Skeletal muscle atrophy: disease-induced mechanisms may mask disuse atrophy
Skeletal muscle atrophy: disease-induced mechanisms may mask disuse atrophy
复制标题
DOI：
10.1007/s10974-015-9439-8
复制
发表时间：
2015-12-01
影响因子：
2.7
通讯作者：
Karatzaferi, C.
中科院分区：
文献类型：
--
作者：
Malavaki, C. J.;Sakkas, G. K.;Karatzaferi, C.
废用性萎缩是由于不活动或低于“正常”使用而导致的骨骼肌质量损失。它不仅是“现代”久坐不动生活方式的一个秘密组成部分，也是许多病理学的一部分，其中肌肉损失与疾病特异性和/或其他毒性因素有关，最终导致消耗（恶病质）。无论是废用还是疾病引起的，肌肉损失都会导致虚弱和代谢合并症，并带来高昂的社会和经济成本。这篇综述讨论了相互作用的信号通路的复杂网络，包括Atrogin-1/MAFbx，IGF 1-Akt，肌肉生长抑制素，糖皮质激素，NF-κ B B，MAPK和半胱天冬酶，似乎调节废用性萎缩，但也有共同的激活模式，在其他状态的肌肉损失，如肌肉减少症或恶病质。活性氧也是细胞信号传导途径的重要调节剂，可以加速蛋白质水解和抑制蛋白质合成。运动是一种有效的对策，抗氧化剂可能会显示出一些好处。我们讨论了如何使用的实验模型可以至关重要地影响结果，因此我们对萎缩的理解。采样的时间是至关重要的，因为一些信号机制在萎缩过程中早期达到峰值，然后迅速下降，而其他信号机制甚至在研究开始后数周和数月仍呈现高水平。这种差异的重要性在于今后考虑适当的治疗目标。除了试图纠正缺陷基因或否定其影响外，新的理性方式的技术进步应该旨在在精确的时间点调节特定的基因表达，以根据萎缩诱导的起源在治疗方案中治疗肌肉萎缩。
Disuse atrophy is the loss of skeletal muscle mass due to inactivity or lower than 'normal' use. It is not only a furtive component of the 'modern' sedentary lifestyle but also a part of numerous pathologies, where muscle loss is linked to disease specific and/or other toxicity factors, eventually leading to wasting (cachexia). Whether disuse-or-disease induced, muscle loss leads to weakness and metabolic comorbidities with a high societal and financial cost. This review discusses the intricate network of interacting signalling pathways including Atrogin-1/MAFbx, IGF1-Akt, myostatin, glucocorticoids, NF-kappa B, MAPKs and caspases that seem to regulate disuse atrophy but also share common activation patterns in other states of muscle loss such as sarcopenia or cachexia. Reactive oxygen species are also important regulators of cell signalling pathways that can accelerate proteolysis and depress protein synthesis. Exercise is an effective countermeasure and antioxidants may show some benefit. We discuss how the experimental model used can crucially affect the outcome and hence our understanding of atrophy. Timing of sampling is crucial as some signalling mechanisms reach their peak early during the atrophy process to rapidly decline thereafter, while other present high levels even weeks and months after study initiation. The importance of such differences lays in future consideration of appropriate treatment targets. Apart from attempting to correct defective genes or negate their effects, technological advances in new rational ways should aim to regulate specific gene expression at precise time points for the treatment of muscle atrophy in therapeutic protocols depending on the origin of atrophy induction.