Factors regulating alphal (I) collagen mRNA turnover

为了了解大鼠灌胃50%四氯化碳（剂量为2ml /kg）的短期效果，在最初三天内检测了肝脏mRNA的周转。Northern分析表明，正常肝脏中ⅰ型胶原α链mRNA在给药72h后升高约30倍。这一增长幅度远远高于此前的报道。与正常大鼠相比，这种mRNA的降解率似乎没有改变，相反，据估计，这种蛋白质的基因转录活性是正常大鼠的三倍。与这种mRNA不同，Northern分析还表明，血清白蛋白mRNA在检查的时间过程的初始阶段减少。血清白蛋白mRNA在正常肝脏中翻转，半衰期为60h，但在CCl_4作用后，其半衰期为4h左右。在这一初始阶段，白蛋白基因转录同时降低到正常活性的10%以下，这种抑制状态持续48小时以上。由于这两个原因，在肝脏中，白蛋白mRNA首先下降。然而，这种mRNA的快速降解达到了明显的停止，随后是白蛋白mRNA不再降解的阶段，因此在接下来的48小时内，其水平是正常大鼠肝脏的一半。虽然I型胶原α链基因的转录激活是其mRNA水平升高的原因，但转录抑制和mRNA降解的刺激都是白蛋白mRNA显著降低的原因。甘油醛-3-磷酸脱氢酶mRNA水平在整个检查过程中似乎是稳定的。结果表明，CCl_4对大鼠肝脏的毒性作用通过不同机制影响不同mRNA种类的转换。

To know a short-term effect of the intragastric administration of 50% carbon tetrachloride to the rat at a dosage of 2 ml/kg, hepatic mRNA turnover was examined during the initial three days. Northern analysis demonstrated that type I collagen alphal chain mRNA which was trace in the normal liver increased to about 30 times higher level 72h after the CCl_4 administration. The extent of the increase was much higher than those reported previously. By comparison with the normal rat, the degradation rate of this mRNA did not appear to be altered, and instead the gene for this protein was estimated to be three times more actively transcried.Unlike this mRNA,Northern analysis also demonstrated that serum albumin mRNA is reduced at the initial stage within a time course examined. Serum albumin mRNA which was turned over with a half-life of 60h in the normal liver decayd with a half-life of 4h until about 6h after the CCl_4 administration. At this initial stage, the albumin gene transcription was simultaneously lowered below 10% of the normal activity, and this suppressed condition was prolonged over 48h. Because of the two reasons, in liver, mRNA for albumin first decreased. The rapid degradation of this mRNA,however, reached the apparent cessation, followed by the phase at which there is no more degradation of albumin mRNA,consequently giving its level half as much as that in the normal rat liver for following 48h. While rranscription activation of the type I collagen alphal chain gene was shown to be responsible for the increase in its mRNA level, both the transcription suppression and the stimulation in mRNA degradation were causative of the marked reduction of albumin mRNA.Glyceraldehyde-3-phosphate dehydrogenase mRNA level appeared to be stationary throughout the couse examined. The results demonstrate that the toxic condition induced in liver of the rat exposed to orally administered CCl_4 affects turnover of different mRNA species through different mechanisms.