Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study used transient transfection analysis to determine the DNA regions which mediate basal and insulin-sensitive transcription from the gene encoding tyrosine aminotransferase (TAT; EC 2.6.1.5). Basal expression requires at least parts of two regions: a region at -3600 and a region from -208 to + 62. Insulin sensitivity requires at least one region of the promoter not required for basal expression. Thus, insulin cannot act solely by direct modification of any of the components required for basal transcription. Previous results from this laboratory suggest that the insulin effects on basal and glucocorticoid-induced TAT transcription require different regions of the proximal promoter.
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PMID:Insulin-responsive tyrosine aminotransferase transcription requires multiple promoter regions. 135 38

Insulin-mediated regulation of glucocorticoid-induced expression of the liver-specific gene tyrosine aminotransferase was studied in a clone of the Reuber rat hepatoma cells. Insulin inhibited dexamethasone-induced chloramphenicol acetyltransferase expression from approximately 4 kb of TAT 5' flanking sequence. The degree of this inhibition was comparable to the response of the endogenous gene. A construct of approximately 3 kbp of 5' flanking sequence exhibited no significant basal expression but retained sensitivity to glucocorticoids and to insulin inhibition of the glucocorticoid response. Results of further analysis of the insulin response in deletion constructs and constructs containing glucocorticoid responsive elements ligated to a heterologous promoter suggest that in addition to the glucocorticoid response elements a region close to the start site in the TAT promoter is necessary for insulin to inhibit glucocorticoid-mediated induction of expression.
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PMID:Insulin-mediated inhibition of the induction of tyrosine aminotransferase by dexamethasone. 135 29

One hundred and fourty-eight insulin-dependent diabetic patients were available for this study; 56 males and 92 females. For the investigation of coagulation activation we determined activated partial thromboplastin time, thrombin time, and fibrinogen besides fibrin monomers and thrombin-antithrombin III complexes (TAT-III). We assessed large percentages of increased fibrinogen levels but non-significant increases of the mean values in comparison with the reference group. The values for thrombin time were significantly prolonged, although relatively small percentages were exceeding the reference range. For the activated partial thromboplastin time, the values exceeded the upper reference limit, and the mean values were significantly higher than those of the reference group. Also for the fibrin monomers we obtained often enhanced values, and moreover, the values were significantly higher as compared with the reference subjects. The amount of TAT-III concentrations above the reference range was much smaller than for the fibrin monomers and the TAT-III levels were not significantly enhanced. The results presented here are indicative of coagulation activation in diabetics, as indicated by the fibrin monomers and more or less by the TAT-III levels. Moreover, there could be demonstrated a positive correlation between fibrin monomer levels and HbA1 concentrations.
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PMID:Coagulation activation in diabetes mellitus. 228 7

The effect of insulin on the abundance of mRNAs coding for tyrosine aminotransferase (TAT; EC 2.6.1.5), tryptophan oxygenase (TO; EC 1.13.1.12), and P-enolpyruvate carboxykinase(GTP) (PEPCK; EC 4.1.1.32) was examined in primary cultures of adult rat hepatocytes and in FTO-2B rat hepatoma cells by Northern blot analysis using RNA probes made from SP6-cDNAs. Insulin (10(-11)-10(-7) M), which has been reported to induce TAT and decrease the activity of TO, did not change the levels of TAT mRNA and TO mRNA in hepatocytes regardless of the presence of other inducers. In the same cells, dexamethasone increased TAT mRNA up to 19-fold and TO mRNA up to 15-fold, and 8pClPhS-cAMP (CPT-cAMP) raised the level of TAT mRNA up to 36-fold. The abundance of TO mRNA was not altered by CPT-cAMP. In contrast to TAT mRNA and TO mRNA, the level of PEPCK mRNA was dramatically decreased by insulin in the same hepatocytes. The sensitivity to this inhibitory effect of insulin was enhanced by dexamethasone and reduced by CPT-cAMP. FTO-2B hepatoma cells, which do not express detectable levels of TO mRNA, showed responses similar to those of hepatocytes, except that insulin caused a moderate reduction in TAT mRNA, but only in the presence of CPT-cAMP. The PEPCK mRNA in FTO-2B cells was suppressed by insulin in a manner closely resembling the effects in hepatocytes in the present study and in H4IIE hepatoma cells previously reported.
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PMID:Regulation of gene expression in rat hepatocytes and hepatoma cells by insulin: quantitation of messenger ribonucleic acid's coding for tyrosine aminotransferase, tryptophan oxygenase, and phosphoenolpyruvate carboxykinase. 287 68

Of all available liver cells in culture, only primary cultured hepatocytes are known to respond to glucagon in vitro. In the present study we investigated whether glucagon could stimulate amino acid transport and tyrosine aminotransferase (TAT;EC 2.6.1.5) activity (two well-characterized glucagon effects in the liver) in Fao cells, a highly differentiated rat hepatoma cell line. We found that glucagon had no effect on transport of alpha-aminoisobutyric acid (AIB; a non-metabolizable alanine analogue) nor on TAT activity, even though both activities could be fully induced by insulin [2-fold and 3-fold effects for AIB transport and TAT activity, respectively, after 6h; EC50 (median effective concentration) = 0.3 nM], or by dexamethasone (5-8-fold effects after 20 h; EC50 = 2 nM). Analysis of [125I]iodoglucagon binding revealed that Fao cells bind less than 1% as much glucagon as do hepatocytes, whereas insulin binding in Fao cells was 50% higher than in hepatocytes. The addition of dibutyryl cyclic AMP, which fully mimics the glucagon stimulation of both AIB transport and TAT activity in hepatocytes, induced TAT activity in Fao cells (a 2-fold effect at 0.1 mM-dibutyryl cyclic AMP) but had no effect on AIB transport. Cholera toxin stimulated TAT activity to the same extent as did dibutyryl cyclic AMP. These results indicate that the lack of glucagon responsiveness in cultured hepatoma cells results from both a receptor defect and, for amino acid transport, an additional post-receptor defect. Moreover, the results show that amino acid transport and TAT activity, which appeared to be co-induced by insulin or by dexamethasone in these cells, respond differently to cyclic AMP. This suggests that different mechanisms are involved in the induction of these activities by glucagon in liver.
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PMID:Glucagon resistance of hepatoma cells. Evidence for receptor and post-receptor defects. 613 31

The dispase perfusion technique was used to isolate liver cells from adult rats. The optimum conditions for obtaining many isolated liver cells with high viability were an enzyme concentration of 2000 U/ml, a pH of 7.5 and a perfusion time of 20 min. The population of isolated liver cells prepared with dispase consisted of 43.6% cells with diameters less than 20 micron and 56.4% cells with diameters above 20 micron. The isolated liver cells were cultured in basal culture medium either supplemented with or without dexamethasone (1 X 10(-5)M) and insulin (10 micrograms/ml). The addition of hormones to the culture medium improved the attachment efficiency of the isolated liver cells and delayed the disappearance of mature hepatocytes. Epithelial-like clear cells proliferated early in primary culture even in the presence of hormones. Therefore, functioning mature hepatocytes and proliferating epithelial-like clear cells coexisted well in the hormone-containing medium. Furthermore, the number of cultured cells reached a maximal level earlier in the presence of hormones than in the absence of hormones. The level of TAT activity in primary cultured cells was higher up to 3 days after inoculation in the presence of hormones than in their absence. No difference between G6Pase activity in primary cultured cells in the presence of hormones and that in the absence of hormones was found.
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PMID:Preparation and primary culture of liver cells isolated from adult rats by dispase perfusion. 614 68

Primary cultures of liver cells isolated from adult rats by trypsin and collagenase perfusion techniques were carried out to compare cytologic and biochemical properties between the differently prepared cells. Trypsin-dispersed cells consisted of comparatively smaller cells, whereas collagenase-dispersed cells consisted of larger cells. The cell attachment efficiency on culture day 1 was about twice as high in the liver cells prepared with collagenase than those prepared with trypsin. Mature hepatocytes isolated by collagenase perfusion could be maintained in the primary culture for a longer period than those isolated by trypsin perfusion. Epithelial-like clear cells started to grow much earlier in the primary culture of the trypsin-dispersed liver cells than in that of the collagenase-dispersed liver cells. Earlier proliferation of epithelial-like clear cells could not be induced by in vitro trypsinization of the collagenase-dispersed liver cells. Both kinds of enzymatically prepared liver cells showed albumin production and exhibited glucose 6-phosphatase (D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9, G6Pase) and tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate amino-transferase, EC 2.6.1.5, TAT) activities for 1 week in the primary culture. Albumin production was higher in the liver cells prepared with collagenase than those prepared with trypsin, whereas G6Pase activity was almost the same between them. TAT activity up to culture day 2 was about 3-fold higher in the liver cells prepared with collagenase than in those prepared with trypsin. Combined supplementation of dexamethasone (1 X 10(-5)M) and insulin (10 micrograms/ml) consistently improved the cell attachment efficiency and was very effective in the maintenance of mature hepatocytes in both types. Furthermore, these hormones enhanced the albumin production and TAT activity in both types.
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PMID:Comparison of cytologic and biochemical properties between liver cells isolated from adult rats by trypsin perfusion and those isolated by collagenase perfusion. 614 85

Dexamethasone induces TAT in the embryonic chick liver, but this effect is not blocked by prior administration of insulin at a dose sufficient to increase the hepatic protein/DNA ratio. Similarly, insulin does not block dexamethasone induction of TAT in chick embryo hepatocytes in vitro. In contrast, insulin reduces TAT induction by dexamethasone in fetal rat hepatocytes by 35-40%. No significant differences in insulin binding were noted between chick and rat hepatocytes.
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PMID:Insulin inhibition of tyrosine aminotransferase induction by dexamethasone is species-related. 614 50

An immunocytochemical analysis of hormonal status of transgenic rats containing human growth hormone gene has been done. The enhanced expression of the endogenous growth hormone gene was demonstrated with poly- and monoclonal antibodies inside somatatropes of pituitary. No activity of the heterologous growth hormone gene was revealed in kidney, pancreas or liver as it might be expected according to specificity of MT1 and TAT promotors. Transgenic animals of F0, F1 and F2 generation exhibited disturbance of functional morphology of glucagon and insulin producing cells. Lymphocyte infiltration was found in pancreatic islets. The transgenic rabbits and swine with the gene of releasing factor of human growth hormone did not reveal any severe disturbance. Although one swine demonstrated alterations in glucagon producing cells and one rabbit revealed a disturbed morphology of the stomach tissues. The data are discussed in relation to general problems of transgene activity and interaction with endogenous homolog.
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PMID:[An immunocytochemical analysis of the hormonal status of animals transgenic for growth hormone genes and for a mini-gene of human growth hormone-releasing factor]. 780 75

The pathway of gluconeogenesis is activated in liver shortly after birth and is controlled by glucagon and glucocorticoids, which stimulate, and insulin, which inhibits, the expression of genes coding for gluconeogenic enzymes. To understand the molecular basis of this cell type-specific and coordinate control, we analyzed the cis-regulatory elements of the tyrosine aminotransferase gene, which confer liver cell-specific expression in dependence of these hormones. The cAMP-responsive element (CRE) of the TAT gene is an essential element within a liver-specific enhancer and is recognized by the CRE-binding protein (CREB) in a phosphorylation-dependent manner. The glucocorticoid response is mediated by a complex regulatory unit comprised of the glucocorticoid receptor and other transcription factor-binding sites. Here, we show that both the cAMP- and glucocorticoid-inducible enhancers are targets for the antagonistic effects of insulin. The insulin-responsive sequences coincide with the CREB-binding site of the cAMP-responsive enhancer and a hepatocyte nuclear factor-3-binding site within the glucocorticoid-responsive unit. This design of the hormone-dependent enhancers reflects the molecular mechanism underlying the onset of tyrosine aminotransferase expression at birth when insulin levels decrease and concentrations of glucagon and glucocorticoids increase.
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PMID:The cyclic adenosine 3',5'-monophosphate- and the glucocorticoid-dependent enhancers are targets for insulin repression of tyrosine aminotransferase gene transcription. 798 51


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