Balsalobre A, Marcacci L, Schibler U
Département de Biologie Moléculaire, Sciences II, Université de Genève, Switzerland.
Curr Biol. 2000 Oct 19;10(20):1291-4. doi: 10.1016/s0960-9822(00)00758-2.
In mammals, all overt circadian rhythms are thought to be coordinated by a central pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN) [1]. The phase of this pacemaker is entrained by photic cues via the retino-hypothalamic tract. Circadian clocks probably rely on a feedback loop in the expression of certain clock genes (reviewed in [2,3]). Surprisingly, however, such molecular oscillators are not only operative in pacemaker cells, such as SCN neurons, but also in many peripheral tissues and even in cell lines kept in vitro [4-7]. For example, a serum shock can induce circadian gene expression in cultured Rat-1 fibroblasts [5]. This treatment also results in a rapid surge of expression of the clock genes Per1 and Per2, similar to that observed in the SCNs of animals receiving a light pulse [8-10]. Serum induction of Per1 and Per2 transcription does not require ongoing protein synthesis [5] and must therefore be accomplished by direct signaling pathways. Here, we show that cAMP, protein kinase C, glucocorticoid hormones and Ca2+ can all trigger a transient surge of Per1 transcription and elicit rhythmic gene expression in Rat-1 cells. We thus suspect that the SCN pacemaker may exploit multiple chemical cues to synchronize peripheral oscillators in vivo.
在哺乳动物中，所有明显的昼夜节律都被认为是由位于下丘脑视交叉上核（SCN）的中央起搏器协调的[1]。该起搏器的相位通过视网膜下丘脑束受光信号的调节。昼夜节律钟可能依赖于某些时钟基因表达中的反馈回路（见[2,3]中的综述）。然而，令人惊讶的是，这种分子振荡器不仅在起搏器细胞（如SCN神经元）中起作用，而且在许多外周组织甚至体外培养的细胞系中也起作用[4-7]。例如，血清冲击可诱导培养的大鼠-1成纤维细胞中的昼夜节律基因表达[5]。这种处理还会导致时钟基因Per1和Per2的表达迅速激增，类似于在接受光脉冲的动物的SCN中观察到的情况[8-10]。血清诱导Per1和Per2转录不需要持续的蛋白质合成[5]，因此必须通过直接信号通路来完成。在这里，我们表明cAMP、蛋白激酶C、糖皮质激素和Ca2+都可以触发Per1转录的短暂激增，并在大鼠-1细胞中引发节律性基因表达。因此，我们怀疑SCN起搏器可能利用多种化学信号来使体内外周振荡器同步。
