Oxidative stress, an imbalance of redox homeostasis, contributes to the pathogenesis and progress of muscle atrophy. However, it is debated whether oxidative stress is a cause or consequence of muscle atrophy. In this study, we investigated the relationship between menadione‐induced oxidative stress and serum starvation‐induced muscle atrophy in C2C12 myotubes. We found that atrophic phenotypes including myotube diameter decrease, protein ubiquitination, and the expression of atrogenes were detected under oxidative stress as well as during serum starvation. Oxidative stress during serum starvation was assessed to confirm the correlation. Both intracellular reactive oxygen species (ROS) and protein oxidation were increased in atrophic myotubes. These results indicate that menadione‐induced oxidative stress triggers muscle atrophy and vice versa. Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a key regulator of cellular response to oxidative stress and it is considered to have a cytoprotective role in the mitigation of muscle atrophy. Transcription of heme oxygenase‐1 (HO‐1) and NAD(P)H quinone dehydrogenase‐1, target genes of Nrf2, was decreased during serum starvation, which is related to decreased nuclear translocation of Nrf2. Pre‐treatment of sulforaphane (SFN), a known Nrf2 inducer, before serum starvation showed a protective effect via Nrf2/HO‐1 upregulation. SFN can liberate Nrf2 from Keap1, enabling the nuclear translocation of Nrf2. Consequently, the expression of HO‐1 increased and intracellular ROS was significantly reduced by SFN pre‐treatment. These results demonstrate that oxidative stress mediates the pathophysiology of muscle atrophy, which can be improved via upregulation of the Nrf2‐mediated antioxidant response.

中文翻译：

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萝卜硫素通过激活培养的C2C12细胞中的Nrf2途径改善了血清饥饿引起的肌肉萎缩。

氧化应激是氧化还原体内稳态的失衡，有助于肌肉萎缩的发生和发展。然而，人们争论氧化应激是肌肉萎缩的原因还是后果。在这项研究中，我们调查了甲萘醌诱导的氧化应激与C2C12肌管中血清饥饿引起的肌肉萎缩之间的关系。我们发现在氧化应激下以及血清饥饿期间检测到萎缩表型，包括肌管直径减少，蛋白质泛素化和星形胶质基因的表达。评估血清饥饿期间的氧化应激以确认相关性。萎缩性肌管中细胞内活性氧（ROS）和蛋白质氧化均增加。这些结果表明，甲萘醌诱导的氧化应激会触发肌肉萎缩，反之亦然。核因子类胡萝卜素2相关因子2（Nrf2）是细胞对氧化应激反应的关键调节因子，被认为在缓解肌肉萎缩中具有细胞保护作用。Nrf2的靶基因血红素加氧酶-1（HO-1）和NAD（P）H醌脱氢酶-1的转录在血清饥饿期间减少，这与Nrf2的核易位减少有关。在血清饥饿之前，对萝卜硫素（SFN）（一种已知的Nrf2诱导剂）进行预处理可通过Nrf2 / HO-1上调显示出保护作用。SFN可以从Keap1中释放Nrf2，从而实现Nrf2的核易位。因此，通过SFN预处理，HO-1的表达增加并且细胞内ROS显着降低。这些结果表明，氧化应激介导了肌肉萎缩的病理生理，