Multiple signaling pathways elicit circadian gene expression in cultured Rat-1 fibroblasts
Multiple signaling pathways elicit circadian gene expression in cultured Rat-1 fibroblasts
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DOI：
10.1016/s0960-9822(00)00758-2
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发表时间：
2000-10-19
期刊：
影响因子：
9.2
通讯作者：
Schibler, U
中科院分区：
文献类型：
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作者：
Balsalobre, A;Marcacci, L;Schibler, U
在哺乳动物中，所有明显的昼夜节律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]。这种起搏器的相位是通过视网膜-下丘脑束的光信号来引导的。生物钟可能依赖于某些DOCK基因表达的反馈环(在[2，3]中综述)，然而，令人惊讶的是，这种分子振荡器不仅在起搏细胞中起作用，如SCN神经元，而且在许多外周组织中，甚至在体外培养的细胞系中也是如此[4-7]，例如，血清休克可以诱导培养的大鼠成纤维细胞的昼夜基因表达[5]。这种治疗还导致时钟基因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[8-10]，血清诱导PERT和PER2转录不需要正在进行的蛋白质合成[5]，因此必须通过直接信号通路完成。在这里，我们发现cAMP、蛋白激酶C、糖皮质激素和钙离子都可以在大鼠-1细胞中触发PER1转录的瞬时激增，并诱导节律性基因表达。因此，我们怀疑SCN起搏器可能利用多种化学线索来同步体内的外周振荡器。
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 dock 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 Pert 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.