Enhanced autophagy as a potential mechanism for the improved physiological function by simvastatin in muscular dystrophy.
Enhanced autophagy as a potential mechanism for the improved physiological function by simvastatin in muscular dystrophy.
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增强自噬是辛伐他汀在肌营养不良症中改善生理功能的潜在机制。
DOI：
10.1080/15548627.2016.1144005
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发表时间：
2016
期刊：
影响因子：
13.3
通讯作者：
Whitehead NP
中科院分区：
文献类型：
--
作者：
Whitehead NP
近年来，自噬已成为维持骨骼肌健康和功能的重要细胞过程。过度的自噬会引发肌肉分解代谢，导致肌肉萎缩。相反，自噬通量减少是几种肌肉疾病的特征，包括杜氏肌营养不良症，这是最常见和最严重的遗传性肌肉疾病。最近的证据表明，CYBB/NOX2增强活性氧（ROS）的产生会损害dmd/mdx小鼠（杜氏肌营养不良症的遗传模型）肌肉的自噬。他汀类药物降低骨骼肌CYBB/NOX2的表达和活性，刺激骨骼肌自噬。因此，我们用辛伐他汀治疗dmd/mdx小鼠，显示CYBB/ nox2介导的氧化应激降低，自噬诱导增强。这伴随着肌肉损伤、炎症和纤维化的减少，以及肌肉力量产生的增加。我们的数据表明，增加的自噬可能是辛伐他汀改善肌营养不良患者骨骼肌健康和功能的潜在机制。
Autophagy has recently emerged as an important cellular process for the maintenance of skeletal muscle health and function. Excessive autophagy can trigger muscle catabolism, leading to atrophy. In contrast, reduced autophagic flux is a characteristic of several muscle diseases, including Duchenne muscular dystrophy, the most common and severe inherited muscle disorder. Recent evidence demonstrates that enhanced reactive oxygen species (ROS) production by CYBB/NOX2 impairs autophagy in muscles from the dmd/mdx mouse, a genetic model of Duchenne muscular dystrophy. Statins decrease CYBB/NOX2 expression and activity and stimulate autophagy in skeletal muscle. Therefore, we treated dmd/mdx mice with simvastatin and showed decreased CYBB/NOX2-mediated oxidative stress and enhanced autophagy induction. This was accompanied by reduced muscle damage, inflammation and fibrosis, and increased muscle force production. Our data suggest that increased autophagy may be a potential mechanism by which simvastatin improves skeletal muscle health and function in muscular dystrophy.