Noguchi T, Diesterhaft M, Granner D
J Biol Chem. 1982 Mar 10;257(5):2386-90.
A single injection of dibutyryl cyclic AMP (Bt2cAMP) into adrenalectomized rats results in rapid and proportionate increases in hepatic tyrosine aminotransferase catalytic activity and in the amount of functional mRNA coding for this enzyme. This effect is transient in that mRNATAT peaks at 0.065% of total poly(A)+RNA activity at 1 h and is back to the basal level of 0.012% in 2.5 h. Enzyme activity peaks at 2.5 h and is back to the basal level by 5 h. If Bt2cAMP is repeatedly injected (0, 1, 2.5, and 4 h), enzyme activity remains at maximal levels for 4 to 5 h, whereas changes in mRNATAT activity are identical with those observed in the single injected rats. The rate of tyrosine aminotransferase synthesis at 5.5 h in the multiply injected rats, a time when mRNATAT has already returned to the basal level, is 3 to 4 times greater than that in either control or singly injected rats at the same time (0.3% of total protein versus 0.07%) and is equivalent to the maximal rate seen 1 h after the initial injection of the cyclic nucleotide. Since the rate of synthesis is increased in proportion to the increase in enzyme catalytic activity, stabilization of the enzyme against degradation is excluded as an induction mechanism at this late time point. These responses are not due to differences in the metabolism of Bt2cAMP, and the effect depends on the presence of metabolically active derivatives of this nucleotide. It thus appears that Bt2cAMP induces the synthesis of tyrosine aminotransferase in rat liver in two distinct ways. One is pretranslational and involves a transient and rapid increase in mRNATAT activity. The second appears to involve a delayed but sustained increase in translation of a basal level of mRNATAT.
向肾上腺切除的大鼠单次注射二丁酰环磷酸腺苷（Bt2cAMP）会导致肝酪氨酸转氨酶催化活性以及编码该酶的功能性mRNA量迅速且成比例地增加。这种效应是短暂的，因为mRNATAT在1小时时达到总聚腺苷酸（poly(A)+）RNA活性的0.065%的峰值，并在2.5小时内回到0.012%的基础水平。酶活性在2.5小时时达到峰值，并在5小时时回到基础水平。如果重复注射Bt2cAMP（0小时、1小时、2.5小时和4小时），酶活性会在4至5小时内保持在最高水平，而mRNATAT活性的变化与单次注射大鼠中观察到的变化相同。在多次注射大鼠中，5.5小时时酪氨酸转氨酶的合成速率（此时mRNATAT已回到基础水平）比同一时间的对照或单次注射大鼠快3至4倍（占总蛋白的0.3%对0.07%），并且与最初注射环核苷酸1小时后观察到的最大速率相当。由于合成速率与酶催化活性的增加成比例增加，因此在这个较晚的时间点，酶免于降解的稳定化被排除作为诱导机制。这些反应不是由于Bt2cAMP代谢的差异引起的，并且这种效应取决于该核苷酸代谢活性衍生物的存在。因此，Bt2cAMP似乎以两种不同的方式诱导大鼠肝脏中酪氨酸转氨酶的合成。一种是翻译前的，涉及mRNATAT活性的短暂快速增加。第二种似乎涉及mRNATAT基础水平翻译的延迟但持续的增加。
