Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tyrosine aminotransferase (TAT) induction by glucagon and dexamethasone in the liver of tumor-bearing chickens was studied and compared with induction in healthy animals. The transplantable tumor was caused by inoculation of cells from a cell line induced by MC29 avian leukosis virus. TAT was hardly detectable in tumor tissue of control and dexamethasone-treated chickens, but it was induced by glucagon to levels which were significant although very low when compared to those in host liver or the liver of non-tumor-bearing controls after glucagon treatment. Dexamethasone failed to induce TAT in host liver at 8 A.M. while it significantly indiced TAT in the normal liver at the same time of the day. Similar failure of TAT induction was not detectable when glucagon was used instead of dexamethasone. Furthermore, it was found that diurnal variations in basal and dexamethasone or glucagon-induced TAT levels are considerably mitigated in host liver as compared to those observed in the liver of healthy animals. The possible reasons for these findings are discussed.
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PMID:Tyrosine aminotransferase induction in normal and tumor-bearing chickens. 0 Mar 37

Tyrosine aminotransferase mRNA was quantitated by translation in a cell-free system derived from wheat germ followed by specific immunoprecipitation of the newly synthesized enzyme subunit. Hepatic poly(A)-containg RNA prepared from rats treated for 4 h with N6, O2'-dibutyryl cyclic AMP and theophylline was approximately 5.6 times more active in directing the synthesis of the tyrosine aminotransferase subunit relative to untreated controls. The overall template activity of the RNA prepared from control and cyclic AMP-treated animals was virtually identical, demonstrating that the cyclic nucleotide effect was specific for the tyrosine aminotransferase mRNA. At all times, after a single injection of dibutyryl cyclic AMP and theophylline, the increase in hepatic enzyme activity was accompanied by corresponding induction in the level of functional tyrosine aminotransferase mRNA. Other inducers of tyrosine aminotransferase, such as glucagon and hydrocortisone, also increased the level of tyrosine aminotransferase mRNA in proportion to their effect on enzyme activity. The RNA polymerase II inhibitor, alpha-amanitin, completely blocked the dibutyryl cyclic AMP-mediated increase in tyrosine aminotransferase mRNA activity. These studies demonstrate that, in intact animals, the induction of tyrosine aminotransferase activity by dibutyryl cyclic AMP can be completely accounted for by a corresponding increase in the level of functional mRNA coding for the enzyme.
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PMID:Increase in hepatic tyrosine aminotransferase mRNA during enzyme induction by N6,O2'-dibutyryl cyclic AMP. 2 49

Tyrosine aminotransferase activity in rat liver increases during the first 24 hrs after partial hepatectomy with two peaks, one at 10 hrs and another at 18 hrs. This behaviour is due to an increase in TATmRNA synthesis. Expression of serine deydratase is also enhanced during the first 5 hrs after hepatectomy. It is suggested that the enhanced expression of the two genes is due to an increase in hormone incretion particularly glucagon and glucocorticoids.
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PMID:Different expression of tyrosine aminotransferase and serine deydratase in rat livers after partial hepatectomy. 137 Aug 91

1. The administration of glucagon, cAMP [adenosine 3',5'-(cyclic)-monophosphate], BcAMP [6-N-2'-O-dibutyryladenosine 3',5'-(cyclic)-monophosphate] or adrenaline to foetal rats during the last 2 days of gestation evoked the appearance of tyrosine aminotransferase and enhanced the accumulation of glucose 6-phosphatase in the liver. In foetuses 1-2 days younger only BcAMP was effective. After birth liver glucose 6-phosphatase no longer responds to glucagon or BcAMP. Tyrosine aminotransferase is still inducible by these agents in 2-day-old rats, but not in 50-day-old rats. After adrenalectomy of adults glucagon or BcAMP can enhance the induction of the enzyme by hydrocortisone. The results indicate that the ability to synthesize tyrosine aminotransferase and glucose 6-phosphatase when exposed to cAMP develops sooner than the ability to respond to glucagon with an increase in the concentration of cAMP; the responsiveness of enzymes to different hormones changes with age. A scheme illustrating the sequential development of competence in regulating the level of an enzyme is presented. 2. Actinomycin inhibited the effects of glucagon and BcAMP on liver tyrosine aminotransferase and glucose 6-phosphatase in foetal rats. Growth hormone, insulin and hydrocortisone did not enhance the formation of these enzymes. 3. The time-course of accumulation of glucose 6-phosphatase in the kidney is different from that in the liver. Hormones that increase the accumulation in foetal liver do not do so in the kidney of the same foetus or in the livers of postnatal rats.
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PMID:The hormonal regulation of enzymes in penatal and postnatal rat liver. Effects of adenosine 3',5'-(cyclic)-monophosphate. 418 80

Tyrosine aminotransferase induction has been studied in hepatocytes from untreated, partially and fully glucocorticoid-induced rats: enzyme activities were initially 12.9 +/- 1.7 (n = 16), 41.4 +/- 3.2 (n = 6) and 117.9 +/- 10.5 (n = 7) munits/mg protein, respectively. Untreated or fully induced hepatocytes maintain initial levels, whereas partially induced hepatocytes increase their tyrosine aminotransferase activity even in the presence of actinomycin D. Fully induced hepatocytes possess a normal protein synthetizing machinery and the mechanisms to degrade selectively tyrosine aminotransferase. The effect of progesterone treatment is consistent with these cells retaining a high dexamethasone level. Glucagon induces tyrosine aminotransferase via its second messenger, cyclic AMP. This induction decreases dramatically with in vivo glucocorticoid treatment. Time courses and effects of inhibitors are consistent with these in vivo and in vitro treatments being alternative methods of inducing tyrosine aminotransferase by the same basic pretranslational step.
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PMID:The regulation of hepatic tyrosine aminotransferase. 611 30

Hepatocytes from neo- and postnatal rat liver were isolated, purified from non-hepatocytes (erythropoietic cells), and cultured in sufficient quantity to investigate enzyme inducibility. Tyrosine aminotransferase (TAT) in neo- and postnatal hepatocytes was induced by maximally responsive doses of glucagon, dexamethasone, DB-cAMP, theophylline, and combinations thereof. In cultures from newborn parenchymal cells TAT enzyme-specific activity showed only a moderate inducibility; however, responsiveness to the combination was fully developed 10 days after birth and did not differ from values found in adult liver cells. The results also show the existence of the "permissive" effect of glucocorticoid during postnatal age, and indicate that the development of a possibly involved receptor complex for the induction of TAT is largely completed 5-10 days after birth.
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PMID:The inducibility of tyrosine aminotransferase in monolayer cultures of hepatocytes from neonatal rats. 613 Oct 69

The levels of the five enzymes of the urea cycle were measured in normal 5-week-old rats, in a transplantable hepatoma, and in the livers of tumor-bearing rats (host livers). The levels of all five enzymes were much lower in the hepatoma, although there was no exact correlation of the decrease in levels. In host livers, the levels were higher than in the tumors, but lower than in normal liver. The levels of all five urea cycle enzymes were positively correlated with dietary protein content in normal livers, in hepatomas, and in host livers. In fact, the hepatomas showed the greatest changes in response to diet. On all diets, the levels in host liver remained below those in normal liver, indicating that the decreased level was probably not due to preferential utilization of nutrients by the tumor. The levels of urea cycle enzymes in normal liver were not altered by a single injection of glucocorticoid, glucagon, or dibutyryl cyclic adenosine 3':5'-monophosphate. By contrast, in hepatoma, the levels were usually significantly elevated by the same treatment. In addition, the levels in host livers were always significantly elevated and were usually above those in normal animals, whether the latter were hormone treated or not. Injection of plasma from tumor-bearing rats into normal animals produced a decrease in the levels of all five enzymes; if glucagon was injected together with the plasma, large increases in levels were observed. This result supports the concept of a humoral factor produced by the tumor which affects the levels and the inducibility of urea cycle enzymes in host livers. Autopsied human primary hepatomas also showed levels of urea cycle enzymes below those in normal livers with host livers having intermediate values. A cell line derived from a human hepatoma showed induction of arginase by glucocorticoid in culture; in this, it resembled a cell line of the rat hepatoma. Tyrosine aminotransferase in human hepatoma cells was not induced by glucocorticoid; in this, it differed from the rat hepatoma cells where induction of this enzyme was observed.
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PMID:Regulation of urea cycle enzymes in transplantable hepatomas and in the livers of tumor-bearing rats and humans. 626 64

Tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) gene activity is stimulated by glucocorticoids and glucagon and is repressed by insulin. Expression and responsiveness to the different signal transduction pathways are restricted to the liver, in which the gene is activated shortly after birth. Here we provide a model for the basis of this tissue specificity of the hormonal control. In the two enhancers mediating hormone induction of TAT gene activity we find the hormone response elements in combination with binding sites for constitutive liver-enriched transcription factors: proteins of the hepatocyte nuclear factor 3 family bind in the vicinity of the glucocorticoid response element located 2.5 kb upstream of the transcription start site, while hepatocyte nuclear factor 4 interacts with an essential element in the cAMP-responsive enhancer at -3.6 kb. By juxtaposing the liver-specific element and the target sequence of the signal transduction pathway the regulatory properties of either enhancer can be reconstituted. Thus, the interdependence of the respective enhancer motifs restricts the hormonal activation of the TAT gene to the liver. The coincidence of the onset of TAT gene expression around birth with the perinatal changes in the concentrations of glucocorticoids, glucagon, and insulin suggests cooperation of signal transduction pathways and cell type-specific transcription factors in the developmental activation of the TAT gene.
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PMID:Activation of the tyrosine aminotransferase gene is dependent on synergy between liver-specific and hormone-responsive elements. 810 67

Tyrosine aminotransferase gene expression is confined to parenchymal cells of the liver, is inducible by glucocorticoids and glucagon, and is repressed by insulin. Three enhancers control this tissue-specific and hormone-dependent activity, one of which, located at -11 kb, is implicated in establishing an active expression domain. We have studied in detail this important regulatory element and have identified a 221-bp fragment containing critical enhancer sequences which stimulated the heterologous thymidine kinase promoter more than 100-fold in hepatoma cells. Within this region, we have characterized two essential liver-specific enhancer domains, one of which was bound by proteins of the hepatocyte nuclear factor 3 (HNF3) family. Analyses with the dedifferentiated hepatoma cell line HTC suggested that HNF3 alpha and/or -gamma, but not HNF3 beta, are involved in activating the tyrosine aminotransferase gene via the -11-kb enhancer. Genomic footprinting and in vitro protein-DNA binding studies documented cell-type-specific binding of ubiquitous factors to the second essential enhancer domain, which by itself stimulated the thymidine kinase promoter preferentially in hepatoma cells. These results will allow further characterization of the role of these enhancer sequences in developmental activation of the tyrosine aminotransferase gene.
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PMID:The distal enhancer implicated in the developmental regulation of the tyrosine aminotransferase gene is bound by liver-specific and ubiquitous factors. 810 32

Tyrosine aminotransferase (TyrAT) is one of several gluconeogenic enzymes which appear postnatally in humans and rodents in response to increased glucocorticoid and glucagon levels and decreased insulin. Primary cultured fetal rat hepatocytes older than day 15 of gestation (>E15) transcribe the TyrAT gene in response to the synergistic effect of dexamethasone and N6,2'-O-dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP), whereas less mature hepatocytes (<E15) do not [Shelly, L. L. & Yeoh, G. C. T. (1991) Eur. J. Biochem. 199, 475-481]. Therefore, we consider >E15 hepatocytes, and not <E15 hepatocytes, to be determined. This study reports that 11.1 kb of sequences upstream of the TyrAT transcription start site, which include a cAMP-responsive element (CRE) and a glucocorticoid-responsive element (GRE), are required for correct developmental regulation of gene expression in determined fetal hepatocytes. In contrast, the TyrAT CRE alone does not have this capability. Dexamethasone augments basal and Bt2cAMP-stimulated activity of the TyrAT CRE alone, suggesting that synergism may be due to interaction between the glucocorticoid and cAMP-signaling pathways. However, Bt2cAMP does not further increase dexamethasone-induced activity of the 11.1 kb 5' sequences when the TyrAT CRE is removed, thus excluding interaction of Bt2cAMP with the glucocorticoid pathway. Finally, insulin inhibition of dexamethasone-induced gene transcription is shown to be conferred by TyrAT 5' sequences. This study shows that cellular components, other than those which mediate hormonal regulation of genes, are required for determination of hepatocytes with respect to TyrAT. Since this phenomenon is observed with transient transfections, it is unlikely to involve higher-order chromatin structure.
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PMID:5' sequences direct developmental expression and hormone responsiveness of tyrosine aminotransferase in primary cultures of fetal rat hepatocytes. 939 13


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