimulation with collagen but not with thrombin and inhibited by external catalase. Catalase also inhibited the aggregation induced by collagen, but not that induced by thrombin. Aspirin and indomethacin inhibited the formation of the fluorochrome only when platelets were stimulated by thrombin. Externally added H2O2 increased the cytoplasmic calcium content as probed by the fluorescence of Indo-1. The present data suggest that collagen induces the production of H2O2, which in turn may stimulate the aggregation of platelets through a calcium mobilization. Instead the stimulation by thrombin does not require the intermediacy of H2O2.
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PMID:Hydrogen peroxide is an intermediate in the platelet activation cascade triggered by collagen, but not by thrombin. 189 57

1. Superoxide dismutase (SOD, 60 u ml-1) or ferricytochrome c (70 microM) significantly inhibited thrombin-stimulated platelet adhesion to gelatin-coated plastic, whereas catalase (1000 u ml-1) or mannitol (1 mM) had no effect. 2. The platelet aggregation induced by low concentrations of thrombin (causing less than 45% maximal change in light transmission) was inhibited by SOD. Catalase or mannitol had no effect on platelet aggregation. 3. Pyrogallol (an O2- generator) enhanced both platelet adhesion to gelatin-coated plastic and platelet aggregation induced by thrombin; this enhancement was neutralized by SOD. 4. These results indicate that O2- increase both platelet adhesion and aggregation, whereas other free radicals such as hydrogen peroxide or hydroxyl radicals are not involved.
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PMID:Superoxide anions enhance platelet adhesion and aggregation. 255 40

Hydrogen peroxide (H2O2) increases adherence of human polymorphonuclear neutrophils (PMN) to cultured human umbilical vein endothelial cells (HUVEC). Catalase and HO. scavengers did not affect the increased PMN adherence to HUVEC stimulated by other compounds such as phorbol myristate acetate (PMA) and thrombin, showing that the observed effect was H2O2- and HO.-specific. This effect was inhibited by hydroxyl radicals (HO.) scavengers and not by iron-chelators that do not penetrate the cells, suggesting the involvement of intracellular HO. in the increased adherence mechanism. An increase in cAMP inhibited H2O2-induced adherence, as observed with isoproterenol, isobutylmethylxanthine, and dibutyryl-cAMP. Similarly, pentoxifylline (Ptx), an HO. scavenger that also increases cAMP, inhibited H2O2-mediated adherence but had no effect on that induced by PMA or thrombin. PKA inhibitors cancelled the Ptx-induced inhibition of H2O2-mediated adherence. However, PKA inhibitors or atrial natriuretic peptide that decreases cAMP did not increase adherence, showing that decrease in cAMP is not responsible for increased adherence. HO. scavengers did not alter the H2O2-induced reduction in cAMP levels, but did inhibit the effect of H2O2 on adherence. We conclude that HO. mediates the H2O2-induced increased in PMN adherence to HUVEC, and that the increase in cAMP that mediates PKA activation downregulates this effect.
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PMID:Inhibition of human neutrophil binding to hydrogen peroxide-treated endothelial cells by cAMP and hydroxyl radical scavengers. 879 Oct 89

In this study, we investigated whether (1) collagen-induced platelet aggregation is associated with a burst of H2O2, (2) this oxidant species is involved in the activation of platelets, and (3) the pathways of platelet activation are stimulated by H2O2. Collagen-induced platelet aggregation was associated with production of H2O2, which was abolished by catalase, an enzyme that destroys H2O2. H2O2 production was not observed when ADP or thrombin were used as agonists. Catalase inhibited dose-dependently thromboxane A2 production, release of arachidonic acid from platelet membrane, and Inositol 1,4,5P3 (IP3) formation. In aspirin-treated platelets stimulated with high concentrations of collagen, catalase inhibited platelet aggregation, calcium mobilization, and IP3 production. This study suggests that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.
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PMID:Hydrogen peroxide is involved in collagen-induced platelet activation. 942 1

There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.
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PMID:Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase. 1197 87

Cytosolic Ca2+ mobilization, especially Ca2+ entry, is enhanced in platelets from type 2 diabetic individuals, which might result in platelet hyperaggregability. In the present study, we report an increased oxidant production in resting and stimulated platelets from diabetic donors. Pretreatment of platelets with catalase or trolox, an analog of vitamin E, reversed the enhanced Ca2+ entry, evoked by thapsigargin plus ionomycin or thrombin, observed in platelets from diabetic subjects, so that in the presence of these scavengers Ca2+ entry was similar in platelets from healthy and diabetic subjects. In contrast, mannitol was without effect on Ca2+ mobilization. Catalase and trolox reduced thrombin-induced aggregation in platelets from type 2 diabetic subjects, while mannitol did not modify thrombin-induced platelet hyperaggregability. We conclude that H2O2 and ONOO- are likely involved in the enhanced Ca2+ mobilization observed in platelets from type 2 diabetic patients, which might lead to platelet hyperactivity and hyperaggregability.
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PMID:Hydrogen peroxide and peroxynitrite enhance Ca2+ mobilization and aggregation in platelets from type 2 diabetic patients. 1596 63