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81.
Heparin and ionic strength-dependent conversion of antithrombin III from an inhibitor to a substrate of alpha-thrombin 总被引:6,自引:0,他引:6
S T Olson 《The Journal of biological chemistry》1985,260(18):10153-10160
The stoichiometry of antithrombin III (AT) inhibition of alpha-thrombin (T) has been investigated in the presence and absence of heparin as a function of ionic strength by quantitative titration of enzyme active sites. In contrast to the ionic strength-independent stoichiometry of 1.0 mol of AT/mol of T observed in the absence of heparin, the presence of high-affinity heparin (HAH) resulted in an ionic strength-dependent increase in the apparent stoichiometry of inhibition from a molar ratio of 1.1 AT/T at an ionic strength of 0.3 to 9.8 mol of AT/T when the ionic strength was lowered to 0.01. Reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the reaction products revealed that the increased AT/T stoichiometry was due to preferential formation of a specific proteolytically cleaved form of AT that was indistinguishable from the previously characterized reactive site-cleaved AT (ATM). Using high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to quantitate ATM, the cleaved inhibitor was shown to be formed rapidly and concomitant with the stable thrombin-antithrombin complex (TAT) and quantitatively accounted for the apparent increase in reaction stoichiometry at low ionic strength in the presence of HAH. The levels of HAH required to produce maximum ATM were catalytic at mu greater than or equal to 0.15, but became stoichiometric as the ionic strength decreased below 0.1. Substantially less ATM was produced in the presence of low-affinity heparin, while a low molecular weight HAH, virtually inactive in accelerating T inhibition by AT, was unable to promote significant ATM formation. These results indicate competition between substrate and inhibition reactions of AT with T which are affected by an ionic strength-dependent heparin interaction. A reaction mechanism accounting for these observations is proposed. 相似文献
82.
Abstract We tested the hypothesis that electrogenic ion pumps, working at the parenchyma symplast/xylem interface of pea hypocotyls, provide the driving force for K+ uptake from the xylem. Solutions of known composition were perfused through a hypocotyl segment. The K+ activity of the solution flowing out of the xylem (K+out) increased (i.e. K+ uptake decreased) when aerobic respiration was inhibited by lack of O2, and this was preceded by a decrease in Vpx (electrical potential difference between parenchyma symplast and xylem). Perfusion with auxin (1AA) and fusicoccin (FC) stimulated the electrogenic activity of the ‘xylem pumps’ (111 and 205% respectively) and stimulated uptake of K + from the xylem (with 71% and 29% respectively). The close correlation between xylem pump activity and K+ uptake corroborated the aforementioned hypothesis. Interestingly, inhibition of pump activity by anoxia was incomplete in the presence of FC. It is thought that FC increases the affinity of the ATP-requiring xylem pump for ATP, thus ensuring that ATP production during fermentation is sufficient to fuel the pump in the absence of O2. 相似文献
83.
Eight isolates of Naegleria australiensis were obtained from a small lake in Tulsa, Oklahoma. The eight strains were isolated during the hot summer months of July through September, when water temperatures ranged from 27 to 33°C. All eight isolates were pathogenic for mice. The mean time to death for mice was 10 days (range 6–13 days). This pathogenic free-living ameba has not before been reported from the United States or the Western Hemisphere. 相似文献
84.
We studied the porcine pulmonary response to endotoxemia before and after administration of nonsteroidal antiinflammatory drugs (NSAID, i.e., indomethacin or flunixin meglumine) or dexamethasone (DEX). Escherichia coli endotoxin was infused intravenously into anesthetized 10- to 12-wk old pigs for 4.5 h. In endotoxemic pigs, the phase 1 (i.e., 0-2 h) increases in pulmonary arterial pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient and the decreases in cardiac index (CI) and lung dynamic compliance (Cdyn) were blocked by NSAID. Thus phase 1 changes were cyclooxygenase dependent. Furthermore, these effects were blocked or greatly attenuated by DEX. During phase 2 of endotoxemia (i.e., 2-4.5 h), the increased PVR and decreased CI and Cdyn were not blocked by NSAID but were attenuated by DEX, suggesting the presence of cyclooxygenase-independent metabolites. Both NSAID and DEX blocked the endotoxin-induced increases in lung water, bronchoalveolar lavage (BAL) neutrophil, and BAL albumin content. The fall in plasma proteins persisted in NSAID but not DEX-treated pigs. We conclude that endotoxemia in the pig causes severe acute respiratory failure largely mediated by cyclooxygenase and possibly lipoxygenase products of arachidonic acid metabolism. 相似文献
85.
D B Buxton S D Shukla D J Hanahan M S Olson 《The Journal of biological chemistry》1984,259(3):1468-1471
1-O-Alkyl-2-acetyl-sn-glyceryl 3-phosphorylcholine or acetylglyceryl ether phosphorylcholine (AGEPC) stimulated glycogenolysis in perfused livers from fed rats at concentrations as low as 10(-11) M. At the lower AGEPC concentrations, e.g. 2 X 10(-10) M, a single transient phase of enhanced hepatic glucose output was elicited upon infusion of this agonist. At higher concentrations, e.g. 2 X 10(-8) M, a sharp transient spike of glucose output was observed, followed by a stable elevated steady state rate of glucose output until the AGEPC infusion was terminated. Increased rates of lactate and acetoacetate output and a diminished hepatic oxygen consumption were characteristic of the response of the livers to AGEPC at 2 X 10(-10) M. Neither alpha- nor beta-adrenergic antagonists blocked the glycogenolytic response of AGEPC. Repeated infusion of AGEPC led to homologous desensitization of the response, but the response of the liver to the alpha-adrenergic agonist, phenylephrine, or to glucagon, subsequent to AGEPC stimulation, was unaffected. Increasing the period of perfusion between successive additions of AGEPC, from 7 to 30 min, resulted in an increased glycogenolytic response to this agonist. When the perfusate calcium concentration was reduced from 1.25 to 0.05 mM, the glycogenolytic response to AGEPC was markedly diminished; calcium efflux from the liver following stimulation with AGEPC was not observed. The data presented in this study illustrate a potent agonist effect of AGEPC on the glycogenolytic system in the rat liver. 相似文献
86.
Changes in the concentration of progesterone, estrone, estradiol, prostaglandins (PG) E2, 6-keto F1 alpha and 13,14-dihydro-15-keto F2 alpha (PGFM) were measured in peripheral plasma, and in venous effluent from the shell gland and the largest (F1) and the second largest (F2) preovulatory follicles. Tissue concentrations in the F1, F2 and the most recently ruptured follicle and the shell gland also were determined. Changes in these criteria were compared to changes in uterine contraction before the first ovulation of a sequence. Significant increases of PGF2 alpha and PGFM in the peripheral plasma were observed when the frequency of uterine contraction reached a maximum, about 1 h before ovulation. Relative to peripheral plasma, the concentrations in F1 plasma of progesterone, PGF2 alpha and PGFM were increased 20-fold, 150-fold and 15-fold, respectively, at the time of the maximum frequency of uterine contraction. The highest tissue concentrations of PGs were also observed in the F1 follicle. These results suggest that the largest preovulatory follicle is the major source of PG synthesis and release. These PGs may stimulate uterine contraction and may also play a role in follicular rupture and release of the ovum. 相似文献
87.
Potentiation of dimethylnitrosamine genotoxicity in rat hepatocytes isolated following ethanol treatment in vivo 总被引:1,自引:0,他引:1
Michael J. Olson Joel G. Pounds Daniel A. Casciano 《Chemico-biological interactions》1984,50(3):313-326
Unscheduled DNA synthesis (UDS), following exposure to dimethylnitrosamine (DMN), was potentiated in cultured hepatocytes isolated following treatment of rats for 14 or 28 days with 20% ethanol/5% sucrose solution. Ethanol treatment was associated with increased UDS, a concomitant increase in hepatic microsomal protein concentration and DMN N-demethylase activity. Increased aniline hydroxylase activity of hepatic microsomes from ethanol-treated rats preceded the measured increase in microsomal protein content or DMN metabolism. The increase in metabolism of DMN in vitro and potentiation of DMN-induced UDS associated with ethanol treatment may contribute to a synergistic effect of ethanol on DMN hepatotoxicity and carcinogenicity. In contrast, ethanol pretreatment did not increase the cytotoxicity of DMN as characterized by enzyme release. 相似文献
88.
The stimulation of hepatic gluconeogenesis by acetoacetate precursors. A role for the monocarboxylate translocator 总被引:1,自引:0,他引:1
The regulation of the gluconeogenic pathway from the 3-carbon precursors pyruvate, lactate, and alanine was investigated in the isolated perfused rat liver. Using pyruvate (less than 1 mM), lactate, or alanine as the gluconeogenic precursor, infusion of the acetoacetate precursors oleate, acetate, or beta-hydroxybutyrate stimulated the rate of glucose production and, in the case of pyruvate (less than 1 mM), the rate of pyruvate decarboxylation. alpha-Cyanocinnamate, an inhibitor of the monocarboxylate transporter, prevented the stimulation of pyruvate decarboxylation and glucose production due to acetate infusion. With lactate as the gluconeogenic precursor, acetate infusion in the presence of L-carnitine stimulated the rate of gluconeogenesis (100%) and ketogenesis (60%) without altering the tissue acetyl-CoA level usually considered a requisite for the stimulation of gluconeogenesis by fatty acids. Hence, our studies suggest that gluconeogenesis from pyruvate or other substrates which are converted to pyruvate prior to glucose synthesis may be limited or controlled by the rate of entry of pyruvate into the mitochondrial compartment on the monocarboxylate translocator. 相似文献
89.
Valyl-tRNA synthetase modification-dependent restriction of bacteriophage T4 总被引:2,自引:1,他引:1
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A strain of Escherichia coli, CP 790302, severely restricts the growth of wild-type bacteriophage T4. In broth culture, most infections of single cells are abortive, although a few infected cells exhibit reduced burst sizes. In contrast, bacteriophage T4 mutants impaired in the ability to modify valyl-tRNA synthetase develop normally on this strain. Biochemical evidence indicates that the phage-modified valyl-tRNA synthetase in CP 790302 is different from that previously described. Although the enzyme is able to support normal protein synthesis, a disproportionate amount of phage structural protein (serum blocking power) fails to mature into particles of the appropriate density. The results with host strain CP 790302 are consistent with either a gratuitous inhibition of phage assembly by faulty modification or abrogation of an unknown role that valyl-tRNA synthetase might normally play in viral assembly. 相似文献
90.
MAURÍLIO JOS SOARES MARCOS FARINA DE SOUZA WANDERLEY DE SOUZA 《The Journal of eukaryotic microbiology》1987,34(2):199-203
An imidazole-buffered osmium tetroxide solution was used to visualize lipids at the ultrastructural level in the following members of the family Trypanosomatidae: Trypanosoma cruzi, T. dionisii, T. vespertilionis, T. rangeli, Crithidia deanei, C. fasciculata, C. oncopelti, and Blastocrithidia culicis. Electron-dense material was seen in various lipid droplets found in all parasites and in the multivesicular structure of members of the sub-genus Schizotrypanum. High contrast of some membranes, mainly those which enclose the mitochondrion, the nucleus, and the endoplasmic reticulum, was observed even in unstained sections. X-ray microanalysis confirmed that the electron density of lipid droplets of B. culicis and membrane-bounded dense granules of C. oncopelti was due to the presence of osmium. 相似文献