Albrecht J H, Muller-Eberhard U, Kren B T, Steer C J
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota 55415.
Arch Biochem Biophys. 1994 Oct;314(1):229-33. doi: 10.1006/abbi.1994.1434.
The hepatic response to systemic injury is characterized by alterations in the synthesis of plasma proteins, while acute injury to the liver can lead to rapid proliferation of hepatocytes. The hemopexin gene was found to be markedly induced in rat liver following both sham surgery (SS) and 70% partial hepatectomy (PH), models of systemic injury and hepatic proliferation, respectively. Transcriptional and post-transcriptional regulation of this gene was evaluated to examine the mechanisms of hemopexin mRNA expression in these models. Significant transcriptional activation was observed within 6 h of either surgery, with a more pronounced effect after PH. In both processes, transcription rates returned to baseline values by 24 h after surgery, although marked elevations in mRNA steady-state levels were noted for at least 72 h. At each time point, levels of hemopexin mRNA were more abundant following PH than after SS, in part due to greater transcriptional induction. In addition, posttranscriptional mechanisms appeared to contribute to the increased expression of hemopexin post-PH. The in vivo half-life of the 1.6-kb hemopexin transcript was determined to be considerably greater than 12 h in control, sham-operated, and PH animals. The exceptionally long mRNA half-life appears to be an important but complex factor in the kinetics of hemopexin gene regulation.
肝脏对全身损伤的反应特征在于血浆蛋白合成的改变，而肝脏的急性损伤可导致肝细胞快速增殖。分别作为全身损伤和肝脏增殖模型的假手术（SS）和70%部分肝切除术（PH）后，发现大鼠肝脏中的血红素结合蛋白基因被显著诱导。对该基因的转录和转录后调控进行评估，以研究这些模型中血红素结合蛋白mRNA表达的机制。在任一手术后6小时内均观察到显著的转录激活，PH后效应更明显。在这两个过程中，尽管在至少72小时内观察到mRNA稳态水平显著升高，但手术后24小时转录率恢复到基线值。在每个时间点，PH后血红素结合蛋白mRNA水平比SS后更丰富，部分原因是转录诱导更强。此外，转录后机制似乎有助于PH后血红素结合蛋白表达的增加。在对照、假手术和PH动物中，1.6 kb血红素结合蛋白转录本的体内半衰期被确定为远大于12小时。异常长的mRNA半衰期似乎是血红素结合蛋白基因调控动力学中的一个重要但复杂的因素。
