HDACs in skeletal muscle remodeling and neuromuscular disease.
HDACs in skeletal muscle remodeling and neuromuscular disease.
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DOI：
10.1007/978-3-642-21631-2_5
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发表时间：
2011
影响因子：
--
通讯作者：
Bryan J. Simmons;T. Cohen;R. Bedlack;T. Yao
中科院分区：
文献类型：
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作者：
Bryan J. Simmons;T. Cohen;R. Bedlack;T. Yao
骨骼肌是由具有不同收缩和代谢特性的异质性肌纤维组成的。肌纤维的多种功能使骨骼肌能够执行从保持身体姿势到执行主动运动的不同任务。除了运动性，占身体质量40%的骨骼肌也是胰岛素作用的关键靶点，并在葡萄糖代谢中发挥重要作用。成人骨骼肌是一个高度适应性的器官系统，可以经历特定的收缩和代谢特性的变化，以满足不同的功能需求。肌纤维的这种可塑性反映了由神经活动控制的基因表达程序的高度协调变化。按需重塑的能力赋予骨骼肌对动物生存至关重要的显著适应性;然而，其失调可能导致肌肉和代谢疾病。神经活动如何决定转录编程来修改肌肉功能和多样性是一个根本问题。最近的研究已经确定IIa类HDAC的成员在生理和病理肌肉重塑中作为重要的效应物。通过改变肌纤维性质，IIa HDAC活性的药理学操纵在肌肉疾病的治疗中可能具有潜在的治疗效用。
Skeletal muscle is made of heterogeneous myofibers with different contractile and metabolic properties. The diverse functionality of myofibers enables skeletal muscle to carry out different tasks from maintaining body posture to performing active movements. In addition to motility, skeletal muscle, which constitutes 40% of body mass, is also a key target of insulin action and performs an essential function in glucose metabolism. Adult skeletal muscle is a highly adaptive organ system and can undergo specific changes in contractile and metabolic properties to meet different functional demands. This plasticity of myofibers reflects a highly coordinated change in gene expression program that is controlled by neural activity. The capacity for on-demand remodeling confers skeletal muscle the remarkable adaptability important for animal survival; its dysregulation, however, could contribute to muscle and metabolic diseases. How neural activity dictates transcriptional programming to modify muscle functionality and diversity is a fundamental issue. Recent studies have identified members of class IIa HDACs as important effectors in both physiological and pathological muscle remodeling. By way of modifying myofiber properties, pharmacological manipulation of IIa HDACs activity could have potential therapeutic utility in the treatment of muscle disorders.