Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.
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DOI:
10.1371/journal.pone.0147284
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Ishii N
Ishii N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nakada S;Ogasawara R;Kawada S;Maekawa T;Ishii N

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施加于骨骼肌的外部负荷会导致蛋白质转换率增加,从而导致肌肉肥大。虽然一些研究表明翻译能力和效率的增加参与了这一过程,但这两个因素如何与肌肉肥大的程度相关仍不清楚。本研究旨在阐明翻译的能力和效率在肌肉肥大中所起的作用。我们使用了一种改进的协同消融,其中代偿性肥厚的程度可以通过部分切除协同肌肉来控制。将雄性大鼠分为4组,分别采用4种协同消融方法造成一侧足底肌弱负荷(WK)、中度负荷(MO)、中度负荷(MI)和重度负荷(ST)。术后14天,WK组、MO组、MI组和ST组的足底肌重分别增加8%、22%、32%和45%。术后5天,18+28S rRNA含量(翻译能力的一个指标)随着超负荷的增加而增加,与非超负荷肌肉(NL)相比,WK组分别增加1.8倍(MO)、2.2倍(MI)和2.5倍(ST)。RRNA含量与术后14天测得的相对肌重有很强的相关性(r=0.98)。P70S6K的磷酸化形式(翻译效率的正向调节因子)在MO组显著增加,但随着超负荷的进一步增加(WK组相对于NL分别增加22.6倍(MO)、17.4倍(MI)和18.2倍(ST)),未观察到进一步增加。这些结果表明,超负荷早期核糖体生物合成的增加强烈地依赖于超负荷的量,并且可能在增加进一步增加肌肉大小的翻译能力方面发挥重要作用。
External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK), moderate (MO), middle (MI), and strong (ST) overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity) increased with increasing overload, with increases of 1.8-fold (MO), 2.2-fold (MI), and 2.5-fold (ST), respectively, relative to non-overloaded muscle (NL) in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98). The phosphorylated form of p70S6K (a positive regulator of translational efficiency) showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO), 17.4-fold (MI), and 18.2-fold (ST), respectively, relative to NL in the WK group). These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size.