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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Adrenergic regulation of clock gene expression in mouse liver
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Adrenergic regulation of clock gene expression in mouse liver

机译:肾上腺素调节小鼠肝脏时钟基因表达

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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 adrenalineoradrenaline (epinephrineorepinephrine) 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. [References: 43]
机译:视交叉上核(SCN)中的主振荡器将昼夜节律信息传送到外围时钟系统,以调节基本的生理功能。尽管在大鼠中观察到了SCN与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在肝脏中携带Clock基因表达尚待了解。为了评估从SCN到肝脏组织的交感神经支配,我们调查了注射肾上腺素/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的mPer基因表达。急性给药肾上腺素或去甲肾上腺素可增加小鼠体内和体外肝切片中mPer1的表达,但不增加mPer2的表达。交感神经的电刺激或肾上腺素注射导致携带mPer1启动子-荧光素酶的转基因小鼠肝脏中生物发光的升高。在光暗周期下,SCN的破坏不仅使mPer1,mPer2和mBmal1基因的每日节律变平,而且肝脏中的去甲肾上腺素含量也变平。每天注射肾上腺素,固定时间连续6天,在第7天恢复了SCN病变小鼠肝脏中mPer2和mBmal1基因表达的振荡。6-羟基多巴胺引起的交感神经去神经使mPer1和mPer2基因的每日节律趋于平坦表达。因此,根据目前的结果,通过去甲肾上腺素和/或肾上腺素的释放激活交感神经是控制周围时钟的因素。 [参考:43]

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