Yamamoto Takuro, Nakahata Yasukazu, Tanaka Masami, Yoshida Mayumi, Soma Haruhiko, Shinohara Kazuyuki, Yasuda Akio, Mamine Takayoshi, Takumi Toru
Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
J Biol Chem. 2005 Dec 23;280(51):42036-43. doi: 10.1074/jbc.M509600200. Epub 2005 Oct 24.
In mammals, the circadian and stress systems (both centers of which are located in the hypothalamus) are involved in adaptation to predictable and unpredictable environmental stimuli, respectively. Although the interaction and relationship between these two systems are intriguing and have been studied in different ways since the "pre-clock gene" era, the molecular interaction between them remains largely unknown. Here, we show by systematic molecular biological analysis that acute physical stress elevated only Period1 (Per1) mRNA expression in mouse peripheral organs. Although behavioral rhythms in vivo and peripheral molecular clocks are rather stable against acute restraint stress, the results of a series of promoter analyses, including chromatin immunoprecipitation assays, indicate that a glucocorticoid-responsive element in the Per1 promoter is indispensable for induction of this mRNA both in vitro and in vivo. These results suggest that Per1 can be a potential stress marker and that a third pathway of Per1 transcriptional control may exist in addition to the clock-regulated CLOCK-BMAL1/E-box and light-responsive cAMP-responsive element-binding protein/cAMP-responsive element pathways.
在哺乳动物中，昼夜节律系统和应激系统（两者的中枢均位于下丘脑）分别参与对可预测和不可预测环境刺激的适应。尽管自“前生物钟基因”时代以来，这两个系统之间的相互作用和关系就很有趣且已通过不同方式进行了研究，但它们之间的分子相互作用在很大程度上仍不清楚。在此，我们通过系统的分子生物学分析表明，急性身体应激仅提高了小鼠外周器官中Period1（Per1）mRNA的表达。尽管体内行为节律和外周分子时钟对急性束缚应激相当稳定，但一系列启动子分析（包括染色质免疫沉淀试验）的结果表明，Per1启动子中的糖皮质激素反应元件对于该mRNA在体外和体内的诱导都是必不可少的。这些结果表明，Per1可能是一种潜在的应激标志物，并且除了时钟调节的CLOCK-BMAL1/E-box和光反应性环磷酸腺苷反应元件结合蛋白/环磷酸腺苷反应元件途径外，可能还存在Per1转录控制的第三条途径。
