Positive and negative cAMP-mediated control of tyrosine aminotransferase synthesis in Reuber H35 hepatoma cells.
Induction of L-tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5) by N6,O2'-dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP) in Reuber H35 hepatoma cells reaches a maximum value between 3-5 h after addition of Bt2cAMP and subsequently decreases in the continuous presence of Bt2cAMP. We have investigated the kinetics of the increase, i.e. induction, and the decrease, i.e. the repressed state, of the tyrosine-aminotransferase-synthesizing system under these conditions. Our experimental results are as follows. 1. The repressed state of the tyrosine-aminotransferase-synthesizing system is not caused by a decrease in the intracellular cAMP concentration. 2. The repressed state is inhibited by actinomycin D (while induction is not inhibited). 3. During the repressed state no effect of dexamethasone on tyrosine aminotransferase synthesis is found, while during induction Bt2cAMP and dexamethasone act synergistically. 4. Longer starvation of the cells in serum-free medium has no influence on the kinetics of the induction/repressed state curve. From these results we have concluded that the mechanism of the transition to the repressed state of the tyrosine-aminotransferase-synthesizing system is essentially different from the mechanism of deinduction which occurs after removal of the inducer. Moreover, the repressed state of the system is a phenomenon which is induced by Bt2cAMP separately from induction at a different level of protein synthesis.
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D007106:Immune Sera; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D007106:Immune Sera; D000242:Cyclic AMP; D014444:Tyrosine Transaminase