Ku Z, Thomason D B
Department of Physiology and Biophysics, University of Tennessee College of Medicine, Memphis 38163.
Am J Physiol. 1994 Jul;267(1 Pt 1):C115-26. doi: 10.1152/ajpcell.1994.267.1.C115.
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.
比目鱼肌的蛋白质合成速率在非负重活动期间迅速下降。我们从18小时非负重的比目鱼肌中分离出多核糖体，以研究这种现象的机制。多核糖体α-肌动蛋白mRNA和18S rRNA在蔗糖密度梯度上的分布表明，在非负重活动期间，多核糖体向更大尺寸转移（每个mRNA上的核糖体更多）。此外，RNA被动员到非负重比目鱼肌的多核糖体库中；这些数据表明蛋白质合成的起始不是限速步骤。我们将这些结果解释为新生多肽链延伸的减慢，使得mRNA上存在核糖体的“交通堵塞”，增加了每个mRNA上的核糖体数量，同时降低了蛋白质合成速率。为支持这一假设，用低剂量环己酰亚胺（一种特异性延伸抑制剂）处理的成肌细胞显示出多核糖体大小的类似变化。蛋白质合成的数值模型进一步表明，延伸在影响蛋白质合成和多核糖体大小方面比起始和终止更有效。我们得出结论，非负重引起的姿势肌蛋白质合成速率下降最初是由新生多肽链延伸减慢引起的。
