Ambient hypoxia enhances the loss of muscle mass after extensive injury.
Ambient hypoxia enhances the loss of muscle mass after extensive injury.
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DOI：
10.1007/s00424-013-1336-7
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发表时间：
2014-03
期刊：
影响因子：
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通讯作者：
Bigard X
中科院分区：
文献类型：
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作者：
Chaillou T;Koulmann N;Meunier A;Pugnière P;McCarthy JJ;Beaudry M;Bigard X
缺氧在体外诱导骨骼肌质量损失并改变肌肉发生，但是否影响损伤后的体内肌肉再生仍有待阐明。我们假设缺氧会损害再生过程中肌肉质量的恢复。为了验证这一假设，雌性大鼠的比目鱼肌在诺特辛损伤后，在常氧或低氧（5,500 m）条件下恢复3、7、14和28天。缺氧损害了新肌纤维的形成和生长，并在再生的前7天增加了肌肉质量的损失，但不影响28天肌肉质量的最终恢复。通过p70S6K和4E-BP1磷酸化评估，缺氧条件下再生受损与雷帕霉素机械靶标（mTOR）信号的钝化激活有关，而p70S6K和4E-BP1磷酸化独立于Akt激活。缺氧时mTOR活性的降低与amp激活的蛋白激酶活性的升高一致，但与发育调节和DNA应答1蛋白含量的变化无关。缺氧使再生7天后萎缩肌环指-1 mRNA水平升高，但萎缩肌F盒转录物水平保持不变。缺氧后第7天，MyoD和myogenin mRNA表达随再生的增加有所减弱。总之，我们的研究结果支持这样一种观点，即在缺氧条件下再生1周后观察到的肌肉质量损失增加，主要是由于蛋白质合成和卫星细胞活性降低导致新纤维的形成和生长受损。
Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro, but whether it affects muscle regeneration in vivo following injury remains to be elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass during regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14, and 28 days under normoxia or hypobaric hypoxia (5,500 m) conditions. Hypoxia impaired the formation and growth of new myofibers and enhanced the loss of muscle mass during the first 7 days of regeneration, but did not affect the final recovery of muscle mass at 28 days. The impaired regeneration under hypoxic conditions was associated with a blunted activation of mechanical target of rapamycin (mTOR) signaling as assessed by p70S6K and 4E-BP1 phosphorylation that was independent of Akt activation. The decrease in mTOR activity with hypoxia was consistent with the increase in AMP-activated protein kinase activity, but not related to the change in regulated in development and DNA response 1 protein content. Hypoxia increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of regeneration, though muscle atrophy F box transcript levels remained unchanged. The increase in MyoD and myogenin mRNA expression with regeneration was attenuated at 7 days with hypoxia. In conclusion, our results support the notion that the enhanced loss of muscle mass observed after 1 week of regeneration under hypoxic conditions could mainly result from the impaired formation and growth of new fibers resulting from a reduction in protein synthesis and satellite cell activity.