Signaling mechanisms involved in disuse muscle atrophy
Signaling mechanisms involved in disuse muscle atrophy
复制标题
废用性肌肉萎缩涉及的信号机制
DOI：
10.1016/j.mehy.2006.11.043
复制
发表时间：
2007-01-01
影响因子：
4.7
通讯作者：
Fan, Ming
中科院分区：
文献类型：
--
作者：
Zhang, Peng;Chen, Xiaoping;Fan, Ming
由于卧床休息、失神经、后肢卸载、制动或微重力导致骨骼肌长时间不活动，可能会导致严重的肌肉萎缩。肌肉萎缩的特征是肌肉纤维横截面积和蛋白质含量减少，力量减弱，胰岛素抵抗增加，以及从慢纤维类型向快纤维类型的转变。蛋白质合成的减少和蛋白质降解率的增加是由于停用而导致的肌肉蛋白质快速损失的主要原因。然而，我们才刚刚开始更多地关注与触发对身体不活动/微重力的初始反应有关的基因的识别。本文主要介绍废用性萎缩过程中蛋白质丢失的信号转导途径，包括最近发现的两种泛素连接酶：肌肉环指1(MuRF1)和肌肉萎缩F-box(MAFbx)。最近的报道表明，肌肉中IGF-1/Pl3K/Akt通路的抑制可能参与了废用性萎缩的进展。核因子-kappaB可能是废用性萎缩的关键细胞内信号转导因子。在特定条件下，肌肉抑制素、p38和钙调神经磷酸酶等因子可以诱导肌肉蛋白质丢失，但它们是否是废用性萎缩的必要成分，还需要进一步的实验来确定。在可能的情况下，也讨论了萎缩肌肉从慢到快纤维类型转变和胰岛素抵抗增加的分子机制。总的来说，废用引起的肌肉萎缩是一个高度有序的过程，由细胞内信号通路之间的相互作用控制，而不是孤立的通路。(C)2007爱思唯尔有限公司。保留所有权利。
Prolonged periods of skeletal muscle inactivity due to bed rest, denervation, hindlimb unloading, immobilization, or microgravity, can result in significant muscle atrophy. The muscle atrophy is characterized as decreased muscle fiber cross-sectional area and protein content, reduced force, increased insulin resistance as well as a slow to fast fiber type transition. The decreases in protein synthesis and increases in protein degradation rates account for the majority of the rapid Loss of muscle protein due to disuse. However, we are just beginning to pay more attention on the identification of genes involved in triggering initial responses to physical inactivity/ microgravity. Our review mainly focuses on the signaling pathways involved in protein loss during disuse atrophy, including two recently identified ubiquitin ligases: muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx). Recent reports suggest that inhibition of the IGF-1 /Pl3K/Akt pathway in muscle may be involved in the progression of disuse atrophy. NF-kappa B seems to be a key intracellular signal transducer in disuse atrophy. Factors such as myostatin, p38 and calcineurin can induce muscle protein loss under specified conditions, but further experiments are needed to determine whether they are necessary components of disuse atrophy. Where possible, the molecular mechanisms underlying the slow to fast fiber type transition and increased insulin resistance in atrophic muscles are discussed as well. Collectively, the disuse-induced muscle atrophy is a highly ordered process that is controlled by interactions between intracellular signaling pathways rather than isolated pathways. (c) 2007 Elsevier Ltd. All rights reserved.