Differential ubiquitin-proteasome and autophagy signaling following rotator cuff tears and suprascapular nerve injury.

Differential ubiquitin-proteasome and autophagy signaling following rotator cuff tears and suprascapular nerve injury.
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DOI:
10.1002/jor.22482
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发表时间:
2014-01
影响因子:
2.8
通讯作者:
Liu, Xuhui
Liu, Xuhui
中科院分区:
医学3区
文献类型:
--
作者:
Joshi, Sunil K.;Kim, Hubert T.;Feeley, Brian T.;Liu, Xuhui

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先前的研究评估了 Akt/mTOR 信号在肩袖肌肉萎缩中的作用,并确定肌腱横断 (TT) 和肩胛上神经 (SSN) 去神经 (DN) 后的信号传导存在差异,表明 TT 和 DN 后的萎缩是由不同的蛋白质降解途径调节的。在这项研究中,在 TT 和 DN 后评估了两种肌肉蛋白水解系统,即泛素蛋白酶体途径和自噬,这两种系统已被证明是其他损伤模型中肌肉萎缩的有效调节剂。除了检查蛋白质降解之外,本研究还评估了这两种手术模型的蛋白质合成率,以了解蛋白质降解和合成之间的平衡如何导致肩袖损伤后的萎缩。与肌肉萎缩期间蛋白质合成减少的传统理论相反,这项研究表明,两种手术模型后,肩袖肌肉萎缩中蛋白质合成均上调。虽然泛素-蛋白酶体途径是 DN 后出现的萎缩的主要因素,但自噬是 TT 后出现的萎缩的主要因素。这项研究的结果表明,蛋白质降解是导致肩袖损伤后萎缩的主要因素。然而,如果涉及 SSN 损伤,则会激活不同的蛋白水解途径。
Previous studies have evaluated role of Akt/mTOR signaling in rotator cuff muscle atrophy and determined that there was differential in signaling following tendon transection (TT) and suprascapular nerve (SSN) denervation (DN), suggesting that atrophy following TT and DN was modulated by different protein degradation pathways. In this study, two muscle proteolytic systems that have been shown to be potent regulators of muscle atrophy in other injury models, the ubiquitin-proteasome pathway and autophagy, were evaluated following TT and DN. In addition to examining protein degradation, this study assessed protein synthesis rate following these two surgical models to understand how the balance between protein degradation and synthesis results in atrophy following rotator cuff injury. In contrast to the traditional theory that protein synthesis is decreased during muscle atrophy, this study suggests that protein synthesis is up-regulated in rotator cuff muscle atrophy following both surgical models. While the ubiquitin-proteasome pathway was a major contributor to the atrophy seen following DN, autophagy was a major contributor following TT. The findings of this study suggest that protein degradation is the primary factor contributing to atrophy following rotator cuff injury. However, different proteolytic pathways are activated if SSN injury is involved.
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