Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading.
Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading.
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DOI：
10.1002/jcsm.12636
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Cameron-Smith D
中科院分区：
文献类型：
--
作者：
Figueiredo VC;D'Souza RF;Van Pelt DW;Lawrence MM;Zeng N;Markworth JF;Poppitt SD;Miller BF;Mitchell CJ;McCarthy JJ;Dupont-Versteegden EE;Cameron-Smith D
翻译能力（即核糖体质量）是蛋白质合成的关键决定因素，并且与骨骼肌肥大有关。翻译能力在肌肉萎缩和废用再生中的作用在很大程度上尚不清楚。因此，我们研究了肌肉废用和重新加载对中年男性（研究 1）和大鼠（研究 2）翻译能力的影响。在研究 1 中，28 名男性参与者（年龄 50.03 ± 3.54 岁）接受了 2 周的膝盖固定，然后是 2 周的卧床恢复和另外 2 周的阻力训练。获得肌肉活检以测量总 RNA 和前核糖体 (r)RNA 表达，并通过外周定量计算机断层扫描确定股外侧肌横截面积 (CSA)。在研究 2 中，雄性大鼠接受后肢悬吊 (HS) 24 小时（HS 24 小时，n = 4）或 7 天（HS 7 天，n = 5），HS 7 天，然后重新加载 7 天（Rel，n = 5）或保持动态负重（WB，n = 5）对照。在整个研究过程中，大鼠接受氧化氘以确定 RNA 合成和降解，并评估 mTORC1 信号通路。两周的固定降低了男性的总 RNA 浓度 (20%) 和 CSA (4%)（均 P ≤ 0.05）。动态恢复使总 RNA 浓度恢复至基线水平，并部分恢复肌肉 CSA。阻力训练后总 RNA 浓度和 47S pre-rRNA 表达增加至基础水平以上 (P ≤ 0.05)。在大鼠中，与 WB 相比，HS 7d 中比目鱼肌和跖肌的 RNA 合成降低了 30%，而降解则增加了约 400%（P ≤ 0.05）。与 WB 相比，HS 中的 mTORC1 信号传导较低，47S pre-rRNA 也是如此 (P ≤ 0.05)。重新加载后，上述参数恢复至 WB 水平，同时 RNA 降解受到抑制 (P ≤ 0.05)。肌肉废弃和重新加载后 RNA 浓度的变化与核糖体生物合成和降解的变化相关，表明这两个过程都是翻译能力的重要决定因素。临床前数据有助于解释人类肌肉固定后翻译能力的降低，并证明核糖体生物发生和降解可能是在废弃期间维持肌肉质量的有价值的治疗靶点。
Translational capacity (i.e. ribosomal mass) is a key determinant of protein synthesis and has been associated with skeletal muscle hypertrophy. The role of translational capacity in muscle atrophy and regrowth from disuse is largely unknown. Therefore, we investigated the effect of muscle disuse and reloading on translational capacity in middle‐aged men (Study 1) and in rats (Study 2). In Study 1, 28 male participants (age 50.03 ± 3.54 years) underwent 2 weeks of knee immobilization followed by 2 weeks of ambulatory recovery and a further 2 weeks of resistance training. Muscle biopsies were obtained for measurement of total RNA and pre‐ribosomal (r)RNA expression, and vastus lateralis cross‐sectional area (CSA) was determined via peripheral quantitative computed tomography. In Study 2, male rats underwent hindlimb suspension (HS) for either 24 h (HS 24 h, n = 4) or 7 days (HS 7d, n = 5), HS for 7 days followed by 7 days of reloading (Rel, n = 5) or remained as ambulatory weight bearing (WB, n = 5) controls. Rats received deuterium oxide throughout the study to determine RNA synthesis and degradation, and mTORC1 signalling pathway was assessed. Two weeks of immobilization reduced total RNA concentration (20%) and CSA (4%) in men (both P ≤ 0.05). Ambulatory recovery restored total RNA concentration to baseline levels and partially restored muscle CSA. Total RNA concentration and 47S pre‐rRNA expression increased above basal levels after resistance training (P ≤ 0.05). In rats, RNA synthesis was 30% lower while degradation was ~400% higher in HS 7d in soleus and plantaris muscles compared with WB (P ≤ 0.05). mTORC1 signalling was lower in HS compared with WB as was 47S pre‐rRNA (P ≤ 0.05). With reloading, the aforementioned parameters were restored to WB levels while RNA degradation was suppressed (P ≤ 0.05). Changes in RNA concentration following muscle disuse and reloading were associated with changes in ribosome biogenesis and degradation, indicating that both processes are important determinants of translational capacity. The pre‐clinical data help explain the reduced translational capacity after muscle immobilization in humans and demonstrate that ribosome biogenesis and degradation might be valuable therapeutic targets to maintain muscle mass during disuse.
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DOI：
10.1002/jcsm.12266
发表时间：
2018-04
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Connolly M;Paul R;Farre-Garros R;Natanek SA;Bloch S;Lee J;Lorenzo JP;Patel H;Cooper C;Sayer AA;Wort SJ;Griffiths M;Polkey MI;Kemp PR
通讯作者：
Kemp PR
DOI：
10.1016/j.biocel.2013.06.011
发表时间：
2013-10
影响因子：
4
作者：
Bodine, Sue C.
通讯作者：
Bodine, Sue C.
影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
5.5
作者：
GOLDSPINK, DF
通讯作者：
GOLDSPINK, DF
影响因子：
5.5
作者：
Glover, Elisa I.;Phillips, Stuart M.;Rennie, Michael J.
通讯作者：
Rennie, Michael J.