Properties, entrainment, and physiological functions of mammalian peripheral oscillators
Properties, entrainment, and physiological functions of mammalian peripheral oscillators
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DOI：
10.1177/0748730406293889
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发表时间：
2006-12-01
影响因子：
3.5
通讯作者：
Schibler, Ueli
中科院分区：
文献类型：
--
作者：
Stratmann, Markus;Schibler, Ueli
在哺乳动物中，昼夜节律计时系统由以分层方式组织的多个振荡器组成。位于下丘脑视交叉上核的中枢起搏器被认为协调了周围无数的辅助时钟。这些外围振荡器是细胞自主的，自我维持的，对细胞分裂有弹性，并且对一般转录速率的大波动几乎不敏感。然而，它们可能在器官内不耦合，并且似乎需要从SCN发出的每日授时因子信号来确保组织内和组织之间的相位相干性。外周生物钟与多种生化途径有关，最近的研究结果将昼夜节律与代谢的几个方面紧密联系起来。因此，在各种代谢途径中进行限速步骤的许多关键酶的表达以昼夜节律的方式由核心时钟组件或时钟控制的转录因子调节。遗传功能丧失研究现已确立哺乳动物生物钟成分在能量稳态和异生物质解毒中的作用，后者表现为药物功效和毒性的日间依赖性调节。
In mammals, the circadian timing system is composed of multiple oscillators that are organized in a hierarchical manner. The central pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, is believed to orchestrate countless subsidiary clocks in the periphery. These peripheral oscillators are cell-autonomous, self-sustained, resilient to cell division, and virtually insensitive to large fluctuations in general transcription rates. However, they are probably not coupled within an organ, and daily zeitgeber signals emanating from the SCN appear to be required to ensure phase coherence within and between tissues. Peripheral clocks are implicated in a variety of biochemical pathways, and recent results tightly link circadian rhythms to several aspects of metabolism. Thus, the expression of many key enzymes conducting rate-limiting steps in various metabolic pathways is regulated in a circadian fashion by core clock components or clock-controlled transcription factors. Genetic loss-of-function studies have now established a role for mammalian circadian clock components in energy homeostasis and xenobiotic detoxification, and the latter manifests itself in the daytime-dependent modulation of drug efficacy and toxicity.