Comparative functional genomics of adaptation to muscular disuse in hibernating mammals.

Comparative functional genomics of adaptation to muscular disuse in hibernating mammals.
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DOI:
10.1111/mec.12963
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发表时间:
2014-11
期刊:
影响因子:
4.9
通讯作者:
Barnes BM
Barnes BM
中科院分区:
生物学1区
文献类型:
--
作者:
Fedorov VB;Goropashnaya AV;Stewart NC;Tøien Ø;Chang C;Wang H;Yan J;Showe LC;Showe MK;Barnes BM

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冬眠是一种节能适应,涉及对体力活动的深度抑制,在季节性很强的环境中,冬眠可以持续 6-8 个月。虽然不动和废用会导致大多数哺乳动物物种的肌肉损失,但相比之下,冬眠的熊和地松鼠在冬季长期不活动的情况下表现出有限的肌肉萎缩,这表明冬眠的哺乳动物具有防止废用性肌肉萎缩的适应性机制。为了确定防止肌肉损失的分子机制背后的常见转录程序,我们使用定制的 9,600 探针 cDNA 微阵列对后肢肌肉进行了大规模基因表达筛选,比较冬眠和夏季活跃的黑熊和北极地松鼠。分子途径分析显示,在冬眠期间,两个物种的肌肉中参与蛋白质生物合成和核糖体生物发生的所有阶段的过度表达基因的比例升高,这表明在不同的冬眠状态下诱导翻译。蛋白质生物合成的诱导可能有助于通过长时间的冬眠不动来减轻废用性肌肉萎缩。蛋白质分解代谢途径基因缺乏方向性变化并不支持代谢抑制对于冬季保持肌肉质量的重要性。在这两个物种中检测到的参与氧化还原和葡萄糖代谢的多个基因的协调减少与冬眠不活动期间骨骼肌的代谢抑制和较低的能量需求是一致的。
Hibernation is an energy saving adaptation that involves a profound suppression of physical activity that can continue for 6-8 months in highly seasonal environments. While immobility and disuse generate muscle loss in most mammalian species, in contrast, hibernating bears and ground squirrels demonstrate limited muscle atrophy over the prolonged periods of physical inactivity during winter suggesting that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional programs that underlie molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screen in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels using custom 9,600 probe cDNA microarrays. A molecular pathway analysis showed an elevated proportion of over-expressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during torpor of hibernation that suggests induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through the prolonged periods of immobility of hibernation. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiple genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation.
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