Menon V, Yang J, Ku Z, Thomason D B
Department of Physiology and Biophysics, University of Tennessee Health Science Center, Memphis 38163, USA.
Am J Physiol. 1995 Jun;268(6 Pt 1):C1375-80. doi: 10.1152/ajpcell.1995.268.6.C1375.
This study examines the mechanism of the rapid decrease in cardiac muscle protein synthesis during rodent hindlimb non-weight bearing. Polysomes isolated from rat hearts 8 h after suspension show less RNA in the polysome pool and a shift in polysome size toward fewer ribosomes per mRNA; 18 h after suspension, the size shift persists, but the amount of RNA in the polysome pool returns to control values. These data are consistent with a decrease in the rate of initiation of protein synthesis. At both 8 and 12 h of suspension, the cardiac polysomes show a 78 and 93% increase association with the nascent polypeptide chaperone protein 70-kDa heat-shock cognate/heat-shock protein (HSC/HSP-70), respectively, that persists after 7 days of non-weight bearing. Because the dissociation of HSC/HSP-70 from unfolded protein can be modulated by ATP, we measured the adenosine nucleotide pools and found a 53% decrease in ATP levels after 18 h of suspension. We propose a mechanism in which a shift of HSC/HSP-70 to the nascent polypeptide indirectly inhibits protein synthesis initiation.
本研究探讨了啮齿动物后肢不负重期间心肌蛋白合成快速下降的机制。在悬吊8小时后从大鼠心脏分离的多核糖体显示，多核糖体池中的RNA减少，且多核糖体大小发生变化，每个mRNA上的核糖体数量减少；悬吊18小时后，大小变化持续存在，但多核糖体池中的RNA量恢复到对照值。这些数据与蛋白质合成起始速率的降低一致。在悬吊8小时和12小时时，心脏多核糖体与新生多肽伴侣蛋白70 kDa热休克同源蛋白/热休克蛋白（HSC/HSP - 70）的结合分别增加了78%和93%，这种增加在不负重7天后仍然存在。由于HSC/HSP - 70从未折叠蛋白上的解离可由ATP调节，我们测量了腺苷核苷酸池，发现悬吊18小时后ATP水平下降了53%。我们提出了一种机制，即HSC/HSP - 70向新生多肽的转移间接抑制了蛋白质合成起始。
