Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading.
Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading.
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DOI：
10.1152/ajpregu.00688.2004
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发表时间：
2005-05
期刊：
影响因子：
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通讯作者：
T. Sugiura;N. Abe;Mai Nagano;K. Goto;K. Sakuma;H. Naito;T. Yoshioka;S. Powers
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文献类型：
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作者：
T. Sugiura;N. Abe;Mai Nagano;K. Goto;K. Sakuma;H. Naito;T. Yoshioka;S. Powers
蛋白激酶B [PKB，也称为Akt (PKB/Akt)]和钙调磷酸酶（CaN）被认为在骨骼肌细胞内信号整合中发挥重要作用，以应对废弃和增加的肌肉负荷。这些实验研究了废用性肌肉萎缩后恢复过程中PKB/Akt和CaN下游通路信号转导的变化。采用尾悬吊后肢卸料（HLU）法（雄性大鼠）进行10 d的比目鱼肌萎缩。肌肉恢复是通过让动物恢复正常活动3-10天来实现的。从IId/x型和IIb型肌球蛋白重链（MHC）亚型的出现可以看出，HLU导致显著的肌肉萎缩和由慢到快的纤维转变。HLU动物的肌肉质量在重新加载10天后恢复到控制（Con）水平，但肌肉MHC的快速到缓慢的转变是不完整的，正如IId/x型MHC的持续存在所表明的那样。10天的HLU导致肌肉磷酸化PKB/Akt水平显著下降（-43%）。相比之下，在重新加载开始后（3天），HLU动物的肌肉磷酸化PKB/Akt水平高于Con动物（+56%）。在肌肉负荷3天后，HLU动物比目鱼肌磷酸化p70S6K水平显著升高（+26%）。在恢复的第10天，磷酸化的PKB/Akt和磷酸化的p70S6K水平恢复到Con水平。肌肉再负荷10 d后，肌肉CaN水平显著高于Con水平。这些发现与PKB/Akt及其下游介质在肌肉萎缩恢复早期肌肉质量再生中活跃的假设一致。我们的数据支持CaN参与废用肌萎缩恢复后期肌肉重塑的概念。
Protein kinase B [PKB, also known as Akt (PKB/Akt)] and calcineurin (CaN) are postulated to play important roles in integrating intracellular signaling in skeletal muscle in response to disuse and increased muscle loading. These experiments investigated changes in signal transduction of the downstream pathways of PKB/Akt and CaN during recovery following disuse-induced muscle atrophy. A 10-day period of hindlimb unloading (HLU) via tail suspension (male rats) was used to produce soleus muscle atrophy. Muscle recovery was achieved by returning animals to normal ambulation for 3-10 days. HLU resulted in significant muscle atrophy and a slow-to-fast fiber transition as revealed by appearance of type IId/x and IIb myosin heavy chain (MHC) isoforms. Muscle mass in HLU animals recovered to control (Con) levels after 10 days of reloading, but the fast-to-slow shift in muscle MHC was incomplete, as indicated by the continued presence of type IId/x MHC. Ten days of HLU resulted in a significant decrease (-43%) in muscle levels of phosphorylated PKB/Akt. In contrast, muscle levels of phosphorylated PKB/Akt were greater (+56%) in HLU than in Con animals early after the onset of reloading (3 days). Soleus levels of phosphorylated p70S6K were significantly higher (+26%) in HLU animals after 3 days of muscle reloading. Muscle levels of phosphorylated PKB/Akt and phosphorylated p70S6K returned to Con levels by day 10 of recovery. Moreover, muscle CaN levels were significantly higher than Con levels after 10 days of muscle reloading. These findings are consistent with the hypothesis that PKB/Akt and its downstream mediators are active in the regrowth of muscle mass during the early periods of recovery from muscle atrophy. Our data support the concept that CaN is involved in muscle remodeling during the later phases of recovery from disuse muscle atrophy.