Transforming growth factor type beta (TGF-β) requires reactive oxygen species to induce skeletal muscle atrophy
Transforming growth factor type beta (TGF-β) requires reactive oxygen species to induce skeletal muscle atrophy
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DOI：
10.1016/j.cellsig.2016.01.010
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发表时间：
2016-05-01
影响因子：
4.8
通讯作者：
Cabello-Verrugio, Claudio
中科院分区：
文献类型：
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作者：
Abrigo, Johanna;Carlos Rivera, Juan;Cabello-Verrugio, Claudio
转化生长因子β 1 （tgf - β 1）是骨骼肌的经典调节剂，在骨骼肌疾病中调节多种过程，如肌肉发生、再生和肌肉功能。骨骼肌萎缩的特征是肌肉力量和质量的损失，是由tgf - β调节的病理条件之一。萎缩还会导致肌球蛋白重链（MHC）降解增加，以及两种肌肉特异性E3泛素连接酶atrogin-1和MuRF-1的表达增加。活性氧（ROS）是肌肉萎缩的调节剂，NAD(P)H氧化酶（NOX）是ROS的主要来源之一。虽然最近发现tgf - β 1诱导骨骼肌萎缩，但其潜在机制尚不完全清楚。本研究评估了一氧化氮来源的活性氧在tgf - β诱导的骨骼肌萎缩中的作用。tgf - β 1诱导C2C12肌管萎缩，肌管直径减小，MHC水平降低，MuRF-1水平升高。同时，tgf - β增加了nox诱导的ROS含量。有趣的是，通过罗布酚和n -乙酰半胱氨酸（NAC）抗氧化处理抑制NOX可以降低肌管中增加的ROS水平。此外，夹竹桃素和NAC均能完全阻止tgf - β诱导的MHC降低、肌管直径减小和MuRF-1升高。向胫骨前肌注射tgf - β 1诱导萎缩，观察到纤维直径和MHC水平下降，同时MuRF-1水平升高。同样，tgf - β增加了骨骼肌较小纤维中的ROS含量。此外，给予小鼠MAC可阻止所有萎缩效应和tgf - β诱导的胫骨前肌ROS的增加。这是首次报道tgf - β在骨骼肌中依赖于nox诱导的ROS具有萎缩作用的研究。(C) 2016 Elsevier Inc.版权所有。
Transforming growth factor beta 1 (TGF-beta 1) is a classical modulator of skeletal muscle and regulates several processes, such as myogenesis, regeneration, and muscle function in skeletal muscle diseases. Skeletal muscle atrophy, characterised by the loss of muscle strength and mass, is one of the pathological conditions regulated by TGF-beta. Atrophy also results in increased myosin heavy chain (MHC) degradation and the expression of two muscle-specific E3 ubiquitin ligases, atrogin-1 and MuRF-1. Reactive oxygen species (ROS) are modulators of muscle wasting, and NAD(P)H oxidase (NOX) is one of the main sources of ROS. While it was recently found that TGF-beta 1 induces atrophy in skeletal muscle, the underlying mechanism is not fully understood. In this study, the role of NOX-derived ROS in skeletal muscle atrophy induced by TGF-beta was assessed. TGF-beta 1 induced an atrophic effect in C2C12 myotubes, as evidenced by decreased myotube diameter and MHC levels, together with increased MuRF-1 levels. Concomitantly, TGF-beta increased NOX-induced ROS contents. Interestingly, NOX inhibition through apocynin and the antioxidant treatment with N-acetyl cysteine (NAC) decreased increased ROS levels in myotubes. Additionally, both apocynin and NAC completely prevented the decreased MHC, decreased myotube diameter, and increased MuRF-1 induced by TGF-beta. Injection of TGF-beta 1 into the tibialis anterior muscle induced atrophy, as observed by decreased fibre diameter and MHC levels, together with increased MuRF-1 levels. Likewise, TGF-beta increased the ROS contents in the smaller fibres of skeletal muscle. Additionally, the administration of MAC to mice prevented all atrophic effects and the increase in ROS induced by TGF-beta in the tibialis anterior. This is the first study to report that TGF-beta has an atrophic effect dependent on NOX-induced ROS in skeletal muscle. (C) 2016 Elsevier Inc. All rights reserved.