The duration of glucocorticoid treatment alters the anabolic response to high-force muscle contractions.
The duration of glucocorticoid treatment alters the anabolic response to high-force muscle contractions.
复制标题
糖皮质激素治疗的持续时间会改变对高强度肌肉收缩的合成代谢反应。
DOI：
10.1152/japplphysiol.00113.2023
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Gordon,BradleyS
中科院分区：
文献类型：
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作者：
Dunlap,KirstenR;Steiner,JenniferL;Hickner,RobertC;Chase,PBryant;Gordon,BradleyS
糖皮质激素会引起肌病，包括肌肉质量和力量的损失。抗阻运动可以逆转肌肉损失，因为它诱导了一种合成代谢反应，其特征是增加肌肉蛋白质合成并潜在地抑制蛋白质分解。抗阻运动是否诱导糖皮质激素肌病肌肉的合成代谢反应是未知的，这是一个问题，因为长期糖皮质激素暴露改变了基因的表达，这些基因可能通过限制途径的激活来阻止合成代谢反应，例如复合物1中雷帕霉素的机制靶点（mTORC 1）。本研究的目的是评估高强度收缩是否启动糖皮质激素肌病肌肉的合成代谢反应。通过用地塞米松（DEX）处理雌性小鼠7天或15天来分析合成代谢反应。治疗后，通过电刺激坐骨神经使所有小鼠的左胫骨前肌收缩。收缩后4小时收获肌肉。使用SUnSET方法估计肌肉蛋白质合成速率。治疗7天后，两组的高强度收缩增加了蛋白质合成和mTORC 1信号传导。治疗15天后，两组小鼠的高强度收缩激活了mTORC 1信号，但对照组小鼠的蛋白质合成仅增加。未能增加蛋白质合成可能是因为DEX治疗小鼠的基线合成速率升高。自噬的LC 3 II/I比率标记物通过收缩而降低，而与治疗持续时间无关。这些数据表明糖皮质激素治疗的持续时间改变了对强力收缩的合成代谢反应。新&值得注意的是糖皮质激素肌病是最常见的、毒性的、非炎症性肌病。我们的工作表明，高强度收缩增加蛋白质合成骨骼肌短期糖皮质激素治疗后。然而，较长持续时间的糖皮质激素治疗导致合成代谢抵抗高力收缩，尽管激活的机械目标雷帕霉素在复合物1（mTORC 1）信号通路。这项工作定义了高力量收缩激活过程的潜在限制，这些过程将恢复糖皮质激素肌病患者失去的肌肉质量。
Glucocorticoids induce a myopathy that includes loss of muscle mass and strength. Resistance exercise may reverse the muscle loss because it induces an anabolic response characterized by increases in muscle protein synthesis and potentially suppressing protein breakdown. Whether resistance exercise induces an anabolic response in glucocorticoid myopathic muscle is unknown, which is a problem because long-term glucocorticoid exposure alters the expression of genes that may prevent an anabolic response by limiting activation of pathways such as the mechanistic target of rapamycin in complex 1 (mTORC1). The purpose of this study was to assess whether high-force contractions initiate an anabolic response in glucocorticoid myopathic muscle. The anabolic response was analyzed by treating female mice with dexamethasone (DEX) for 7 days or 15 days. After treatment, the left tibialis anterior muscle of all mice was contracted via electrical stimulation of the sciatic nerve. Muscles were harvested 4 h after contractions. Rates of muscle protein synthesis were estimated using the SUnSET method. After 7 days of treatment, high-force contractions increased protein synthesis and mTORC1 signaling in both groups. After 15 days of treatment, high-force contractions activated mTORC1 signaling equally in both groups, but protein synthesis was only increased in control mice. The failure to increase protein synthesis may be because baseline synthetic rates were elevated in DEX-treated mice. The LC3 II/I ratio marker of autophagy was decreased by contractions regardless of treatment duration. These data show duration of glucocorticoid treatment alters the anabolic response to high-force contractions.NEW & NOTEWORTHYGlucocorticoid myopathy is the most common, toxic, noninflammatory myopathy. Our work shows that high-force contractions increase protein synthesis in skeletal muscle following short-term glucocorticoid treatment. However, longer duration glucocorticoid treatment results in anabolic resistance to high-force contractions despite activation of the mechanistic target of rapamycin in complex 1 (mTORC1) signaling pathway. This work defines potential limits for high-force contractions to activate the processes that would restore lost muscle mass in glucocorticoid myopathic patients.