Remarkable preservation of Ca(2+) homeostasis and inhibition of apoptosis contribute to anti-muscle atrophy effect in hibernating Daurian ground squirrels.

Remarkable preservation of Ca(2+) homeostasis and inhibition of apoptosis contribute to anti-muscle atrophy effect in hibernating Daurian ground squirrels.
复制标题

显着保持 Ca2 稳态和抑制细胞凋亡有助于冬眠达乌尔地松鼠的抗肌肉萎缩作用

DOI:
10.1038/srep27020
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发表时间:
2016-06-03
期刊:
影响因子:
4.6
通讯作者:
Gao Y
Gao Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fu W;Hu H;Dang K;Chang H;Du B;Wu X;Gao Y

文献摘要

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冬眠动物在长时间的冬眠不活动中偏离肌肉萎缩的潜在机制仍然是难以捉摸的。本研究验证了这一假设,即细胞内Ca 2+稳态的维持和细胞凋亡的抑制将负责防止冬眠的达乌尔黄鼠肌肉萎缩。结果表明,冬眠和冬眠后比目鱼肌和趾长伸肌(EDL)胞内Ca 2+维持稳态,而腓肠肌(GAS)胞内Ca 2+超载,冬眠后恢复。在间歇性觉醒时,三种肌均出现Ca ~(2+)超载。此外,Bax/Bcl-2比值在冬眠前、冬眠和苏醒间期的转录水平上没有变化,在冬眠后降至最低。Bax/Bcl-2比值在冬眠时降低,而在觉醒时恢复。细胞色素C在冬眠后的GAS和EDL中表达增加,但TUNEL法未观察到细胞凋亡。这些结果表明,冬眠时细胞内Ca ~(2+)的稳态可能是由间歇唤醒时细胞内Ca ~(2+)超载调节的,这可能是通过抑制细胞凋亡来防止肌萎缩的机制之一。此外,肌肉特异性表明,不同的肌肉在冬眠中可能参与不同的机制来对抗废用性萎缩。
The underlying mechanisms that hibernators deviated from muscle atrophy during prolonged hibernating inactivity remain elusive. This study tested the hypothesis that the maintenance of intracellular Ca2+ homeostasis and inhibition of apoptosis would be responsible for preventing muscle atrophy in hibernating Daurian ground squirrels. The results showed that intracellular Ca2+ homeostasis was maintained in soleus and extensor digitorum longus (EDL) in hibernation and post-hibernation, while cytosolic Ca2+ was overloaded in gastrocnemius (GAS) in hibernation with a recovery in post-hibernation. The Ca2+ overload was also observed in interbout arousals in all three type muscles. Besides, the Bax/Bcl-2 ratio was unchanged in transcriptional level among pre-hibernation, hibernation and interbout arousals and reduced to a minimum in post-hibernation. Furthermore, the Bax/Bcl-2 ratio in protein level was reduced in hibernation but recovered in interbout arousals. Although cytochrome C was increased in GAS and EDL in post-hibernation, no apoptosis was observed by TUNEL assay. These findings suggested that the intracellular Ca2+ homeostasis in hibernation might be regulated by the cytosolic Ca2+ overload during interbout arousals, which were likely responsible for preventing muscle atrophy via inhibition of apoptosis. Moreover, the muscle-specificity indicated that the different mechanisms against disuse-induced atrophy might be involved in different muscles in hibernation.