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The induction, desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP in rat hepatoma cells.
Biochem J. 1988 Apr 01; 251(1):261-7.BJ

Abstract

Addition of 1-3 mM-8-bromo-cyclic AMP to monolayer cultures of H-4 rat hepatoma cells resulted in a rapid but short-lived increase in tyrosine aminotransferase (EC 2.6.1.5) activity. The transient nature of this induction is due to desensitization to 8-bromo-cyclic AMP. Throughout this time course of induction and desensitization, removal of 8-bromo-cyclic AMP resulted in a rapid and significant decrease in tyrosine aminotransferase activity, a process referred to as 'de-induction' in this study. We showed that the changes in tyrosine aminotransferase activity in its induction, desensitization and de-induction by 8-bromo-cyclic AMP were directly attributable to changes in the synthesis rate of the protein, and the amount of translatable and hybridizable mRNA encoding for tyrosine aminotransferase (mRNATAT). We further showed that this desensitization was specific to cyclic AMP. First, only active analogues of cyclic AMP and agents which increased cellular concentrations of cyclic AMP elicited this desensitization. Second, the desensitized cells were refractory only to the effects of 8-bromo-cyclic AMP; dexamethasone and insulin induced the tyrosine aminotransferase activity in the 8-bromo-cyclic AMP-desensitized cells in a manner similar to that of the controls. Studies on the metabolism of 8-bromo-cyclic AMP suggest that neither its degradation nor the accumulation of its primary metabolite, 8-bromoadenosine, played a significant role in modulating the expression of tyrosine aminotransferase during the time course of action of 8-bromo-cyclic AMP. These results provide evidence for a specific pretranslational mode of action of cyclic AMP in the control of tyrosine aminotransferase expression in its desensitization and de-induction, in addition to the early phase of induction.

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Authors+Show Affiliations

Smith JD
Department of Pharmacology, Harvard Medical School, Boston, MA 02115.
Liu AY
No affiliation info available

MeSH

8-Bromo Cyclic Adenosine MonophosphateAnimalsCell LineDexamethasoneElectrophoresis, Polyacrylamide GelEnzyme InductionInsulinLiver Neoplasms, ExperimentalNucleic Acid HybridizationPhosphoenolpyruvate Carboxykinase (GTP)RNA, MessengerRatsTumor Cells, CulturedTyrosine Transaminase

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

2898939

Citation

Smith, J D., and A Y. Liu. "The Induction, Desensitization and De-induction of Tyrosine Aminotransferase By 8-bromo-cyclic AMP in Rat Hepatoma Cells." The Biochemical Journal, vol. 251, no. 1, 1988, pp. 261-7.
Smith JD, Liu AY. The induction, desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP in rat hepatoma cells. Biochem J. 1988;251(1):261-7.
Smith, J. D., & Liu, A. Y. (1988). The induction, desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP in rat hepatoma cells. The Biochemical Journal, 251(1), 261-7.
Smith JD, Liu AY. The Induction, Desensitization and De-induction of Tyrosine Aminotransferase By 8-bromo-cyclic AMP in Rat Hepatoma Cells. Biochem J. 1988 Apr 1;251(1):261-7. PubMed PMID: 2898939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The induction, desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP in rat hepatoma cells. AU - Smith,J D, AU - Liu,A Y, PY - 1988/4/1/pubmed PY - 1988/4/1/medline PY - 1988/4/1/entrez SP - 261 EP - 7 JF - The Biochemical journal JO - Biochem J VL - 251 IS - 1 N2 - Addition of 1-3 mM-8-bromo-cyclic AMP to monolayer cultures of H-4 rat hepatoma cells resulted in a rapid but short-lived increase in tyrosine aminotransferase (EC 2.6.1.5) activity. The transient nature of this induction is due to desensitization to 8-bromo-cyclic AMP. Throughout this time course of induction and desensitization, removal of 8-bromo-cyclic AMP resulted in a rapid and significant decrease in tyrosine aminotransferase activity, a process referred to as 'de-induction' in this study. We showed that the changes in tyrosine aminotransferase activity in its induction, desensitization and de-induction by 8-bromo-cyclic AMP were directly attributable to changes in the synthesis rate of the protein, and the amount of translatable and hybridizable mRNA encoding for tyrosine aminotransferase (mRNATAT). We further showed that this desensitization was specific to cyclic AMP. First, only active analogues of cyclic AMP and agents which increased cellular concentrations of cyclic AMP elicited this desensitization. Second, the desensitized cells were refractory only to the effects of 8-bromo-cyclic AMP; dexamethasone and insulin induced the tyrosine aminotransferase activity in the 8-bromo-cyclic AMP-desensitized cells in a manner similar to that of the controls. Studies on the metabolism of 8-bromo-cyclic AMP suggest that neither its degradation nor the accumulation of its primary metabolite, 8-bromoadenosine, played a significant role in modulating the expression of tyrosine aminotransferase during the time course of action of 8-bromo-cyclic AMP. These results provide evidence for a specific pretranslational mode of action of cyclic AMP in the control of tyrosine aminotransferase expression in its desensitization and de-induction, in addition to the early phase of induction. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/2898939/The_induction_desensitization_and_de_induction_of_tyrosine_aminotransferase_by_8_bromo_cyclic_AMP_in_rat_hepatoma_cells_ DB - PRIME DP - Unbound Medicine ER -
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