Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine.
Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine.
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DOI：
10.3390/medsci6010014
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发表时间：
2018-02-14
期刊：
影响因子：
--
通讯作者：
Mariottini P
中科院分区：
文献类型：
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作者：
Cervelli M;Leonetti A;Duranti G;Sabatini S;Ceci R;Mariottini P
骨骼肌约占总体质量的 40%。保持肌肉健康和功能对于整个身体至关重要，以对抗 II 型糖尿病、心血管疾病和癌症等慢性疾病。长期缺乏身体活动，尤其是老年人，会导致肌肉萎缩，这是一种病理状态，会带来生活质量差、身体残疾和高死亡率等不良后果。在小鼠骨骼肌 C2C12 细胞中，在细胞分化过程中发现精胺氧化酶 (SMOX) 的表达增加。值得注意的是，SMOX 过度表达会增加肌纤维尺寸，而 SMOX 减少足以在多种小鼠模型中诱导肌肉萎缩。值得注意的是，SMOX 反应产物亚精胺似乎与骨骼肌萎缩/肥大有关。它可以有效地重新激活自噬，改善 VI 型胶原缺失小鼠的肌病缺陷。此外，亚精胺治疗如果与运动相结合，可以影响 D-gal 诱导的与衰老相关的骨骼肌萎缩。这篇综述假设了 SMOX 在骨骼肌分化过程中的作用，并概述了它和亚精胺在肌肉萎缩中的作用。鉴定参与维持骨骼肌健康的新分子途径可能有助于开发治疗肌肉萎缩的新型治疗先导化合物。
Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly, causes muscle atrophy, a pathological state with adverse outcomes such as poor quality of life, physical disability, and high mortality. In murine skeletal muscle C2C12 cells, increased expression of the spermine oxidase (SMOX) enzyme has been found during cell differentiation. Notably, SMOX overexpression increases muscle fiber size, while SMOX reduction was enough to induce muscle atrophy in multiple murine models. Of note, the SMOX reaction product spermidine appears to be involved in skeletal muscle atrophy/hypertrophy. It is effective in reactivating autophagy, ameliorating the myopathic defects of collagen VI-null mice. Moreover, spermidine treatment, if combined with exercise, can affect D-gal-induced aging-related skeletal muscle atrophy. This review hypothesizes a role for SMOX during skeletal muscle differentiation and outlines its role and that of spermidine in muscle atrophy. The identification of new molecular pathways involved in the maintenance of skeletal muscle health could be beneficial in developing novel therapeutic lead compounds to treat muscle atrophy.