Schwartz William J, Aronin Neil, Sassone-Corsi Paolo
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
Neurosci Lett. 2005 Sep 2;385(1):87-91. doi: 10.1016/j.neulet.2005.05.018.
Several genes expressed in the suprachiasmatic nucleus (SCN) are induced by light and are candidate links in the photic entrainment pathway of the SCN's circadian clock. Since the cAMP response element binding protein (CREB) and CRE-mediated gene transcription in the SCN appears to be crucial for light-induced phase shifts of circadian rhythmicity, we analyzed the immunohistochemical expression of proteins encoded by the cAMP response element modulator (CREM) gene, including a repressor isoform (inducible cAMP early repressor [ICER]). ICER-CREM immunoreactivity was detected in cells of the ventrolateral subdivision of the rat SCN after light administration during the subjective night in constant darkness; but only late after light onset (at 240 min), following earlier successive peaks of phosphorylated CREB protein (by 5 min), c-fos mRNA (by 40 min), per 1 mRNA (by 55 min), and c-Fos protein (by 60 min). In constant darkness, there was a modest but significant endogenous rhythm of ICER-CREM immunoreactivity, with a two-fold difference between high levels at circadian time (CT) 10 and low levels at CT 22. Our data raise the possibility that ICER-CREM might be involved in downregulating the SCN expression of immediate-early and "clock" genes after their induction by phase-shifting light pulses.
视交叉上核（SCN）中表达的几种基因受光诱导，是SCN昼夜节律生物钟光信号同步途径中的候选连接点。由于SCN中的环磷酸腺苷反应元件结合蛋白（CREB）和CRE介导的基因转录对于昼夜节律的光诱导相移似乎至关重要，我们分析了环磷酸腺苷反应元件调节剂（CREM）基因编码的蛋白质的免疫组化表达，包括一种阻遏异构体（诱导型环磷酸腺苷早期阻遏物[ICER]）。在持续黑暗环境下的主观夜间给予光照后，在大鼠SCN腹外侧亚区的细胞中检测到ICER-CREM免疫反应性；但仅在光照开始后较晚时间（240分钟时）出现，此前依次出现磷酸化CREB蛋白（5分钟时）、c-fos mRNA（40分钟时）、per 1 mRNA（55分钟时）和c-Fos蛋白（60分钟时）的峰值。在持续黑暗环境中，ICER-CREM免疫反应性存在适度但显著的内源性节律，在昼夜时间（CT）10时的高水平与CT 22时的低水平之间存在两倍差异。我们的数据提出了一种可能性，即ICER-CREM可能在相移光脉冲诱导即刻早期基因和“时钟”基因后，参与下调SCN中这些基因的表达。
