Sukhareva E V, Dygalo N N, Kalinina T S
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.
Novosibirsk State University, Novosibirsk, 630090, Russia.
Mol Biol (Mosk). 2016 Mar-Apr;50(2):266-71. doi: 10.7868/S0026898416020257.
The ratio of the expression levels of the immediate early genes c-jun and c-fos that encode components of the AP-1 transcription complex determines the direction of changes in the expression of genes controlled by the complex, including changes induced by glucocorticoids. The aim of the present work was to assess the levels of mRNA encoded by genes c-jun and c-fos and the ratio of expression levels of these genes in various regions of the neonatal rat brain after the administration of dexamethasone, a selective ligand of the glucocorticoid receptor. The level of mRNA encoded by the immediate early gene c-fos in the hippocampus and prefrontal cortex of 3-day-old rat pups was elevated at 30, 60, and 120 min after dexamethasone administration. The basal level of c-fos gene expression in the brainstem was higher than in the cortex and hippocampus, and administration of the hormone was followed by a reduction in the amount of transcript detectable in the brainstem after 2 h. As a result, the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats was doubled after dexamethasone administration. The dexamethasone-induced shift of the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats towards a predominance of c-jun reported for the first time in the present work may induce the expression of genes that contain AP-1 response elements in the promoters, since the glucocorticoid receptor can be involved in protein-protein interactions with the Jun/Jun homodimer of the AP-1 complex.
编码AP-1转录复合体组分的即早基因c-jun和c-fos的表达水平之比,决定了受该复合体调控的基因表达变化的方向,包括糖皮质激素诱导的变化。本研究的目的是评估在给予糖皮质激素受体的选择性配体地塞米松后,新生大鼠脑不同区域中c-jun和c-fos基因编码的mRNA水平以及这些基因的表达水平之比。在给予地塞米松后30、60和120分钟,3日龄幼鼠海马体和前额叶皮质中即早基因c-fos编码的mRNA水平升高。脑干中c-fos基因的基础表达水平高于皮质和海马体,给予激素后2小时,脑干中可检测到的转录本数量减少。结果,给予地塞米松后,新生大鼠脑干中c-jun与c-fos转录本水平之比增加了一倍。本研究首次报道,地塞米松诱导新生大鼠脑干中c-jun与c-fos转录本水平之比向c-jun占优势的方向转变,这可能会诱导启动子中含有AP-1反应元件的基因表达,因为糖皮质激素受体可能参与与AP-1复合体的Jun/Jun同二聚体的蛋白质-蛋白质相互作用。