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We have previously shown that 3,5,3'-triiodo-L-thyronine (L-T3) stimulates cell growth and a 4- to 8-fold increase in growth hormone mRNA in GH1 cells. These effects appear to be mediated by a thyroid hormone nuclear receptor with an equilibrium dissociation constant for L-T3 of 0.2 nM and an abundance of about 10,000 receptors per cell nucleus. In this report, we show that L-T3 exerts a pleiotypic effect on GH1 cells to rapidly (within 2 h) stimulate [3H]uridine uptake to a maximal value of 2.5- to 3-fold after 24 h. This results from an increase in the number of functional uridine "transport sites" as shown by studies documenting an increase in the apparent Vmax with no change in the Km, 17 microM. Although the labeling of the cellular uridine pool and pools of all phosphorylated uridine derivatives was increased by L-T3, there was no change in the relative amounts of the individual pools in cells incubated with or without hormone. The intracellular concentration of [3H]uridine was estimated to be similar to that of the medium, suggesting that facilitated transport mediates [3H]uridine uptake. That this increase in [3H]uridine transport was nuclear receptor-mediated is supported by the excellent correspondence of the L-T3 dose-response curve for [3H]uridine uptake and that for L-T3 binding to receptor. Finally, inhibition of protein synthesis by cycloheximide and RNA synthesis by actinomycin D demonstrated that the L-T3 effect required continuing protein and RNA synthesis. These results are consistent with an effect of the L-T3-nuclear receptor complex to increase uridine uptake in GH1 cells by altering the expression of gene(s) essential for the transport process. 相似文献
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Isolated rat lungs, pretreated with 100 microM pargyline and 100 microM U-0521 (3',4'-dihydroxy-2-methylpropriophenone) to block metabolism of norepinephrine (NE), were perfused with 0.3 microM 3H-labeled l-norepinephrine (1-[3H]-NE) for 30 min. Efflux samples were then collected for 30 min during washout of the tissue with amine-free Krebs solution. Compartmental analysis (nonlinear least-squares regression) of the efflux of tissue l-[3H]NE content vs. time indicates that NE is accumulated in a large slowly equilibrating compartment (t 1/2 = 58.15 +/- 6.84 min) in addition to distribution in the vascular (blue dextran tracer) and extracellular ([3H]sorbitol tracer) fluid compartments of the lung. Pretreatment of the lungs with 100 microM cocaine hydrochloride reduces the total l-[3H]NE space from 7.44 +/- 1.91 to 2.48 +/- 0.23 ml/g (P less than 0.05) by selectively decreasing the size of the slow NE compartment from 6.99 +/- 1.97 to 1.67 +/- 0.14 ml/g (P less than 0.05). The large size, cocaine sensitivity, and long efflux half time of this compartment suggest that neuronal uptake contributes to the pulmonary vascular inactivation of l-[3H]NE. 相似文献
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We have proposed that glutamine serves in a facilitated diffusion process, mediated by the enzyme gamma-glutamyl transferase (gamma-glutamyl transpeptidase; gamma GT) and that it leaves the brain in exchange for entering amino acids. Glutamine is also a precursor of gamma-aminobutyric acid (GABA). Thus, providing an alternate substrate for gamma GT should spare brain glutamine, raise GABA, and cause an anticonvulsant effect. We have found that glycylglycine, the best-known substrate for gamma GT, and delta-aminovaleric acid (DAVA), a structural analog, have anticonvulsant activity in DBA/2J mice. Both compounds can decrease the incidence and severity of seizures induced by L-methionine-RS-sulfoximine or electroconvulsive shock. DAVA was also tested and found to be active against seizures caused by pentylenetetrazol or picrotoxin. [14C]DAVA entered the brain at the rate of 18.7 nmol/g/min. The activity of DAVA as a substrate of gamma GT was intermediate to that of glycylglycine and glutamine. Preliminary studies have shown that brain glutamine and perhaps GABA are elevated 3 h after administration of DAVA (7.5 mmol/kg). These findings support the theory that glutamine exchange plays a role in amino acid transport across the blood-brain barrier and suggests a new concept in anticonvulsant therapy. 相似文献
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Immunoenzymological Evidence Suggesting a Change in Conformation of Adenylic Acid Deaminase and Creatine Kinase during Substrate Combination 总被引:1,自引:0,他引:1 下载免费PDF全文
Arthur J. Samuels 《Biophysical journal》1961,1(6):437-444
The kinetics of inhibition of 5′-adenylic acid deaminase and creatine-ATP transphosphorylase by their respective antibodies are studied and rate constants of combination are ascertained. It is shown that the single substrate 5′-adenylic acid (AMP) of deaminase “protects” the enzyme against antibody inhibition. However, phosphate, a competitive inhibitor of the highly specific deaminase, enhances combination with antibody. With creatine kinase, however, addition of either of the substrates, alone or in combination with the required magnesium, each of which separately bind to the enzyme, does not prevent inhibition of the enzyme by its antibody. However, the “working” enzyme combined with all substrates is “protected” against antibody inhibition. 相似文献
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Analysis of linear plasmid dimers in Borrelia burgdorferi sensu lato isolates: implications concerning the potential mechanism of linear plasmid replication. 总被引:4,自引:1,他引:3 下载免费PDF全文
The Borrelia genome is composed of a linear chromosome and a number of variable circular and linear plasmids. Atypically large linear plasmids of 92 to 105 kb have been identified in several Borrelia burgdorferi sensu lato isolates and characterized. These plasmids carry the p27 and ospAB genes, which in other isolates reside on a 50-kb plasmid. Here we demonstrate that these plasmids are dimers of the 50-kb ospAB plasmid (pAB50). The 94-kb plasmid from isolate VS116, pVS94, was an exception and did not hybridize with any plasmid gene probes. When this plasmid was used as a probe, homologous sequences in other isolates were not detected, suggesting that it is unique to isolate VS116. These analyses provide insight into the mechanism of linear plasmid replication and the mechanisms by which plasmid variability can arise. 相似文献
8.
Genetic transformation of the Lyme disease agent Borrelia burgdorferi with coumarin-resistant gyrB. 总被引:12,自引:8,他引:4 下载免费PDF全文
No useful method to genetically manipulate Borrelia burgdorferi, the causative agent of Lyme disease, has been developed previously. We have used resistance to the coumarin antibiotic coumermycin A1, an inhibitor of DNA gyrase, as a genetic marker to monitor the transformation of B. burgdorferi by electroporation. Introduction of site-directed mutations into the gyrB gene demonstrated that transformation was successful, provided evidence that homologous recombination occurs on the chromosome, and established that mutations at Arg-133 of DNA gyrase B confer coumermycin A1 resistance in B. burgdorferi. The coumermycin A1-resistant gyrB marker and genetic transformation can now be applied toward dissecting the physiology and pathogenesis of the Lyme disease agent on a molecular genetic level. 相似文献
9.
The conserved ninth C-terminal heptad in thyroid hormone and retinoic acid receptors mediates diverse responses by affecting heterodimer but not homodimer formation. 总被引:18,自引:11,他引:7 下载免费PDF全文
M Au-Fliegner E Helmer J Casanova B M Raaka H H Samuels 《Molecular and cellular biology》1993,13(9):5725-5737
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