Baki L, Alexis M N
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Biochem J. 1996 Dec 15;320 ( Pt 3)(Pt 3):745-53. doi: 10.1042/bj3200745.
Following 70% hepatectomy, the induction of tyrosine amino-transferase mRNA by glucocorticoids was marginal at 1.5 h, significantly impaired between 3 and 8 h and, at 16 h post-hepatectomy, reached a value approx. 5-fold the basal level, similar to the level observed in quiescent liver. The fold induction of the mRNA was accounted for by a similar fold activation of transcription of the gene by glucocorticoids in regenerating but not in quiescent liver; in the latter, activation of transcription was marginal in spite of glucocorticoid-induced hypersensitivity to cleavage by DNase I at the glucocorticoid-dependent enhancer of the gene. The possibility that in quiescent liver glucocorticoids act at a transcriptional step beyond initiation, increasing the rate of elongation or overcoming a blockage in elongation, was excluded. However, a similar fold induction was determined for total and nuclear tyrosine aminotransferase mRNA in the presence of glucocorticoids, suggesting that in quiescent liver glucocorticoids promote efficient maturation of the tyrosine aminotransferase primary transcript. Thus a glucocorticoid-induced nuclear post-transcriptional up-regulation apparently compensates for impaired activation of transcription of the tyrosine aminotransferase gene by glucocorticoids in quiescent liver.
在进行70%肝切除术后，糖皮质激素诱导的酪氨酸氨基转移酶mRNA在术后1.5小时仅呈现微弱诱导，在3至8小时显著受损，而在肝切除术后16小时，其水平达到约基础水平的5倍，与静止肝脏中观察到的水平相似。mRNA的诱导倍数是由糖皮质激素在再生肝脏而非静止肝脏中对该基因转录的相似倍数激活所致；在静止肝脏中，尽管糖皮质激素诱导对基因糖皮质激素依赖性增强子处的DNA酶I切割超敏，但转录激活仍很微弱。静止肝脏中糖皮质激素在起始转录之后的步骤起作用、增加延伸速率或克服延伸阻滞的可能性被排除。然而，在存在糖皮质激素的情况下，总酪氨酸氨基转移酶mRNA和核酪氨酸氨基转移酶mRNA的诱导倍数相似，这表明在静止肝脏中糖皮质激素促进酪氨酸氨基转移酶初级转录本的有效成熟。因此，糖皮质激素诱导的核转录后上调显然弥补了静止肝脏中糖皮质激素对酪氨酸氨基转移酶基因转录激活受损的情况。
