Inhibition of tyrosine aminotransferase gene expression by retinoic acid. 1992

C J Pan, and L L Shelly, and D S Rabin, and J Y Chou
Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

Regulation of tyrosine aminotransferase (TAT) gene expression was examined in RALA255-10G, a simian virus-40 tsA mutant-immortalized adult rat hepatocyte line. At the nonpermissive temperature (40 C), these hepatocytes exhibited a differentiated phenotype and actively expressed the TAT gene, but only in the presence of dexamethasone (DEX). The glucocorticoid-mediated TAT expression was inhibited by cycloheximide, a protein synthesis inhibitor, and by RU486, a glucocorticoid antagonist, suggesting that glucocorticoid induction requires protein synthesis and may be mediated through hormone receptors. (Bu)2cAMP (Bt2cAMP) or retinoic acid, individually or in combination, failed to increase TAT mRNA levels. However, Bt2cAMP greatly potentiated the induction by DEX, whereas retinoic acid inhibited the induction by DEX or DEX/Bt2cAMP. Nuclear run-on assays demonstrated that the induction of TAT expression by DEX or DEX/Bt2cAMP in RALA255-10G cells is regulated primarily at the transcriptional level. In contrast, retinoic acid antagonized the DEX- or DEX/Bt2cAMP-mediated induction without affecting the rate of TAT gene transcription. Instead, retinoic acid destabilized TAT mRNA. The half-life values of TAT mRNA in DEX/Bt2cAMP- and DEX/Bt2cAMP/retinoic acid-treated cells were approximately 235-270 min and 90-100 min, respectively. Our results indicate that inhibition of TAT expression by retinoic acid was regulated primarily at the posttranscriptional level.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011965 Receptors, Glucocorticoid Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example. Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D003513 Cycloheximide Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. Actidione,Cicloheximide
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.

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