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首页> 外文期刊>The European Journal of Neuroscience >Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus.
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Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus.

机译:光不会降解小鼠视交叉上核中组成型表达的BMAL1蛋白。

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摘要

Biological rhythms in mammals are driven by a central circadian clock located in the suprachiasmatic nucleus (SCN). At the molecular level the biological clock is based on the rhythmic expression of clock genes. Two basic helix-loop-helix (bHLH)/PAS-containing transcription factors, CLOCK and BMAL1 (MOP3), provide the basic drive to the system by activating transcription of negative regulators through E box enhancer elements. A critical feature of circadian timing is the ability of the clockwork to be entrained to the environmental light/dark cycle. The light-resetting mechanism of the mammalian circadian clock is poorly understood. Light-induced phase shifts are correlated with the induction of the clock genes mPer1 and mPer2 and a subsequent increase in mPER1 protein levels. It has previously been suggested that rapid degradation of BMAL1 protein in the rat SCN is part of the resetting mechanism of the central pacemaker. Our study shows that BMAL1 and CLOCK proteins are continuously expressed at highlevels in the mouse SCN, supporting the hypothesis that rhythmic negative feedback plays the major role in rhythm generation in the mammalian pacemaker. Using both immunocytochemistry and immunoblot analysis, our studies demonstrate that BMAL1 protein in the mouse SCN is not affected by a phase-resetting light pulse. These results indicate that rapid degradation of BMAL1 protein is not a consistent feature of resetting mechanisms in rodents.
机译:哺乳动物的生物节律是由位于视交叉上核(SCN)的中央生物钟驱动的。在分子水平上,生物钟是基于钟基因的有节奏表达。包含两个基本螺旋-环-螺旋(bHLH)/ PAS的转录因子CLOCK和BMAL1(MOP3)通过激活E框增强子元件激活负调控因子的转录,为系统提供了基本驱动力。昼夜节律计时的一个关键特征是发条能够被带入环境明暗周期的能力。对哺乳动物生物钟的光复位机制了解甚少。光诱导的相移与时钟基因mPer1和mPer2的诱导以及随后mPER1蛋白水平的增加相关。先前已经提出,大鼠SCN中BMAL1蛋白的快速降解是中央起搏器复位机制的一部分。我们的研究表明,BMAL1和CLOCK蛋白在小鼠SCN中连续高水平表达,支持以下假设:节律性负反馈在哺乳动物起搏器的节律产生中起主要作用。使用免疫细胞化学和免疫印迹分析,我们的研究表明,小鼠SCN中的BMAL1蛋白不受相变光脉冲的影响。这些结果表明,BMAL1蛋白的快速降解不是啮齿动物中重置机制的一致特征。

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