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蛰伏对西伯利亚仓鼠(黑线毛足鼠)生物钟相关基因心脏表达及蛋白质周转的影响。

Influence of torpor on cardiac expression of genes involved in the circadian clock and protein turnover in the Siberian hamster (Phodopus sungorus).

作者信息

Crawford Fiona I J, Hodgkinson Cassandra L, Ivanova Elena, Logunova Larisa B, Evans Gary J, Steinlechner Stephan, Loudon Andrew S I

机构信息

Faculty of Life Sciences, University of Manchester, Manchester, UK.

出版信息

Physiol Genomics. 2007 Nov 14;31(3):521-30. doi: 10.1152/physiolgenomics.00131.2007. Epub 2007 Sep 11.

Abstract

The Siberian hamster exhibits the key winter adaptive strategy of daily torpor, during which metabolism and heart rate are slowed for a few hours and body temperature declines by up to 20 degrees C, allowing substantial energetic savings. Previous studies of hibernators in which temperature drops by >30 degrees C for many days to weeks have revealed decreased transcription and translation during hypometabolism and identified several key physiological pathways involved. Here we used a cDNA microarray to define cardiac transcript changes over the course of a daily torpor bout and return to normothermia, and we show that, in common with hibernators, a relatively small proportion of the transcriptome (<5%) exhibited altered expression over a torpor bout. Pathways exhibiting significantly altered gene expression included transcriptional regulation, RNA stability and translational control, globin regulation, and cardiomyocyte function. Remarkably, gene representatives of the entire ubiquitylation pathway were significantly altered over the torpor bout, implying a key role for cardiac protein turnover and translation during a low-temperature torpor bout. The circadian clock maintained rhythmic transcription during torpor. Quantitative PCR profiling of heart, liver, and lung and in situ hybridization studies of clock genes in the hypothalamic circadian clock in the suprachiasmatic nucleus revealed that many circadian regulated transcripts exhibited synchronous alteration in expression during arousal. Our data highlight the potential importance of genes involved in protein turnover as part of the adaptive strategy of low-temperature torpor in a seasonal mammal.

摘要

西伯利亚仓鼠展现出每日蛰伏这一关键的冬季适应性策略,在此期间,新陈代谢和心率会减缓数小时,体温下降可达20摄氏度,从而大幅节省能量。此前对体温在数天至数周内下降超过30摄氏度的冬眠动物的研究表明,低代谢期间转录和翻译减少,并确定了几条关键的生理途径。在此,我们使用cDNA微阵列来确定每日蛰伏期间及恢复正常体温过程中心脏转录本的变化,并且我们发现,与冬眠动物一样,转录组中相对较小的一部分(<5%)在一次蛰伏期间表达发生了改变。基因表达显著改变的途径包括转录调控、RNA稳定性和翻译控制、珠蛋白调控以及心肌细胞功能。值得注意的是,整个泛素化途径的基因代表在蛰伏期间均发生了显著改变,这意味着在低温蛰伏期间心脏蛋白质周转和翻译起着关键作用。生物钟在蛰伏期间维持节律性转录。对心脏、肝脏和肺进行定量PCR分析,以及对视交叉上核下丘脑生物钟中的生物钟基因进行原位杂交研究,结果显示许多受生物钟调控的转录本在苏醒期间表达呈现同步变化。我们的数据突出了参与蛋白质周转的基因作为季节性哺乳动物低温蛰伏适应性策略一部分的潜在重要性。

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