Kako K, Banasik M, Lee K, Ishida N
National Institute of Bioscience and Human Technology, Agency of Industrial Science and Technology, MITI, Tsukuba, Ibaraki, Japan.
Brain Res Mol Brain Res. 1997 Feb;44(1):39-45. doi: 10.1016/s0169-328x(96)00202-1.
Mammalian circadian rhythms are considered to be regulated by a clock pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The molecular mechanism of entrainment and oscillation of circadian rhythm are not well understood but photic induction of immediate-early gene (IEG) expression in the SCN is thought to play a role. Here we show that under 12 h light:12 h dark (LD) condition, the cAMP response element binding protein (CREB) binding to cAMP responsive promoter element (CRE) of NMDAR1/zeta1 promoter region in the SCN is higher during the light than the dark by electro-mobility shift assay (EMSA). When animals are placed in constant dark, CREB DNA binding activity in the SCN is low and does not vary with circadian time when compared with cortex nuclear extract as a control. Most significantly, photic induction of CREB binding activity in the SCN occurs at all circadian times tested, indicating that CREB DNA binding in the SCN is not gated by the endogenous clock. These results implicate the role of CREB in photic neuronal signaling in the SCN and suggest that CREB DNA binding activities may not be regulated by a circadian clock.
哺乳动物的昼夜节律被认为是由位于下丘脑视交叉上核（SCN）的生物钟起搏器调节的。昼夜节律的同步化和振荡的分子机制尚未完全了解，但SCN中即刻早期基因（IEG）表达的光诱导被认为发挥了作用。在这里，我们表明，在12小时光照：12小时黑暗（LD）条件下，通过电泳迁移率变动分析（EMSA），SCN中与NMDAR1/ζ1启动子区域的cAMP反应元件结合蛋白（CREB）结合到cAMP反应性启动子元件（CRE）上的情况在光照期间高于黑暗期间。当动物处于持续黑暗中时，与作为对照的皮质核提取物相比，SCN中的CREB DNA结合活性较低，并且不随昼夜时间变化。最显著的是，在所有测试的昼夜时间都出现了SCN中CREB结合活性的光诱导，这表明SCN中的CREB DNA结合不受内源性生物钟的控制。这些结果暗示了CREB在SCN光神经元信号传导中的作用，并表明CREB DNA结合活性可能不受昼夜节律钟的调节。
