Muscle-specific and age-related changes in protein synthesis and protein degradation in response to hindlimb unloading in rats
Muscle-specific and age-related changes in protein synthesis and protein degradation in response to hindlimb unloading in rats
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DOI：
10.1152/japplphysiol.00703.2016
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发表时间：
2017-05-01
影响因子：
3.3
通讯作者：
Bodine, Sue C.
中科院分区：
文献类型：
--
作者：
Baehr, Leslie M.;West, Daniel W. D.;Bodine, Sue C.
废用是肌肉萎缩的有力诱因，但驱动这种肌肉质量损失的分子机制存在高度争议。特别是，废弃触发蛋白质合成减少或蛋白质降解增加的程度，以及这些变化在肌肉中是均匀的还是受年龄的影响，目前尚不清楚。我们的目的是确定废用对成年和老年大鼠不同功能和纤维类型下肢肌肉蛋白质合成和蛋白质降解的影响。在后肢卸载（HU） 3、7、14天后，测量成年和老年大鼠比目鱼肌、腓肠肌内侧和胫前肌（TA）中蛋白质合成和降解的变化。在卸荷期间，肌肉质量的损失是进行性的，但在肌肉类型和年龄之间变化很大（- 9%至-38%）。除老TA外，所有肌肉的蛋白质合成均显著降低。萎缩相关基因的表达与蛋白质降解仅存在松散关联，所有肌肉中RING finger-1、肌肉萎缩F-box （MAFbx）和Forkhead box O1的表达均显著增加，但蛋白酶体活性仅在成人比目鱼中增加。与成年肌肉相比，老年肌肉中的MAFbx蛋白水平明显更高，尽管老年人的microRNA-23a表达更高。这些结果表明，成人和老年肌肉对HU的反应相似，由于蛋白质合成减少和蛋白质降解增加，肌肉质量的最大损失主要发生在慢抽搐伸肌中。在这项研究中，我们发现年龄并没有加剧大鼠对卸载的萎缩反应，相反，萎缩的程度在肌肉中是高度可变的，这表明蛋白质合成和蛋白质降解的变化以肌肉特异性的方式发生。我们的数据强调了在多个时间点研究不同纤维类型和生理功能的肌肉的重要性，以充分了解导致废用性萎缩的分子机制。
Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss of muscle mass are highly debated. In particular, the extent to which disuse triggers decreases in protein synthesis or increases in protein degradation, and whether these changes are uniform across muscles or influenced by age, is unclear. We aimed to determine the impact of disuse on protein synthesis and protein degradation in lower limb muscles of varied function and fiber type in adult and old rats. Alterations in protein synthesis and degradation were measured in the soleus, medial gastrocnemius, and tibialis anterior (TA) muscles of adult and old rats subjected to hindlimb unloading (HU) for 3, 7, or 14 days. Loss of muscle mass was progressive during the unloading period, but highly variable (-9 to -38%) across muscle types and between ages. Protein synthesis decreased significantly in all muscles, except for the old TA. Atrophy-associated gene expression was only loosely associated with protein degradation as muscle RING finger-1, muscle atrophy F-box (MAFbx), and Forkhead box O1 expression significantly increased in all muscles, but an increase in proteasome activity was only observed in the adult soleus. MAFbx protein levels were significantly higher in the old muscles compared with adult muscles, despite the old having higher expression of microRNA-23a. These results indicate that adult and old muscles respond similarly to HU, and the greatest loss in muscle mass occurs in predominantly slow-twitch extensor muscles due to a concomitant decrease in protein synthesis and increase in protein degradation.NEW & NOTEWORTHY In this study, we showed that age did not intensify the atrophy response to unloading in rats, but rather that the degree of atrophy was highly variable across muscles, indicating that changes in protein synthesis and protein degradation occur in a muscle-specific manner. Our data emphasize the importance of studying muscles of varying fiber-type and physiological function at multiple time points to fully understand the molecular mechanisms responsible for disuse atrophy.