Stable atrogin-1 (Fbxo32) and MuRF1 (Trim63) gene expression is involved in the protective mechanism in soleus muscle of hibernating Daurian ground squirrels (Spermophilus dauricus).
Stable atrogin-1 (Fbxo32) and MuRF1 (Trim63) gene expression is involved in the protective mechanism in soleus muscle of hibernating Daurian ground squirrels (Spermophilus dauricus).
复制标题
稳定的 atrogin-1 (Fbxo32) 和 MuRF1 (Trim63) 基因表达参与冬眠达乌尔地松鼠 (Spermophilus dauricus) 比目鱼肌的保护机制
DOI：
10.1242/bio.015776
复制
发表时间：
2016-01-06
期刊：
影响因子：
2.4
通讯作者：
Gao YF
中科院分区：
文献类型：
--
作者：
Dang K;Li YZ;Gong LC;Xue W;Wang HP;Goswami N;Gao YF
摘要了解冬眠动物在长时间不活动时防止或限制肌肉萎缩的机制对治疗具有重要意义。我们研究了外部因素是否会影响调节蛋白质合成和降解的途径，从而导致达乌尔黄鼠（Spermophilus dauricus）肌肉萎缩的预防。研究了不同季节14 d的后肢去负荷（HU）和2个月的冬眠对比目鱼肌（SOL）湿重、肌体比、肌纤维横截面积（CSA）、肌纤维分布和肌超微结构的影响。我们还测量了Akt，mTOR和FoxO 1的蛋白表达和激活状态以及atrogin-1和MuRF 1的mRNA表达的变化。与对照组相比，秋冬季HU显著降低SOL肌肉湿质量和肌体质量比，降低I型和II型纤维CSA，并导致超微结构异常。而这些指标在冬眠前和冬眠组之间没有变化。HU后Akt和mTOR的磷酸化水平显著降低，FoxO 1的磷酸化水平和atrogin-1和MuRF 1的mRNA表达增加。在冬眠过程中，Akt和mTOR的磷酸化水平显著降低，而FoxO 1的磷酸化水平以及atrogin-1和MuRF 1的mRNA表达水平保持不变。总的来说，我们的研究结果表明，废用和季节性可能不足以启动先天的保护机制，防止SOL萎缩在长时间的冬眠不活动。atrogin-1和MuRF 1的稳定表达可能通过控制冬眠期间肌肉蛋白的泛素化来防止SOL萎缩。总结：atrogin-1和MuRF 1的mRNA表达在达乌尔黄鼠冬眠期间保持不变，表明这些基因的稳定表达可能有助于通过控制冬眠期间肌肉蛋白的泛素化来防止SOL萎缩。
ABSTRACT Understanding the mechanisms that protect against or limit muscle atrophy in hibernators during prolonged inactivity has important implications for its treatment. We examined whether external factors influence the pathways regulating protein synthesis and degradation, leading to muscle atrophy prevention in Daurian ground squirrels (Spermophilus dauricus). We investigated the effects of 14-day hindlimb-unloading (HU) in different seasons and two-month hibernation on the soleus (SOL) muscle wet mass, muscle-to-body mass ratio, fiber cross sectional area (CSA), fiber distribution and muscle ultrastructure. We also measured changes in the protein expression and activation states of Akt, mTOR and FoxO1 and the mRNA expression of atrogin-1 and MuRF1. Compared with the control groups, autumn and winter HU significantly lowered SOL muscle wet mass and muscle-to-body mass ratio, decreased type I and II fiber CSA and induced ultrastructural anomalies. However, these measured indices were unchanged between Pre-hibernation and Hibernation groups. Furthermore, phosphorylation levels of Akt and mTOR significantly decreased, while the phosphorylation level of FoxO1 and mRNA expression of atrogin-1 and MuRF1 increased after HU. During hibernation, the phosphorylation levels of Akt and mTOR significantly decreased, but the phosphorylation level of FoxO1 and mRNA expression of atrogin-1 and MuRF1 remained unchanged. Overall, our findings suggest that disuse and seasonality may not be sufficient to initiate the innate protective mechanism that prevents SOL atrophy during prolonged periods of hibernation inactivity. The stable expression of atrogin-1 and MuRF1 may facilitate to prevent SOL atrophy via controlling ubiquitination of muscle proteins during hibernation. Summary: mRNA expression of atrogin-1 and MuRF1 remains unchanged during hibernation of Daurian ground squirrels, suggesting that stable expression of these genes may facilitate the prevention of SOL atrophy via controlling ubiquitylation of muscle proteins during hibernation.