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)

We have used 125I-labeled fibronectin (FN) as an extracellular substrate for neutrophils (PMN) in order to investigate the mechanism responsible for FN solubilization by PMN and the effects of recombinant cytokines on this process. Pure active alpha 1-antitrypsin (alpha 1AT), when added to PMN before or during, but not after, adherence to FN, inhibited solubilization of the substrate in a dose-dependent manner, but alpha 1AT that had been inactivated by proteolysis or oxidation and alpha 1AT Pittsburgh (alpha 1AT 358Met-Arg) had no significant effect. The solubilization of FN was also inhibited by the PMN elastase inhibitor N-methoxysuccinyl-alanyl-alanyl-prolyl-valine-chloromethylketone but not by the chymotrypsin and cathepsin G inhibitor N-Cbz-glycyl-glycyl-phenylalanine-chloromethylketone, nor by catalase or superoxide dismutase. The products of solubilization of FN by PMN, analyzed by sodium dodecyl sulphate polyacrylamide electrophoresis, were similar to those produced by pure PMN elastase but not cathepsin G. These results suggest that FN solubilization by PMN is caused largely by the pericellular activity of PMN elastase. The solubilization of FN by PMN was increased significantly by adding tumor necrosis factor-alpha, interleukin-1 alpha, or interferon-gamma to the adherent cells but without a significant general release of elastase into the culture supernatants. Granulocyte/macrophage colony-stimulating factor (GM-CSF) had no significant effect. None of the cytokines had any effect when preincubated with the cells in suspension, and non increased FN solubilization by PMN incubated with the optimal (10(-6) mol/liter) or suboptimal dose (10(-8) mol/liter) of the peptide formylmethionylleucylphenylalanine.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Apr
PMID:Extracellular proteolysis of fibronectin by neutrophils: characterization and the effects of recombinant cytokines. 201 99

Human liver manganese superoxide dismutase has been purified by a short procedure that includes a tri-phase partitioning step to provide materials that can be crystallized from ammonium sulfate. X-ray diffraction studies at 3 A resolution show that the crystals belong to the hexagonal space group P6(1)22 or P6(5)22, with cell dimensions a = b = 81.1 A, c = 242.2 A. Manganese superoxide dismutase levels as determined by enzymatic assay as well as by enzyme-linked immunosorbent assay indicated that considerable variations occur in different livers but the total superoxide dismutase activity (Mn superoxide dismutase plus Cu,Zn superoxide dismutase) seems to be kept at constant values.
J Mol Biol 1991 May 05
PMID:Preparation of human manganese superoxide dismutase by tri-phase partitioning and preliminary crystallographic data. 202 55

The structure of Mn(III) superoxide dismutase (Mn(III)SOD) from Thermus thermophilus, a tetramer of chains 203 residues in length, has been refined by restrained least-squares methods. The R-factor [formula: see text] for the 54,056 unique reflections measured between 10.0 and 1.8 A (96% of all possible reflections) is 0.176 for a model comprising the protein dimer and 180 bound solvents, the asymmetric unit of the P4(1)2(1)2 cell. The monomer chain forms two domains as determined by distance plots: the N-terminal domain is dominated by two long antiparallel helices (residues 21 to 45 and 69 to 89) and the C-terminal domain (residues 100 to 203) is an alpha + beta structure including a three-stranded sheet. Features that may be important for the folding and function of this MnSOD include: (1) a cis-proline in a turn preceding the first long helix; (2) a residue inserted at position 30 that distorts the helix near the first Mn ligand; and (3) the locations of glycine and proline residues in the domain connector (residues 92 to 99) and in the vicinity of the short cross connection (residues 150 to 159) that links two strands of the beta-sheet. Domain-domain contacts include salt bridges between arginine residues and acidic side chains, an extensive hydrophobic interface, and at least ten hydrogen-bonded interactions. The tetramer possesses 222 symmetry but is held together by only two types of interfaces. The dimer interface at the non-crystallographic dyad is extensive (1000 A2 buried surface/monomer) and incorporates 17 trapped or structural solvents. The dimer interface at the crystallographic dyad buries fewer residues (750 A2/monomer) and resembles a snap fastener in which a type I turn thrusts into a hydrophobic basket formed by a ring of helices in the opposing chain. Each of the metal sites is fully occupied, with the Mn(III) five-co-ordinate in trigonal bipyramidal geometry. One of the axial ligands is solvent; the four protein ligands are His28, His83, Asp166 and His170. Surrounding the metal-ligand cluster is a shell of predominantly hydrophobic residues from both chains of the asymmetric unit (Phe86A, Trp87A, Trp132A, Trp168A, Tyr183A, Tyr172B, Tyr173B), and both chains collaborate in the formation of a solvent-lined channel that terminates at Tyr36 and His32 near the metal ion and is presumed to be the path by which substrate or other inner-sphere ligands reach the metal.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Biol 1991 May 20
PMID:Manganese superoxide dismutase from Thermus thermophilus. A structural model refined at 1.8 A resolution. 203 60

In the reoxygenated hypoxic heart, hypoxanthine is either oxidized by xanthine oxidase with production of toxic oxygen species or salvaged for the ATP pool by hypoxanthine-guanine phosphoribosyl transferase. To characterize the repartition of hypoxanthine between the two pathways, we have subjected rat hearts to 20 min hypoxia and monitored the recovery (ventricular, end-diastolic and coronary pressures, and the contraction rate) during the reoxygenation (30 min) in the presence of either hypoxanthine or guanine alone, or both. The rate-pressure product recovered 78% of the pre-hypoxia values in hearts reoxygenated with 100 microM hypoxanthine and 80% in hearts reoxygenated with 100 microM guanine, in contrast to 49% in the presence of both hypoxanthine and guanine (100 microM each). Thus, it is likely that hypoxanthine is salvaged when present alone and is oxidized generating the reperfusion injury when the salvage is prevented by guanine that competes with hypoxanthine from the same site of hypoxanthine-guanine phosphoribosyl transferase. The functional impairment was slower when hypoxanthine was replaced by xanthine, and was eliminated by superoxide dismutase and catalase, indicating that the injury is caused by toxic oxygen species generated from hypoxanthine and xanthine oxidase. These data suggest that the salvage pathway may be critical in preventing the reperfusion injury in hypoxic hearts.
J Mol Cell Cardiol 1991 Jan
PMID:Dual role of hypoxanthine in the reoxygenation of hypoxic isolated rat hearts. 203 69

The effect of Ro 15-5458 (10-2-(diethylamino)ethyl-9-acridanone(2-thiazolin- 2-yl)hydrazone) on the steady-state RNA levels of Schistosoma mansoni was studied after dosing the host with 15 mg kg-1 and retrieving parasites. Total RNA content of parasites recovered from the host 12, 72 and 96 h after dosing was reduced by 14, 30 and 41%, respectively. Quantitative filter hybridization of blots of RNA extracted from treated and control parasites with specific probes indicated a decline in actin and superoxide dismutase mRNA as well as rRNA of treated parasites. The decline was observed 12 h after dosing, 48 h before parasites showed drug-induced changes in other vital biological processes. A prominent drug-induced reduction was seen on the 1.9 kb actin mRNA compared to the 1.4 kb. The same dose of the drug did not alter the actin mRNA content of the host liver. Similarly, the administration of the inactive structural analogue Ro 21-6787 (10-2-(diethylamino)ethyl-9-acridanone) was without any effect. We propose that the actions of Ro 15-5458 and/or its products are directed towards the inhibition of the expression of parasite genes.
Mol Biochem Parasitol 1991 Mar
PMID:The schistosomicidal compound Ro 15-5458 causes a reduction in the RNA content of Schistosoma mansoni. 205 31

We tested whether recombinant human superoxide dismutase conjugated to polyethylene glycol (PEG-SOD) to prolong its plasma retention time could limit myocardial infarct size in an ischemia-reperfusion model in the rabbit. One group of animals received 1000 units/kg of PEG-SOD as an intravenous bolus 15 min before coronary occlusion. A second group received saline only and served as controls. Under pentobarbital anesthesia, a left coronary branch was occluded for 30 min and then reperfused. The surgical wounds were repaired and the animals were allowed to recover. Seventy-two hours after the coronary occlusion, the heart was excised and the size of the area at risk (ischemic vascular bed) was assessed with fluorescent particles and the infarct size was determined by histology (Hematoxylin-eosin, Azan stain). Infarct size as a percentage of the area at risk was similar between the groups, 46.5 + 2.7 in the PEG-SOD group (n = 8) and 48.9 + 3.1 in the control group (n = 8). There were no significant differences between the groups indicating that PEG-SOD did not limit infarct size in this model.
J Mol Cell Cardiol 1991 Feb
PMID:Superoxide dismutase conjugated to polyethylene glycol fails to limit myocardial infarct size after 30 min ischemia followed by 72 h of reperfusion in the rabbit. 206 22

We examined the effect of preischemic equilibration of the rabbit heart with superoxide dismutase (SOD) on the extent of recovery of contractile function following an episode of ischemia. First, hearts were perfused with Krebs-Henseleit buffer. The pulmonary artery was cannulated and its flow diverted as the vascular effluent, and all other orifices were tied off. The fluid seeping from the epicardial surface represented the interstitial outflow. SOD was added to the perfusate and the interstitial and vascular effluents were assayed for SOD at regular intervals. Second, hearts were perfused in the Langendorff mode. SOD was included in the perfusate at all times at 20,000 U/l. After either 15 or 50 min of equilibration the hearts were subjected to 1 h of ischemia followed by 1 h of reperfusion. The developed tension was measured via a balloon in the left ventricle. Control hearts showed a recovery of developed tension of 63 +/- 12%. Human recombinant (h) Cu,Zn-SOD, which equilibrated with the interstitial fluid by 20 +/- 10% and 92 +/- 7% after 15 and 60 min of perfusion respectively, caused a recovery of 68 +/- 29% (non-significant) and 92 +/- 18% (P less than 0.01) with 15 and 50 min of equilibration respectively. The positively charged hrMn-SOD and sheep Cu,Zn-SOD, however, equilibrated much faster reaching 84 +/- 13% and 95 +/- 11% at 15 min respectively, which correlated with a recovery of 99 +/- 11% and 96 +/- 10% (P less than 0.01) respectively. HrCu,Zn-SOD conjugated to polyethylene glycol equilibrated much slower reaching 38 +/- 10% after 1 h, which correlated with lack of protection even after 50 min of equilibration. Therefore, the protection afforded by SOD to the isolated rabbit heart correlates with the concentration of SOD in the interstitial fluid. The rate of equilibration depends on the charge as well as the size of the enzyme.
J Mol Cell Cardiol 1991 Feb
PMID:Interstitial equilibration of superoxide dismutase correlates with its protective effect in the isolated rabbit heart. 206 24

The influence of membrane polyunsaturated fatty acid (PUFA) composition on lactate production, energy status, enzyme leakage and cell defences against oxygen free radical production was studied in cultured rat ventricular myocytes during hypoxia and reoxygenation. After 4 days in a conventional serum-supplemented medium, the cardiomyocytes were incubated for 24 h in synthetic media containing either linoleate and arachidonate (SM6 Medium) or linolenate and eicosapentaenoate (SM3 Medium) as unique source of PUFA. The fatty acid n-6/n-3 ratio of phospholipid was 13.1 in SM6 cells and 0.9 in SM3 cells. Hypoxia induced an increase in lactate production, severe decreases in ATP and ADP, leakage of cellular lactate dehydrogenase and reduction of superoxide dismutase and glutathione peroxidase activities. Reoxygenation of hypoxic cells reduced lactate production to normal aerobic values and allowed slight resynthesis of ATP from AMP. However, lactate dehydrogenase release was not stopped by reoxygenation, and decreases in superoxide dismutase and glutathione peroxidase activities were not avoided. The majority of the biochemical parameters measured during normoxia, hypoxia and reoxygenation were not significantly affected by changes in the fatty acid composition of membrane phospholipids, except for reduced superoxide dismutase activity which appeared earlier in SM3 cells during hypoxia. We conclude that the sarcolemmal PUFA composition of cultured rat ventricular myocytes does not significantly influence altered cell metabolism elicited by hypoxia and reoxygenation.
J Mol Cell Cardiol 1990 Oct
PMID:Influence of phospholipid polyunsatured fatty acid composition on some metabolic disorders induced in rat cardiomyocytes by hypoxia and reoxygenation. 209 39

The contribution of lung glucose-6-phosphate dehydrogenase (G-6-PD) activity to pulmonary antioxidant defenses was investigated in the isolated perfused rabbit lung using dehydroepiandrosterone (DHEA), a specific steroidal inhibitor of G-6-PD. Infusion of xanthine oxidase (0.002 U/ml) generated moderate lung edema as measured by increased lung weight and lung lavage albumin content. Infusion of DHEA caused an augmentation of xanthine oxidase-induced lung edema. Hydrostatic factors did not participate in the worsened lung edema because mean pulmonary artery pressures were similar in both experimental groups. Incubation of lung tissue in vitro with DHEA demonstrated ablation of tissue G-6-PD activity without decreasing catalase, glutathione peroxidase, or superoxide dismutase activity. It was concluded that DHEA is a specific inhibitor of lung G-6-PD, and that G-6-PD provides an important antioxidant defense mechanism in preventing oxidant-induced lung injury.
Am J Respir Cell Mol Biol 1990 Mar
PMID:Inhibition of rabbit lung glucose-6-phosphate dehydrogenase by dehydroepiandrosterone augments oxidant injury. 213 22

The human gene encoding the beta subunit of S-100 protein (S-100 beta) was mapped on chromosome 21. In order to confirm the expression of gene-dosage effect of S-100 beta in patients with Down's syndrome (DS), concentrations of immunoreactive S-100 alpha and S-100 beta proteins were determined in the blood plasma and lymphocytes fraction of the patients and control subjects. Cu/Zn-superoxide dismutase (SOD), a protein that is known to show the gene-dosage effect on the trisomy of chromosome 21, also was immunoassayed in the same blood samples as control proteins. In blood plasma, S-100 beta protein as well as Cu/Zn SOD was enhanced (P less than 0.001) in the patients (160 +/- 70 pg S-100 beta/ml and 87 +/- 83 ng SOD/ml, N = 44) as compared with control individuals (76 +/- 25 pg/ml, and 18 +/- 11 ng/ml, respectively, N = 28). However, concentrations of S-100 alpha in blood plasma of DS patients were similar to those of normal subjects. Concentrations of S-100 beta in lymphocyte fractions of DS patients (24.7 +/- 10.9 ng/mg protein) were also higher (P less than 0.001) than those of control subjects (10.1 +/- 5.8 ng/mg protein). These results indicate that gene-dosage effect of S-100 beta levels are expressed in DS patients.
J Mol Neurosci 1990
PMID:Enhancement of S-100 beta protein in blood of patients with Down's syndrome. 215 Mar 20


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