Regulation of the synthesis of tyrosine aminotransferase: the relationship to mRNATAT

Granner, Daryl K.; Hargrove, James L.

doi:10.1007/978-1-4613-3879-6_7

Cited by 7 publications

(6 citation statements)

References 113 publications

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“…Therefore, CS are major regulators of this transcription. In addition, the TAT gene is also regulated by cAMP and insulin [53,54]. The TAT mRNA and activity followed a marked circadian variation which was postulated to be mediated by the circadian rhythm of CST [22].…”

Section: Discussionmentioning

confidence: 99%

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Hazra

Pyszczynski

DuBois

et al. 2007

J Pharmacokinet Pharmacodyn

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Receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase (TAT) were evaluated in normal rats. A group of normal male Wistar rats were injected with 50 mg/kg methylprednisolone (MPL) intramuscularly at the nadir of their plasma corticosterone (CST) rhythm (early light cycle) and sacrificed at various time points up to 96 h post-treatment. Blood and livers were collected to measure plasma MPL, CST, hepatic glucocorticoid receptor (GR) mRNA, cytosolic GR density, TAT mRNA, and TAT activity. The pharmacokinetics of MPL showed bi-exponential disposition with two first-order absorption components from the injection NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript site and bioavailability was 21%. Plasma CST was reduced after MPL dosing, but resumed its daily circadian pattern within 36 h. Cytosolic receptor density was significantly suppressed (90%) and returned to baseline by 72 h resuming its biphasic pattern. Hepatic GR mRNA follows a circadian pattern which was disrupted by MPL and did not return during the study. MPL caused significant down-regulation (50%) in GR mRNA which was followed by a delayed rebound phase (60-70 h). Hepatic TAT mRNA and activity showed up-regulation as a consequence of MPL, and returned to their circadian baseline within 72 and 24 h of treatment. A mechanistic receptor/genemediated pharmacokinetic/pharmacodynamic model was able to satisfactorily describe the complex interplay of exogenous and endogenous corticosteroid effects on hepatic GR mRNA, cytosolic free GR, TAT mRNA, and TAT activity in normal rats.

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Section: Discussionmentioning

confidence: 99%

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Hazra

Pyszczynski

DuBois

et al. 2007

J Pharmacokinet Pharmacodyn

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“…First of all, we have not studied specifically those genes known to have a strong dependence on specific hormones (e.g., gluconeogenic enzymes [12]). We noted earlier (4) and also found in the present experiments that transcription of plivS-1 (MUP) RNA was the most sensitive to disaggregation in our series of liver-specific genes.…”

Section: Discussionmentioning

confidence: 99%

Dependence of liver-specific transcription on tissue organization.

1985

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When the liver is disaggregated and hepatocytes are cultured as a cellular monolayer for 24 h, a sharp decline (80 to 99% decrease) in the transcription of most liver-specific mRNAs, but not common mRNAs, occurs (Clayton and Darnell, Mol. Cell. Biol. 2:1552-1561. A wide variety of culture conditions involving various hormones and substrates and cocultivation with other cells failed to sustain high rates of liver-specific mRNA synthesis in cultured hepatocytes, although they continued to synthesize common mRNAs at normal or elevated rates. In contrast, when slices of intact mouse liver tissue were placed in culture, the transcription of liver-specific genes was maintained at high levels (20 to 100% of normal liver). Furthermore, we found that cells in the liver could be disengaged and immediately reengaged in a tissue-like structure by perfusing the liver with EDTA followed by serum-containing culture medium. Slices of reengaged liver continued to transcribe tissue-specific mRNA sequences at significantly higher rates after 24 h in culture than did individual cells isolated by EDTA perfusion followed by culturing as a monolayer. Therefore we conclude that a mature tissue structure plays an important role in the maintenance of maximum tissue-specific transcription in liver cells.

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“…The TAT gene is expressed specifically in the parenchymal cells of the liver, where its transcription is stimulated by glucocorticoids and glucagon (for a review, see reference 19). Full glucocorticoid induction of the rat TAT gene is achieved through the cooperative interaction of two remote glucocorticoid-responsive units (GRUs) located at kb Ϫ2.5 (Ϫ2.5 GRU) and kb Ϫ5.5 (17,22), whereas the glucagon-cAMP response is mediated by a cAMP-responsive unit located at kb Ϫ3.6 (9).…”

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confidence: 99%

Glucocorticoids and Protein Kinase A Coordinately Modulate Transcription Factor Recruitment at a Glucocorticoid-Responsive Unit

Espinás

Roux

Pictet

et al. 1995

Molecular and Cellular Biology

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The rat tyrosine aminotransferase gene is a model system to study transcriptional regulation by glucocorticoid hormones. We analyzed transcription factor binding to the tyrosine aminotransferase gene glucocorticoid-responsive unit (GRU) at kb ؊2.5, using in vivo footprinting studies with both dimethyl sulfate and DNase I. At this GRU, glucocorticoid activation triggers a disruption of the nucleosomal structure. We show here that various regulatory pathways affect transcription factor binding to this GRU. The binding differs in two closely related glucocorticoid-responsive hepatoma cell lines. In line H4II, glucocorticoid induction promotes the recruitment of hepatocyte nuclear factor 3 (HNF3), presumably through the nucleosomal disruption. However, the footprint of the glucocorticoid receptor (GR) is not visible, even though a regular but transient interaction of the GR is necessary to maintain HNF3 binding. In contrast, in line FTO2B, HNF3 binds to the GRU in the absence of glucocorticoids and nucleosomal disruption, showing that a ''closed'' chromatin conformation does not repress the binding of certain transcription factors in a uniform manner. In FTO2B cells, the footprint of the GR is detectable, but this requires the activation of protein kinase A. In addition, protein kinase A stimulation also improves the recruitment of HNF3 independently of glucocorticoids and enhances the glucocorticoid response mediated by this GRU in an HNF3-dependent manner. In conclusion, the differences in the behavior of this regulatory sequence in the two cell lines show that various regulatory pathways are integrated at this GRU through modulation of interrelated events: transcription factor binding to DNA and nucleosomal disruption.

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Regulation of the synthesis of tyrosine aminotransferase: the relationship to mRNATAT

Cited by 7 publications

References 113 publications

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Dependence of liver-specific transcription on tissue organization.

Glucocorticoids and Protein Kinase A Coordinately Modulate Transcription Factor Recruitment at a Glucocorticoid-Responsive Unit

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