Kastner A, Hirsch E C, Agid Y, Javoy-Agid F
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Brain Res. 1993 Mar 26;606(2):341-5. doi: 10.1016/0006-8993(93)91005-d.
To analyze the roles of transcriptional and post-transcriptional regulatory mechanisms of tyrosine hydroxylase (TH) gene expression during dopaminergic denervation in Parkinson's disease (PD), the cellular content of TH messenger RNA (mRNA) and TH protein in the substantia nigra were compared in control subjects and patients with PD. The average amounts of TH mRNA as well as those of TH protein per neuron were variable among controls but correlated to each other. In PD patients, both TH mRNA and TH protein content in nigral neurons were reduced relative to controls, however, the ratio between TH protein and TH mRNA levels was unaffected. The data suggest that, in PD: (1) TH protein content is decreased in the surviving nigral dopaminergic neurons, most likely as a result of a lowered TH mRNA cellular content. Thus the surviving neurons at end stages of the disease may be in a premorbid state. (2) The TH mRNA translation rate is not modified to compensate for dopamine deficiency.
为分析帕金森病（PD）中多巴胺能去神经支配期间酪氨酸羟化酶（TH）基因表达的转录和转录后调控机制的作用，我们比较了对照组和PD患者黑质中TH信使核糖核酸（mRNA）的细胞含量以及TH蛋白含量。对照组中每个神经元的TH mRNA平均含量以及TH蛋白平均含量各不相同，但二者相互关联。在PD患者中，黑质神经元中的TH mRNA和TH蛋白含量相对于对照组均降低，然而，TH蛋白水平与TH mRNA水平之间的比率未受影响。数据表明，在PD中：（1）存活的黑质多巴胺能神经元中TH蛋白含量降低，很可能是TH mRNA细胞含量降低的结果。因此，疾病终末期存活的神经元可能处于病前状态。（2）TH mRNA翻译率未发生改变以补偿多巴胺缺乏。
