Ackermann Katrin, Dehghani Faramarz, Bux Roman, Kauert Gerold, Stehle Jörg H
Institute of Anatomy III, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
J Pineal Res. 2007 Sep;43(2):185-94. doi: 10.1111/j.1600-079X.2007.00461.x.
Rhythm generation within the mammalian circadian system is achieved by clock genes and their protein products. As an integral part of this system, the pineal gland serves the need to tune the body to the temporal environment by the rhythmic synthesis and release of melatonin. A number of human disorders and syndromes are associated with alterations in circadian rhythms of clock genes and their protein products and/or a dysfunction in melatonin synthesis. In the human, little is known about the molecular signature of time management. Pineal tissue from regular autopsies was allocated to asserted time-of-death groups (dawn, day, dusk, night), and analyzed by RT-PCR, immunoblotting, immunohistochemistry, and confocal laser scanning microscopy for expression of clock genes. Despite the observed diurnal rhythms in activity of the arylalkylamine N-acetyltransferase and in melatonin content, mRNA levels for the clock genes Period1, Cryptochrome1, Clock, and Bmal1, and also amounts of corresponding clock gene proteins showed no differences between time- of-death groups. In contrast, a time-of-day-dependent nucleocytoplasmic shuttling of clock gene proteins was detected. These data confirm the minor importance of a transcriptional regulation for dynamics in the human pineal gland, and offer a novel twist in the molecular competence of clock gene proteins.
哺乳动物昼夜节律系统中的节律产生是由生物钟基因及其蛋白质产物实现的。作为该系统的一个组成部分，松果体通过褪黑素的节律性合成和释放来满足使身体适应时间环境的需求。许多人类疾病和综合征都与生物钟基因及其蛋白质产物的昼夜节律改变和/或褪黑素合成功能障碍有关。在人类中，关于时间管理的分子特征知之甚少。将常规尸检获得的松果体组织分配到确定的死亡时间组（黎明、白天、黄昏、夜晚），并通过逆转录聚合酶链反应（RT-PCR）、免疫印迹、免疫组织化学和共聚焦激光扫描显微镜分析生物钟基因的表达。尽管观察到芳基烷基胺N-乙酰基转移酶活性和褪黑素含量存在昼夜节律，但死亡时间组之间生物钟基因Period1、隐花色素1、Clock和Bmal1的mRNA水平以及相应生物钟基因蛋白质的量均无差异。相反，检测到生物钟基因蛋白质存在时间依赖性的核质穿梭。这些数据证实了转录调控对人类松果体动态变化的重要性较小，并为生物钟基因蛋白质的分子能力提供了新的视角。
