Soleus muscle nascent polypeptide chain elongation slows protein synthesis rate during non-weight-bearing activity.
Soleus muscle nascent polypeptide chain elongation slows protein synthesis rate during non-weight-bearing activity.
复制标题
比目鱼肌新生多肽链伸长会减慢非负重活动期间的蛋白质合成速率。
DOI：
10.1152/ajpcell.1994.267.1.c115
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Thomason,DB
中科院分区：
文献类型：
--
作者：
Ku,Z;Thomason,DB
比目鱼肌的蛋白质合成率在非负重活动期间迅速下降。我们从18小时的非承重比目鱼肌分离的多聚核糖体，以探讨这种现象的机制。多聚核糖体α-肌动蛋白mRNA和18 S rRNA在蔗糖密度梯度上的分布表明，在非承重活动期间，多聚核糖体向更大的尺寸（每个mRNA更多的核糖体）转移。此外，RNA被动员到非承重比目鱼肌的多核糖体池中;这些数据表明蛋白质合成的起始不是速率限制的。我们将这些结果解释为新生多肽链延长的减缓，使得mRNA上的核糖体出现“交通堵塞”，增加了每个mRNA的核糖体数量，同时降低了蛋白质合成速率。为了支持这一假设，用低剂量放线菌酮（一种特异性延伸抑制剂）处理的成肌细胞显示出类似的多核糖体大小变化。蛋白质合成的数值模型进一步表明，在影响蛋白质合成和多核糖体大小方面，延伸比起始和终止更有效。我们的结论是，非承重引起的姿势肌肉蛋白质合成速率的下降最初是由新生多肽链延长的减缓引起的。
Protein synthesis rate of the soleus muscle decreases rapidly during non-weight-bearing activity. We isolated polysomes from 18-h non-weight-bearing soleus muscle to investigate the mechanism of this phenomenon. The distribution of polysomal alpha-actin mRNA and 18S rRNA on sucrose density gradients shows that polysomes shift to larger sizes (more ribosomes per mRNA) during non-weight-bearing activity. Furthermore, RNA is mobilized into the polysome pool of the non-weight-bearing soleus muscle; these data indicate that initiation of protein synthesis is not rate limiting. We explain these results as the slowing of nascent polypeptide chain elongation, such that there is a “traffic jam” of ribosomes on the mRNAs, increasing the number of ribosomes per mRNA while, at the same time, decreasing protein synthesis rate. In support of this hypothesis, myoblasts treated with a low dose of cycloheximide (a specific elongation inhibitor) show a similar shift in polysome size. A numerical model of protein synthesis further shows that elongation is more effective than initiation and termination in affecting protein synthesis and polysome size. We conclude that the non-weight-bearing-induced decrease in postural muscle protein synthesis rate is initially caused by slowing of nascent polypeptide chain elongation.