Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The report by Schacter et al. (J Biol Chem 247: 3601, 1972) that an antibody to NADPH-cytochrome c oxidoreductase inhibited NADPH-cytochrome c reductase and heme oxygenase activities in rat and pig liver and spleen microsomes demonstrated the role of this flavoprotein in microsomal heme oxygenation. Recent studies from other laboratories (Yoshida et al., J Biochem 75, 1187: 1974 and Bissell et al., Fed Proc 33: 1246, 1974) have strongly suggested that cytochrome P-450 is not involved in heme oxygenation. The availability of a homogeneous preparation of NADPH-cytochrome c reductase prompted us to test heme oxygenase activity in a system devoid of hemoprotein contamination. NADPH-cytochrome c reductase catalyzed biliverdin formation at a rate of 8.26 +/- 0.5 SEM nmole min-1mg-1 in the absence of biliverdin reductase. The rate of bilirubin formation in the presence of biliverdin reductase was less than 10% of the rate of biliverdin formation, suggesting that mixture of biliverdin isomers may be produced. Biliverdin production was potently (70--80%) inhibited by catalase, but was unaffected by superoxide dismutase. Epinephrine also inhibited heme oxygenation, presumably by utilizing O2. required for the formation of H2O2 by the reductase. By extrapolation, the NADPH oxidase activity due to NADPH-cytochrome c reductase can account for heme degradation occurring in microsomes. However, the specificity of ring scission at the IXalpha position must be due to another microsomal protein, perhaps the heme oxygenase of Yoshida et al., and not cytochrome P-450.
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PMID:The catalysis of heme degradation by purified NADPH-cytochrome C reductase in the absence of other microsomal proteins. 82 31

We previously showed that the supernatant of a Pseudomonas aeruginosa (PA) culture and its constituents pyocyanin and 1-hydroxyphenazine inhibit ciliary activity of dispersed tracheal epithelial cells in vitro via the generation of oxygen radicals by phagocytes. In the present study, we wished to determine if tracheal mucus velocity (TMV) is also impaired by PA supernatant and if oxygen radicals have a mediating role. In conscious sheep, TMV (measured with a radiographic method) was determined before and serially following aerosol challenge with the cell-free supernatant of a PA culture or unconditioned culture medium (control). TMV decreased from a mean (+/- SEM) baseline of 6.7 +/- 1.1 mm/min (n = 6) by 29, 35, and 25% at 0.5, 3, and 24 h after challenge, respectively (p < 0.05), and returned to baseline 1 wk later (-6%, p = NS). Control medium had no effect on TMV (maximum decrease by 15% at 0.5 h). Aerosolized catalase blunted the effect of PA supernatant on TMV. To determine if the impairment of TMV involved ciliary inhibition, tissues were mounted in a chamber and ciliary beat frequency (CBF) and surface liquid velocity (SLV) were measured with a microscopic method. PA supernatant decreased both CBF (maximum mean decrease 12%; n = 5, p < 0.05) and SLV (maximum mean decrease 78%; n = 5, p < 0.05) in a dose-dependent fashion, with a correlation between the two parameters; these effects were blocked by catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impairment of airway mucociliary transport by Pseudomonas aeruginosa products. Role of oxygen radicals. 144 66

Oxygen free radicals have been shown to play a major role in the development of perfusion abnormalities, contractile dysfunction, and irreversible injury in ischemic-reperfused myocardium. The aim of this study was to assess the direct protective effects of radical scavengers, calcium antagonists, and combination of these substances against free radical induced myocyte damage. Viability (% of rod-shaped cells) and adenine nucleotide content (AdN, high-pressure liquid chromatography) of isolated adult rat cardiomyocytes were measured after exposure to hypoxanthine (2 mM) and xanthine oxidase (25 mU/ml). After 90 min, viability of myocytes decreased to 4.2 +/- 3.4% (mean +/- SEM) of pre-exposure control, and AdN decreased from 28.2 +/- 1.8 to 8.09 +/- 1.1 nmol/mg protein. Addition of catalase (1500 U/ml) resulted in the preservation of viability (77 +/- 6% of pre-exposure control, n = 6, mean +/- SEM), and AdN 84 +/- 6%, p less than 0.001. These values are not significantly different from those measured in myocytes not exposed to free radicals (88 +/- 9% and 79 +/- 6%, respectively). Superoxide dismutase (2400 U/ml), dimethylthiourea (10 mM), and desferrioxamine (1 mM) did not preserve either viability or AdN. The calcium antagonist verapamil (10 microM) also preserved myocyte viability significantly (23 +/- 9.7%, p less than 0.05 vs unprotected cells), but failed to prevent the loss of AdN (13.2 +/- 4%, not significant as compared to unprotected cells). Viability and AdN in myocytes treated with nifedipine (10 microM) or diltiazem (10 microM) were not higher than in unprotected cells. All combined treatment forms which included catalase resulted in the preservation of myocyte viability as well as AdN. These data show that only the hydrogen peroxide scavenger catalase protects isolated cardiomyocytes against free radicals generated in the purine catabolic pathway.
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PMID:Oxygen free radical damage of isolated cardiomyocytes: comparative protective effect of radical scavengers and calcium antagonists. 159 Jul 37

We investigated the role of singlet oxygen (generated from photoactivation of rose bengal) on the calcium transport and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum (SR). Isolated cardiac SR exposed to rose bengal (10 nM) irradiated at 560 nm resulted in significant inhibition of Ca2+ uptake (from 2.27 +/- 0.05 to 0.62 +/- 0.05 mumol Ca2+/mg.min [mean +/- SEM], p less than 0.01) and Ca(2+)-ATPase activity (from 2.08 +/- 0.05 to 0.28 +/- 0.04 mumol Pi/min.mg [mean +/- SEM], p less than 0.01). The inhibition of calcium uptake and Ca(2+)-ATPase activity by rose bengal-derived activated oxygen (singlet oxygen) was dependent on the duration of exposure and intensity of light. Singlet oxygen scavengers ascorbic acid and histidine significantly protected SR Ca(2+)-ATPase against rose bengal-derived activated oxygen species, but superoxide dismutase and catalase did not attenuate the inhibition. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of SR exposed to photoactivated rose bengal for up to 14 minutes demonstrated complete loss of the Ca(2+)-ATPase monomer band, which was significantly protected by histidine. The addition of dithiothreitol (5 mM) had a slight protective effect, showing that new disulfide bond formation was not a major cause of aggregation. The results were also confirmed by high-performance liquid chromatography of the SR exposed to irradiated rose bengal. Irradiation of rose bengal also caused an 18% loss of total sulfhydryl groups of SR. On the other hand, superoxide radical (generated from xanthine oxidase action on xanthine) and hydroxyl radical (in the presence of Fe(3+)-EDTA or 0.5 mM H2O2 plus Fe(2+)-EDTA) as well as H2O2 (0.25-12 mM) were without any effect on the 97,000-d Ca(2+)-ATPase band of SR. Generation of radical species (superoxide and hydroxyl radical) from rose bengal was studied by electron paramagnetic resonance spectroscopy using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The results showed that irradiation of rose bengal formed a 1:2:2:1 quartet, characteristic of the DMPO-OH adduct, which was scavenged by ethanol but not by superoxide dismutase, catalase, or histidine. No radical species could be detected from irradiated rose bengal or irradiated DMPO under the assay conditions used. Peroxy adducts of DMPO might be produced but would be observed only at very low temperatures. Similarly, we could not detect any measurable.O2- anion from irradiation of rose bengal as indicated by either cytochrome c reduction at 550 nm or nitro blue tetrazolium reduction at 560 nm. These results show that SR is damaged most likely by singlet oxygen derived from rose bengal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Singlet oxygen interaction with Ca(2+)-ATPase of cardiac sarcoplasmic reticulum. 165 35

Earlier studies have demonstrated an improvement in the recovery of the regional myocardial function after reversible myocardial ischemia when dogs were treated with superoxide dismutase (SOD) + catalase (CAT). In all these studies, drug administration was started prior to the ischemic period. The aim of this study was to investigate the effects of SOD and CAT on the recovery of the regional contractile function in anesthetized beagle dogs when the drugs were administered at the time of reperfusion. The animals were subjected to 20 min of left coronary artery occlusion followed by 3 h reperfusion. The regional myocardial contractile function, measured as subendocardial segment shortening (SS, sonomicrometry) decreased to below zero and the regional blood flow in the ischemic subendocardium was reduced to about 5% of pre-ischemic values during the coronary artery occlusion period. The size of the occluded bed was similar in the two groups. Saline (n = 8) or SOD (10 mg/kg) + CAT (3.4 mg/kg) (n = 8) were infused into the left atrium from 2.5 min prior to until 20 min after the start of reperfusion. The peak plasma level of SOD was 102 +/- 15 mg/l at 20 min reperfusion. There were no significant differences in the arterial blood pressure, cardiac contractile function and regional blood flow between the two groups at any time during the experiment. During reperfusion in the dogs given vehicle, SS recovered to 48 +/- 7% (mean +/- SEM) after the first hour of reperfusion, and to 51 +/- 6% of pre-ischemic values after 3 h of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Superoxide dismutase and catalase do not improve recovery of regional myocardial contractile function when given at the time of reperfusion after reversible regional ischemia in anesthetized dogs. 177 87

The internal mammary artery (IMA) has become the conduit of choice in coronary artery bypass surgery because of superior long-term patency. It had been shown that IMA graft could release prostacyclin. Prostacyclin is a potent vasodilator and also can inhibit platelet aggregation. To determine the role of human IMA endothelium in production of prostacyclin, we tested the reactivity of segments of human IMA to hypoxia in vitro. Human IMAs were harvested during coronary artery bypass surgery. Prostacyclin was measured from fluid in the organ baths by radioimmunoassay of its major hydrolytic product 6-keto-prostaglandin F1 alpha. Rings (4 mm in length) of IMA, with and without endothelium, were suspended in organ baths containing physiologic salt solution. Rings were contracted with norepinephrine, and exposed to hypoxia (pO2 35 +/- 5 mmHg) for 15 minutes then reoxygenated. In segments with endothelium, hypoxia induced a transient relaxation followed by contraction. The transient relaxation was associated with a significantly increased production of 6-keto-prostaglandin-F1 alpha (from 34.1 +/- 2.7 pg/ml prehypoxia to 51.6 +/- 6.7 pg/ml during hypoxia, mean +/- SEM, p less than 0.05). This transient relaxation was blocked by indomethacin but not by NG-monomethyl-L-arginine (L-NMMA) and free radical scavengers (superoxide dismutase, catalase and deferoxamine). However, in segments without endothelium, the prehypoxia (14.7 +/- 0.9) and during hypoxia (15.5 +/- 1.4) level of 6-keto-prostaglandin F1 alpha were not increased and were significantly lower than those with endothelium. This study demonstrated that endothelium of IMA grafts could release prostacyclin either in a basal condition or upon stimulation of hypoxia. This ability possibly contributes to its long-term patency.
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PMID:Endothelium-dependent production of prostacyclin in human internal mammary artery. 179 65

It has been reported that agents having the ability to scavenge oxygen-derived free radicals reduce the severity of ventricular arrhythmias that occur after brief coronary occlusion and reperfusion. Superoxide dismutase plus catalase (SOD + CAT) or placebo was administered in a blinded randomized fashion prior to coronary occlusion in rats (n = 25 each group) undergoing a 5-min left coronary occlusion followed by 15 min of reperfusion. During reperfusion, ventricular tachycardia (VT) developed in 96% of animals in both groups. Reperfusion ventricular fibrillation (VF) developed in 60% of the placebo group vs 56% in the SOD + CAT group (p = 1.0). Irreversible VF occurred in 40% of the placebo group vs 20% in the SOD + CAT group (p = 0.22). Atrioventricular block occurred in 12% of placebo and 4% of SOD + CAT animals (p = 0.61). There were no significant difference between groups in duration of VT (85 +/- 15 s (mean +/- SEM) placebo vs 81 +/- 14 s SOD + CAT, p = 0.81), total duration of VT plus VF (391 +/- 76 s placebo vs 256 +/- 64 SOD + CAT, p = 0.45) or numbers of single ventricular ectopic beats (65 +/- 15 placebo vs 97 +/- 18 SOD + CAT, p = 0.18). Heart rate at reperfusion was slightly higher in control than SOD + CAT animals (340 +/- 33 vs 319 +/- 32, p = 0.02). Risk zone size, determined by Monastral blue injection, was equal in both groups (34 +/- 2% of ventricular mass). The occurrence of reperfusion VF in this model could not be predicted by heart rate at reperfusion (331 +/- 33 VF animlas vs 328 +/- 36 no VF, p = 0.77), or by risk zone size (34 +/- 2%, VF and no VF groups).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of significant effects of superoxide dismutase and catalase on development of reperfusion arrhythmias. 187 67

Bradykinin produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. The goals of this study were to determine the mediator of bradykinin-induced dilatation in cerebral arterioles of rats and to determine whether responses to this mediator are altered in hypertensive rats. Diameter of pial arterioles (20-65 microns) was measured using intravital microscopy in 18 normotensive and 17 hypertensive rats. Superfusion of 3 x 10(-7) M bradykinin dilated pial arterioles by 53 +/- 4% (mean +/- SEM) in normotensive rats but only 33 +/- 6% in hypertensive rats (p less than 0.05 versus normotensive rats). Vasodilatation in response to bradykinin was almost completely inhibited by 280 units/ml catalase in both normotensive and hypertensive rats (n = 7 and n = 7, respectively) whereas 150 units/ml superoxide dismutase (n = 6 and n = 5, respectively) and 1 mM deferoxamine (n = 5 and n = 5, respectively) did not attenuate bradykinin-induced vasodilatation. These findings suggest that hydrogen peroxide is the mediator of bradykinin-induced dilatation in cerebral arterioles of rats. We also examined responses of cerebral arterioles to hydrogen peroxide in five normotensive and six hypertensive rats. Dilator responses of cerebral arterioles to 3.2 x 10(-5) M to 1.6 x 10(-4) M hydrogen peroxide did not differ in normotensive and hypertensive rats, which suggests that impaired dilatation of cerebral arterioles in response to bradykinin is not related to altered responsiveness of smooth muscle to an endothelium-derived relaxing factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of impaired endothelium-dependent cerebral vasodilatation in response to bradykinin in hypertensive rats. 192 61

By the production of microbicidal agents, such as reactive oxygen species, activated PMN are capable of inducing tissue damage in the host. TNF-alpha was recently shown to be a potent activator of PMN oxidative metabolism. To further evaluate the interaction between activated PMN with physiological target cells, the effect of human PMN on cultured bovine aortic and human umbilical vein endothelial cells (EC) upon stimulation with human TNF-alpha was investigated by ultrastructural techniques: Scanning and transmission electron microscopy (SEM and TEM resp.) and ultrastructural detection of H2O2 production. When isolated PMN were added to EC in the presence of recombinant human TNF-alpha (10(3) U/ml) the EC-monolayer was disrupted within 4 h and EC changed their shape by exhibiting a spindle-like structure. PMN were seen in the intercellular spaces. Release of H2O2 was observed at the surface of the PMN plasma membrane, the luminal part of the small intracytoplasmic vacuoles in the PMN as well as in the contact zone between PMN and EC, but not within the EC. Scavengers of reactive oxygen species, such as superoxide dismutase and catalase or D-mannitol failed to block the effect of TNF-alpha-stimulated PMN on EC. In contrast, addition of NaN3 (0.1 mM), an inhibitor of myeloperoxidase activity, almost completely inhibited the disruption of EC-monolayers. Subsequent addition of NaN3-insensitive horseradish peroxidase reconstituted the effect. The results obtained suggest that TNF-alpha-stimulated PMN effectively cause the disruption of EC monolayers by an adherence-dependent mechanism which is mediated by the release of myeloperoxidase. The results may be of major importance for the pathogenesis of inflammatory vascular reactions.
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PMID:Interaction of granulocytes and endothelial cells upon stimulation with tumor necrosis factor-alpha: an ultrastructural study. 209 2

To define the relation between oxygen-derived free radical (oxy-radical) generation in the reperfused ischemic myocardium and the progression of myocardial damage, we measured oxy-radical generation in the ischemic myocardium and the propagating infarct size in a model of canine coronary occlusion (90 minutes) and reperfusion. We used electron paramagnetic resonance spin-trapping techniques (5,5-dimethyl-1-pyrroline N-oxide [DMPO]) to detect oxy-radicals in the rapidly frozen myocardial samples taken by needle biopsy. There was no detectable generation of DMPO adducts in the normal myocardium before or after reperfusion. In the reperfused ischemic myocardium, electron paramagnetic resonance signals of DMPO-OOH (superoxide anion) and DMPO-OH (hydroxyl radical) were detected, with peak concentrations at 1 hour after reperfusion for DMPO-OOH and at 3 hours after reperfusion for DMPO-OH, respectively. These DMPO adducts were also detected during the early phase (15 seconds) of reperfusion, but the concentrations of these signals were much less than those during the late phase of reperfusion. Treatment with human recombinant superoxide dismutase (2.5 mg/kg/hr) and catalase (2.5 mg/kg/hr) during the course of experiments abolished DMPO-OOH formation but had little effect on DMPO-OH formation. Infarct size (percent of risk area infarcted), quantified by a dual staining method with Evans blue dye and triphenyltetrazolium chloride, was 18.3 +/- 4.8% (mean +/- SEM) at 90 minutes of occlusion. After 5 hours of reperfusion, infarct size increased to 43.6 +/- 7.2%. These results indicate that a greater magnitude of oxy-radical generation was sustained in the ischemic myocardial tissue during the late phase (1-3 hours) of reperfusion, associated with the progression of myocardial infarction. The concurrent appearance of oxy-radicals and progressive infarction may support the view that a chain reaction of oxy-radicals contributes to the propagation of myocardial cell damage in the postischemic heart.
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PMID:Detection of oxygen-derived free radical generation in the canine postischemic heart during late phase of reperfusion. 231 92


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