Molecular Mechanism Underlying Muscle Mass Retention in Hibernating Bats: Role of Periodic Arousal

Molecular Mechanism Underlying Muscle Mass Retention in Hibernating Bats: Role of Periodic Arousal
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DOI:
10.1002/jcp.21952
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发表时间:
2010-02-01
影响因子:
5.6
通讯作者:
Choi, Inho
Choi, Inho
中科院分区:
生物学2区
文献类型:
--
作者:
Lee, Kisoo;So, Hyekyoung;Choi, Inho

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蝙蝠等冬眠动物在长时间的冬眠中只表现出轻微的肌肉萎缩。目前的研究旨在验证这一假设,即冬眠动物使用周期性的唤醒来增加蛋白质含量,以补偿废用期间持续的肌肉蛋白质水解。为了验证这一假设,我们调查了3个月的冬眠(HB)和7天的唤醒后的麻痹(TP),然后再唤醒(RA)的信号活动在胸肌的夏季活跃(SA)和休眠的白腹蝙蝠。蝙蝠没有失去肌肉质量相对于身体质量在HB或TP到RA期间。在觉醒后的前30分钟,肌电尖峰的峰值幅度和频率分别增加了3.1倍和1.4倍,表明颤抖期间大量的肌纤维募集和运动信号升高。全组织裂解物的免疫印迹分析揭示了几个主要结果:(1)对于3个月的HB,Akt I(p-Akt I)和p-mTOR的磷酸化水平与SA蝙蝠相比显著降低,但p-FoxO I水平保持不变;(2)对于TP至RA期间,p-Akt I和p-FoxO I变化很小,而p-mTOR显示双相振荡;(3)蛋白水解信号(即,atrogin-1、MuRF I、Skp 2和钙蛋白酶-1)在HB和TP至RA期间保持恒定。这些结果表明,麻痹蝙蝠肌肉对萎缩的抵抗特性可能主要通过相对恒定的蛋白水解结合振荡的合成代谢活性(例如,p-mTOR)对应于整个冬眠期间发生的觉醒频率。J.细胞。222:313- 319,2010。(C)2009 Wiley-Liss,Inc.
Hibernators like bats show only marginal muscle atrophy during prolonged hibernation. The current study was designed to test the hypothesis that hibernators use periodic arousal to increase protein anabolism that compensates for the continuous muscle proteolysis during disuse. To test this hypothesis, we investigated the effects of 3-month hibernation (HB) and 7-day post-arousal torpor (TP) followed by re-arousal (RA) on signaling activities in the pectoral muscles of summer-active (SA) and dormant Murina leucogaster bats. The bats did not lose muscle mass relative to body mass during the HB or TP-to-RA period. For the first 30-min following arousal, the peak amplitude and frequency of electromyographic spikes increased 3.1- and 1.4-fold, respectively, indicating massive myofiber recruitment and elevated motor signaling during shivering. Immunoblot analyses of whole-tissue lysates revealed several principal outcomes: (1) for the 3-month HB, the phosphorylation levels of Akt I (p-Akt I) and p-mTOR decreased significantly compared to SA bats, but p-FoxO I levels remained unaltered; (2) for the TP-to-RA period, p-Akt I and p-FoxO I varied little, while p-mTOR showed biphasic oscillation; (3) proteolytic signals (i.e., atrogin-1, MuRF I, Skp2 and calpain-1) remained constant during the HB and TP-to-RA period. These results suggest that the resistive properties of torpid bat muscle against atrophy might be attained primarily by relatively constant proteolysis in combination with oscillatory anabolic activity (e.g., p-mTOR) corresponding to the frequency of arousals occurring throughout hibernation. J. Cell. Physiol. 222: 313-3 19, 2010. (C) 2009 Wiley-Liss, Inc.