Horbach G J, van Asten J G, van Bezooijen C F
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Biochem Pharmacol. 1990 Aug 1;40(3):529-33. doi: 10.1016/0006-2952(90)90552-v.
To investigate the influence of age on the regulation of the cytochromes P450IIB1 and P450IIB2 the levels of the messenger RNAs for these two cytochromes were determined in liver cytoplasmic RNA of rats of various ages after maximal induction with either phenobarbital or isosafrole and in untreated rats. The levels of these mRNAs were determined by solution hybridization with a RNA-probe (riboprobe system) complementary to both mRNAs. This study showed a marked decrease in the maximal induction levels of these mRNAs between the ages of 12 and 36 months irrespective of the type of inducer used. To assess whether this age-related decrease could be found for both individual mRNAs also solution hybridization experiments were performed with deoxyoligonucleotide probes of a defined sequence. The data presented in this paper show that ageing influences the levels of both the cytochrome P450IIB1 and P450IIB2 mRNA in a similar way. After induction the amount of mRNA for P450IIB1 was in all age groups measured four- to five-fold higher than that of P450IIB2. These data indicate that previously observed age-related changes in the cytochrome P450 system could be related to a lower accumulation of its mRNAs.
为研究年龄对细胞色素P450IIB1和P450IIB2调节的影响，在用苯巴比妥或异黄樟素最大诱导后，测定了不同年龄大鼠肝细胞质RNA以及未处理大鼠中这两种细胞色素信使RNA的水平。这些信使RNA的水平通过与两种信使RNA互补的RNA探针（核糖探针系统）进行溶液杂交来测定。本研究表明，无论使用何种诱导剂，在12至36月龄之间，这些信使RNA的最大诱导水平均显著下降。为评估这种与年龄相关的下降是否也适用于单个信使RNA，还使用特定序列的脱氧寡核苷酸探针进行了溶液杂交实验。本文给出的数据表明，衰老对细胞色素P450IIB1和P450IIB2信使RNA水平的影响方式相似。诱导后，所有年龄组中P450IIB1信使RNA的量均比P450IIB2高4至5倍。这些数据表明，先前观察到的细胞色素P450系统中与年龄相关的变化可能与其信使RNA积累减少有关。
