Adrenergic regulation of clock gene expression in mouse liver
Adrenergic regulation of clock gene expression in mouse liver
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DOI：
10.1073/pnas.0936797100
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发表时间：
2003-05-27
影响因子：
11.1
通讯作者：
Shibata, S
中科院分区：
文献类型：
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作者：
Terazono, H;Mutoh, T;Shibata, S
视交叉上核 (SCN) 中的主振荡器将昼夜节律信息传递到外围时钟系统，以调节基本生理功能。尽管在大鼠中观察到 SCN 和肝脏之间的多突触自主神经通路，但交感神经系统的激活是否会影响肝脏中的时钟基因表达尚不清楚。为了评估从 SCN 到肝组织的交感神经支配，我们研究了注射肾上腺素/去甲肾上腺素（肾上腺素/去甲肾上腺素）或交感神经刺激是否可以诱导小鼠肝脏中 mPer 基因的表达。急性施用肾上腺素或去甲肾上腺素会增加体内小鼠肝脏和体外肝切片中 mPer1 的表达，但不会增加 mPer2 的表达。电刺激交感神经或注射肾上腺素会导致携带 mPer1 启动子荧光素酶的转基因小鼠肝脏区域的生物发光升高。在明暗循环下，SCN 的破坏不仅使 mPer1、mPer2 和 mBmal1 基因的日节律变平，而且使肝脏中的去甲肾上腺素含量变平。每日固定时间注射肾上腺素，持续 6 天，第 7 天恢复了 SCN 损伤小鼠肝脏中 mPer2 和 mBmal1 基因表达的振荡。6-羟基多巴胺去交感神经使 mPer1 和 mPer2 基因表达的每日节律趋于平缓。因此，根据目前的结果，通过去甲肾上腺素和/或肾上腺素释放激活交感神经是控制外周时钟的一个因素。
A main oscillator in the suprachiasmatic nucleus (SCN) conveys circadian information to the peripheral clock systems for the regulation of fundamental physiological functions. Although polysynaptic autonomic neural pathways between the SCN and the liver were observed in rats, whether activation of the sympathetic nervous system entrains clock gene expression in the liver has yet to be understood. To assess sympathetic innervation from the SCN to liver tissue, we investigated whether injection of adrenaline/noradrenaline (epinephrine/norepinephrine) or sympathetic nerve stimulation could induce mPer gene expression in mouse liver. Acute administration of adrenaline or noradrenaline increased mPer1 but not mPer2 expression in the liver of mice in vivo and in hepatic slices in vitro. Electrical stimulation of the sympathetic nerves or adrenaline injection caused an elevation of bioluminescence in the liver area of transgenic mice carrying mPer1 promoter-luciferase. Under a light-dark cycle, destruction of the SCN flattened the daily rhythms of not only mPer1, mPer2, and mBmal1 genes but also noradrenaline content in the liver. Daily injection of adrenaline, administered at a fixed time for 6 days, recovered oscillations of mPer2 and mBmal1 gene expression in the liver of mice with SCN lesion on day 7. Sympathetic nerve denervation by 6-hydroxydopamine flattened the daily rhythm of mPer1 and mPer2 gene expression. Thus, on the basis of the present results, activation of the sympathetic nerves through noradrenaline and/or adrenaline release was a factor controlling the peripheral clock.