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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ATP-ADP exchange activity previously described in a membrane farction of Escherichia coli appeared after a cold osmotic shock according to Neu and Heppel ((1965) J. Biol. Chem. 240, 3685--3692) in the shock fluid. Membranes derived from shocked cells had no activity. The enzyme responsible for this activity has been purified 125-fold and catalyzed the transfer of a phosphoryl radical from ribonucleosidetriphosphates (NTPs) to ribonucleosidediphosphates (NDPs); this is, therefore, a non-specific nucleosidediphosphate kinase (ATP:nucleosidediphosphate phosphotransferase, EC 2.7.4.6). The activity required the presence of a divalent cation, Mg2+, Mn2+ or Ca2+ at a unity mol/mol ratio of nucleotide for maximal activation. The enzyme exhibited simple saturation kinetics with respect to the phosphate donor but inhibition by excess substrate was observed upon increasing phosphate acceptor. The kinetics of the reaction indicated an ordered bi-molecular ping-pong reaction mechanism. Differential heat sensitivity of the enzyme whether it is heated alone with ATP, ADP or Mg2+ opens possibilities to study different enzyme-substrate complexes.
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PMID:Nucleosidediphosphate kinase of Escherichia coli, a periplasmic enzyme. 21 26

The results of a series of experiments in the cold-preserved rat liver, applying a newly developed method of pretransplant viability testing, are described. The livers were stored either under simple hypothermic conditions (KHB) or in EC, HTK, or UW preservation solution. Livers were stored up to 48 hr and reperfused after a period of hypothermic storage of 1, 7, 14, or 21 hr. In a parallel series of experiments, with livers stored under identical conditions, repeated proton relaxometry measurements (0, 1, 7, 14, 24, 32, 48 hr) were undertaken; and ATP, ADP, AMP (Atkinson's energy charge), and water content of livers, as well as pH of storage solution, were estimated. Based on a strong correlation between proton spin-spin relaxation time T2 and tissue water content (edema), this new method may be useful to estimate the amount of cell swelling during hypothermic storage from a surgical biopsy of about 200 mg within a few minutes. There was, however, no significant correlation found between energy charge and/or pH and water content, T2, or bile flow. Our method could be useful as a rapid test method in experimental cold liver storage models and may be of interest in human liver transplantation as a viability indicator in combination with other parameters.
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PMID:Cold-preserved rat liver viability testing by proton nuclear magnetic resonance relaxometry. 131 51

The tyrosine kinase activity of the epidermal growth factor receptor (EGFR-TK) was determined at varying poly-Glu6Ala3Tyr1 (GAT) or [Val5]-angiotensin II (AT) and constant ATP concentrations and vice versa. With GAT as substrate, double reciprocal plots intersected practically on the abscissa following EGFR-TK pre-activation with EGF, but below the abscissa without EGF pre-activation. The EGFR-TK inhibitors App(NH)p (5'-adenylyl-beta, gamma-imidodiphosphate) and ADP were competitive with ATP and noncompetitive with GAT. Four families of 1/v vs. 1/[ATP] plots, constructed at different fixed concentrations of ADP and a different constant concentration of GAT for each family, yielded Slope1/ATP replots which intersected to the left of the ordinate and below the abscissa. GAT and AT, as cosubstrates, were competitive with each other and noncompetitive with ATP; 1/v vs. 1/[GAT] or 1/[AT] plots were hyperbolic and reached horizontal asymptotes when v was expressed as the rate of common product formation. All data were subjected to computer best-fit analysis by a program written especially for this purpose. We conclude that (i) the EGFR-TK reaction follows a Sequential Bi-Bi Rapid Equilibrium Random mechanism, and (ii) EGF induces conformational changes in the EGFR-TK active center which lead to marked decreases in the apparent dissociation constants of both substrates of the kinase reaction and a concomitant increase in initial velocities and Vmax (apparent).
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PMID:Kinetic model of the epidermal growth factor (EGF) receptor tyrosine kinase and a possible mechanism of its activation by EGF. 132 5

To elucidate the relationship between the high concentration of taurine in platelets and platelet aggregation in patients with EPH gestosis (gestosis with edema, proteinuria and hypertension), platelet aggregation and the platelet release response (release of ATP and beta-thromboglobulin) were studied in the washed platelet suspension (PS) obtained from normal pregnant or non-pregnant women and EPH gestosis patients. Platelet aggregation and platelet release response were significantly lower in EPH gestosis patients than in normal pregnant and non-pregnant women. Platelet aggregation, platelet release response induced by ADP and collagen and the aggregation induced by A23187 were inhibited in taurine-loaded PS from non-pregnant women. These results suggest that the decrease of platelet aggregation in EPH gestosis patients was caused by high concentrations of taurine in platelets, which may inhibit the intracellular Ca2+ movement and platelet release response. Therefore, taurine appears to have a protective effect against the hyper-coagulative state in EPH gestosis.
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PMID:Effect of taurine concentration on platelet aggregation in gestosis patients with edema, proteinuria and hypertension. 144 48

Four human ovarian and breast tumor lines expressing the HER2/neu oncogene were resistant to the cytotoxic and DNA-degradative activity of TNF. The resistance was not associated with altered TNF receptor function because Scatchard analysis of 125I-rTNF binding to HER2/neu-expressing target cells revealed receptors with normal binding parameters. Furthermore, the TNF receptors on the resistant lines were capable of signal transduction as evidence by the induction of ADP-ribose polymerase activity and MHC expression. TNF resistance was not reversed by coincubation with drugs that interrupted the glutathione redox cycle. In addition, although coincubation of HER2/neu-expressing targets with cycloheximide resulted in significant TNF-induced lysis, when compared to HER2/neu-nonexpressing targets similarly treated with cycloheximide, a significant relative resistance was still present. To investigate the role of ADP-ribosylation in the resistance of these targets, we used nontoxic concentrations of two inhibitors of ADP-ribose polymerase, 3-aminobenzamide, and nicotinamide. Both inhibitors completely reversed the resistance of HER2/neu-expressing targets to TNF-mediated cytotoxicity and DNA injury in a concentration-dependent fashion. These inhibitors of ADP-ribose polymerase did not act by down-regulating expression of HER2/neu oncogenes. In contrast, aminobenzamide and nicotinamide significantly diminished TNF-induced cytotoxicity of L929 targets. These data suggest that the activity of ADP-ribose polymerase may play a pivotal role in determining the fate of the target cell during exposure to TNF.
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PMID:Inhibitors of ADP-ribose polymerase decrease the resistance of HER2/neu-expressing cancer cells to the cytotoxic effects of tumor necrosis factor. 167 41

Patients with carotid atheromatous lesions were prospectively studied with indium-111 platelet imaging, platelet aggregability and B-mode real-time ultrasound tests to determine the short-term effects of orally active prostacyclin analogue TRK-100 (40 micrograms, three times daily for 4 weeks). To establish baseline values, all patients underwent indium-111 platelet imaging, platelet aggregation study and B-mode ultrasound. The results were positive for carotid plaque and platelet accumulation. Visual analysis showed repeated platelet scintigrams to be unchanged in five patients without antithrombotic therapy; repeated ultrasound studies showed no change in eight of ten plaques, while one showed progression and one regression of the plaque. In five TRK-100 treated patients, five of seven lesions with platelet accumulation at the baseline became negative, and two remained unchanged during the treatment; repeated B-mode ultrasound tests indicated eight of nine plaques remained unchanged, while one showed plaque size reduction. Quantitative analysis demonstrated that, TRK-100 significantly reduced the ADP aggregation (1 microM) from 55.2 +/- 21.3% to 24.0 +/- 14.7% (+/- SD; p less than 0.05) and the platelet accumulation index (25.7 +/- 17.2% vs 10.4 +/- 10.4%; p less than 0.05). However, there was no significant reduction in plaque scores during TRK-100 therapy compared with the baseline (2.70 +/- 2.75 mm vs 2.51 +/- 2.58 mm). The data obtained suggested that short-term TRK-100 therapy has an inhibitory effect on platelet accumulation in carotid atheroma but does not cause significant changes in plaque size.
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PMID:Effect of TRK-100, a stable orally active prostacyclin analogue, on platelet function and plaque size in atherothrombotic strokes. 205 14

In ischemic canine kidneys protected by Bretschneider's HTK solution the glycolytic lactate production is limited by a low renal substrate content. However, for anaerobic energy supply ischemic organs depend on glycolysis. To evaluate the role of glycolysis in renal protection, the relationship between lactate production and anaerobic energy supply was examined in protected kidneys of dogs, sheep, and swine. Additionally, in canine kidneys an attempt was made to improve anaerobic energy provision by adding glucose to the protective solution. The results were as follows: (1) According to increasing lactate production from swine to dog to sheep, intraischemic ATP decay was delayed least in swine and most in sheep. (2) Glucose addition (10 mM) to the HTK solution roughly doubled the time for ATP to fall to 1 mumol/g dry wt (tATP) in dogs. (3) The greater the lactate production in all three species, the lower the decrease in SAN (ATP + ADP + AMP) from 5 to 120 min of ischemia. (4) A glucose additive in the protective solution led to a significant (p less than .005) increase of SAN in dogs at 120 min of ischemia. A sufficient substrate supply seems to be an essential component of a reliable renal protection.
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PMID:Glucose content and efficiency of glycolysis in protected ischemic kidneys of different species. 212 43

Baraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a.8b- tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6- 1H-cyclopenta[b]benzo-furan-5-butyrate, TRK-100) is a novel stable epoprostenol (prostaglandin I2, PGI2) analogue having antiplatelet and vasodilating actions. Its effect on platelet aggregation in whole blood ex vivo and platelet suspension in vitro, formation of cyclic AMP(cAMP), production of malondialdehyde(MDA), and 45Ca++-influx into platelets were studied in rats. Oral administration of TRK-100 (0.3-1 mg/kg) showed a dose-dependent inhibition of platelet aggregation induced by ADP and collagen in whole blood and also inhibited in vitro thrombin-induced aggregation of platelet suspension in the presence or absence of external Ca++. Oral TRK-100 (0.3-3 mg/kg) dose-dependently increased plasma cAMP levels and this action was confirmed in vitro with platelet rich plasma in the presence or absence of theophylline. 45Ca++-influx into platelets stimulated by thrombin was dose-dependently inhibited by TRK-100 (3-100 nmol/l). TRK-100 (3-100 nmol/l) also suppressed MDA production induced by thrombin in platelet suspension but not that induced by arachidonic acid. From these results, TRK-100 which is orally active was suggested to exert its antiplatelet action through the increase of cAMP in platelets by activation of adenylate cyclase, concomitantly followed by the inhibition of Ca++-influx and thromboxane A2 formation.
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PMID:Studies on the antiplatelet effect of the stable epoprostenol analogue beraprost sodium and its mechanism of action in rats. 254 30

Kidneys were perfused either with Euro-Collins-solution or with HTK-solution of Bretschneider. The perfusion pressure as well as the perfusion flow were measured during a six-minute perfusion. The perfusion resistance was higher in Euro-Collins-kidneys than during HTK-perfusion. The venous outflow of the kidney as well as the ureteral outflow was measured during each minute of the perfusion and has analysed for osmolality, and for sodium and potassium concentrations. In Euro-Collins-kidneys a complete "equilibration" of the extracellular space was not achieved, while during HTK-perfusion concentrations in the venous as in the tubular outflow, similar to those in the HTK-solution itself, could be reached. At the end of the different perfusions, tissue was analysed for biochemical parameters such as ATP, ADP, AMP and lactate as well as for morphological features. Lactate had increased and ATP had decreased during perfusion with Euro-Collins-solution, while ATP had not changed and lactate had decreased during perfusion with HTK-solution. Normal glomerular, tubular and dilated vascular structures can be seen after HTK-perfusion, while a glomerular and vascular contraction takes place during Euro-Collins-perfusion.
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PMID:Short-term perfusion and "equilibration" of canine kidneys with protective solutions. 310 3

Long-term preservation of dog hearts was performed over 24 h using Bretschneider-HTK cardioplegia and cold storage. Preservation was assessed in terms of conservation of myocardial tissue levels of high-energy phosphates (HEP) and functional outcome after cardiac transplantation. Serial left ventricular biopsies were taken and analysed for ATP, ADP, AMP, adenosine, inosine, hypoxanthine, xanthine and creatine phosphate. Myocardial structure was studied by electron microscopical examination of a similar biopsy specimen. Cardiac performance was measured before and after cardiac transplantation. Several techniques of cardioplegic arrest were studied: single dose cardioplegia, multidose cardioplegia and continuous perfusion with the cardioplegic solution. In all groups, the hearts were stored at 0.5 degree C for 24 h. In the group of single dose Bretschneider-HTK cardioplegia, myocardial ATP content after 24 h of cold storage was only 25% of control. The total sum of nucleotides at that time interval was however 65% of the control value. Reperfusion of these hearts using a support dog (whole blood reperfusion) did not result in any recovery of ATP. Creatinine phosphate however showed an overshoot. Accumulated nucleosides were washed out. The hearts showed electrical activity but were severely arrhythmic. Contractility was poor. In the group of multidose Bretschneider-HTK cardioplegia, HEP preservation was better than after single dose cardioplegia. ATP content was about 50% of control. The total sum of nucleotides was 85% of control. Ultrastructural assessment of the myocytes revealed only slight ischaemic damage to the mitochondria. Reperfusion on cardiopulmonary bypass after cardiac transplantation did not show any restoration of ATP, but a steady catabolism of HEP. The nucleosides adenosine and inosine were not washed out upon reperfusion. After cardiac transplantation, none of these hearts could be weaned from cardiopulmonary bypass due to irreversible low cardiac output. Histological examination demonstrated irreversible myocardial tissue damage. In the group of continuous cold Bretschneider cardioplegia, HEP content was completely preserved throughout the 24 h of perfusion. Ultrastructure of the myocytes was normal. Reperfusion of the transplanted hearts showed a mild breakdown of ATP to 70% of control values accompanied by a slight accumulation of nucleosides. Haemodynamic recovery however was perfect and none of the hearts needed positive inotropic support. Myocytes after reperfusion had a normal subcellular appearance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Energy state of the myocardium during long-term cold storage and subsequent reperfusion. 327 28


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