Factors regulating alphal (I) collagen mRNA turnover

调节 alpha (I) 胶原蛋白 mRNA 更新的因素

• 批准号: 06807010
• 负责人: HIRAGA Koichi
• 金额: $ 1.34万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807010/
• 关键词: alphal (I) collagen mRNA; Fat-storing cell; Albumin mRNA; Toxic hepatitis; I型コラゲンα1鎖

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.

为了了解以2 ml/kg剂量向大鼠胃内给予50%四氯化碳的短期效应，在最初三天内检查了肝脏mRNA的更新。北方分析表明，正常肝组织中微量的I型胶原mRNA在CCl_4处理后72小时即明显增加，约为对照组的30倍。增加的幅度比以前报告的要高得多。与正常大鼠相比，这种mRNA的降解速率似乎没有改变，相反，这种蛋白质的基因被估计为三倍更活跃地转录。与这种mRNA不同，北方分析也表明，血清白蛋白mRNA在检测的时间过程中的初始阶段减少。正常肝组织中半衰期为60小时的血清白蛋白mRNA在CCl_4处理后约6小时开始衰减，半衰期为4小时。在此初始阶段，白蛋白基因转录同时降低到正常活性的10%以下，并且这种抑制状态延长超过48小时。由于这两个原因，在肝脏中，白蛋白的mRNA首先下降。然而，这种mRNA的快速降解达到明显的停止，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，其水平为正常大鼠肝脏中的一半。Ⅰ型胶原蛋白链基因的转录激活导致其mRNA水平的升高，而白蛋白mRNA的转录抑制和mRNA降解的刺激则导致其mRNA水平的显著降低，甘油醛-3-磷酸脱氢酶mRNA水平在整个检测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的机制影响不同种类mRNA的周转。

项目成果

森ヶ崎 進: "四塩化炭素投与ラット肝におけるmRNAの代謝回転" 生化学. 67. 914- (1995)

Susumu Morigasaki：“四氯化碳处理的大鼠肝脏中的 mRNA 转换”生物化学 67. 914- (1995)。

Susumu Morigasaki: "Hepatic mRNA turnover in the rat following intragastric administration of carbon tetrachloride" Seikagaku. 677. 914 (1995)

Susumu Morigasaki：“大鼠胃内给予四氯化碳后肝脏 mRNA 的更新”Seikagaku。

森ヶ崎 進: "四塩化炭素投与ラット肝におけるI型コラゲンα1鎖mRNAレベルの調節" 生化学. 68. 66- (1996)

Susumu Morigasaki：“四氯化碳治疗大鼠肝脏中 I 型胶原 α1 链 mRNA 水平的调节”生物化学 68. 66- (1996)。

Susumu Morigasaki: "Regulation of hepatic alphal (I) collagen mRNA level in the rat that received carbon tetrachloride" Seikagaku. 68. 66 (1995)

Susumu Morigasaki：“接受四氯化碳的大鼠中肝脏 α1 (I) 胶原蛋白 mRNA 水平的调节”Seikagaku。