cAMP stimulates transcription of the gene for cytosolic phosphoenolpyruvate carboxykinase in rat liver nuclei.

Abstract

The effects of starvation, glucose refeeding, dibutyryl cAMP, and dexamethasone on expression of the gene for phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32] from rat liver cytosol was studied by using a cloned c[complementary]DNA probe. The rate of transcription of the gene for phosphoenolpyruvate carboxykinase in hepatic nuclei isolated from starved rats decreased rapidly after refeeding with glucose. Administration of dibutyryl cAMP to glucose-refed animals increased the rate of phosphoenolpyruvate carboxykinase gene transcription 7-fold within 20 min. Phosphoenolpyruvate carboxykinase mRNA in the cytosol is 2.8 kilobases long whereas liver nuclei contain 4 precursor RNA species that are up to 6.5 kilobases long. Feeding glucose to starved rats rapidly decreased the sequence abundance of enzyme mRNA in both nuclei and cytosol. The decrease in cytosolic phosphoenolpyruvate carboxykinase mRNA was preceded by a transient increase in enzyme mRNA over the 1st 20 min after glucose refeeding. Administration of dibutyryl cAMP to glucose-refed starved animals increased the concentration of the nuclear RNA precursors of phosphoenolpyruvate carboxykinase 5- to 8-fold within 30 min and induced the mRNA for the cytosolic enzyme over a period of 60 min. cAMP induces phosphoenolpyruvate carboxykinase mRNA by increasing the rate of gene transcription.