Evaluation of thyroid hormone effects on liver P450 reductase translation.
Evaluation of thyroid hormone effects on liver P450 reductase translation.
复制标题
评估甲状腺激素对肝脏 P450 还原酶翻译的影响。
DOI：
10.1016/s0003-9861(02)00417-4
复制
发表时间：
2003
影响因子：
3.9
通讯作者：
Waxman,DavidJ
中科院分区：
文献类型：
--
作者：
Apletalina,EkaterinaV;Li,HuanChen;Waxman,DavidJ
大鼠肝脏NADPH细胞色素P450氧化还原酶（P450R）的表达受甲状腺激素（T3）的正调节，在转录和转录后水平。在这里，我们研究T3诱导的甲亢对P450 R蛋白合成的调节的影响。T3处理成年雄性大鼠导致肝脏P450 R mRNA的强烈诱导（高达10倍），但P450 R蛋白和活性几乎没有变化。对这种差异的研究表明，T3处理并没有改变肝脏P450 R mRNA与多聚体的相关性，这表明P450 R mRNA和蛋白水平的不协调变化并不反映T3诱导的P450 R mRNA进入多聚体的募集减少。此外，P450 R mRNA的多核糖体大小分布分析没有显示任何T3依赖性的变化。当在体外翻译系统中测定时，T3诱导的和未诱导的P450 R mRNA以相似的效率翻译。此外，T3处理的大鼠肝细胞提取物没有选择性地抑制T3诱导的P450 R mRNA的体外翻译。因此，无论是在P450 R mRNA的结构变化，也没有反式作用结合蛋白在肝细胞质中被发现控制翻译的P450 R mRNA的T3处理。两者合计，这些数据表明，P450 R可能在甲状腺功能亢进大鼠肝脏中的蛋白质稳定性水平上受到部分调节。
The expression of NADPH cytochrome P450 oxidoreductase (P450R) in rat liver is positively regulated by thyroid hormone (T3), at both the transcriptional and post-transcriptional levels. Here we investigate the effects of T3-induced hyperthyroidism on the regulation of P450R protein synthesis. T3 treatment of adult male rats led to a strong induction (up to ∼10-fold) of liver P450R mRNA but little or no change in P450R protein and activity. Investigation of this discrepancy revealed that the association of hepatic P450R mRNA with polysomes was not altered by T3 treatment, suggesting that the discoordinate changes in P450R mRNA and protein levels do not reflect decreased recruitment of T3-induced P450R mRNA into polysomes. Moreover, polysome size distribution analysis of P450R mRNA did not show any T3-dependent changes. When assayed in an in vitro translation system, T3-induced and uninduced P450R mRNAs were translated with similar efficiencies. Moreover, liver cell extract from T3-treated rats did not selectively inhibit in vitro translation of T3-induced P450R mRNA. Thus, neither structural changes in P450R mRNA nor trans-acting binding proteins in liver cytosol were found to control translation of P450R mRNA in response to T3 treatment. Taken together, these data suggest that P450R may in part be regulated at the level of protein stability in hyperthyroid rat liver.