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核仁以及核糖体蛋白S6和/或热休克蛋白27的磷酸化在肌肉质量调节中的作用

Role(s) of nucleoli and phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass.

作者信息

Kawano F, Matsuoka Y, Oke Y, Higo Y, Terada M, Wang X D, Nakai N, Fukuda H, Imajoh-Ohmi S, Ohira Y

机构信息

Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.

出版信息

Am J Physiol Cell Physiol. 2007 Jul;293(1):C35-44. doi: 10.1152/ajpcell.00297.2006. Epub 2006 Dec 20.

DOI:10.1152/ajpcell.00297.2006
PMID:17182729
Abstract

Effects of 14 days of hindlimb unloading or synergist ablation-related overloading with or without deafferentation on the fiber cross-sectional area, myonuclear number, size, and domain, the number of nucleoli in a single myonucleus, and the levels in the phosphorylation of the ribosomal protein S6 (S6) and 27-kDa heat shock protein (HSP27) were studied in rat soleus. Hypertrophy of fibers (+24%), associated with increased nucleolar number (from 1-2 to 3-5) within a myonucleus and myonuclear domain (+27%) compared with the preexperimental level, was induced by synergist ablation. Such phenomena were associated with increased levels of phosphorylated S6 (+84%) and HSP27 (+28%). Fiber atrophy (-52%), associated with decreased number (-31%) and domain size (-28%) of myonuclei and phosphorylation of S6 (-98%) and HSP27 (-63%), and with increased myonuclear size (+19%) and ubiquitination of myosin heavy chain (+33%, P > 0.05), was observed after unloading, which inhibited the mechanical load. Responses to deafferentation, which inhibited electromyogram level (-47%), were basically similar to those caused by hindlimb unloading, although the magnitudes were minor. The deafferentation-related responses were prevented and nucleolar number was even increased (+18%) by addition of synergist ablation, even though the integrated electromyogram level was still 30% less than controls. It is suggested that the load-dependent maintenance or upregulation of the nucleolar number and/or phosphorylation of S6 and HSP27 plays the important role(s) in the regulation of muscle mass. It was also indicated that such regulation was not necessarily associated with the neural activity.

摘要

研究了14天的后肢卸载或协同肌切除相关的过载(伴或不伴有去传入神经)对大鼠比目鱼肌纤维横截面积、肌核数量、大小和结构域、单个肌核中核仁数量以及核糖体蛋白S6(S6)和27 kDa热休克蛋白(HSP27)磷酸化水平的影响。协同肌切除诱导了纤维肥大(增加24%),与实验前水平相比,肌核内核仁数量增加(从1 - 2个增加到3 - 5个),肌核结构域增加(27%)。这些现象与磷酸化S6水平增加(84%)和HSP27水平增加(28%)相关。卸载后观察到纤维萎缩(减少52%),伴有肌核数量减少(31%)和结构域大小减小(28%),S6和HSP27磷酸化减少(分别为98%和63%),同时肌核大小增加(19%)和肌球蛋白重链泛素化增加(33%,P>0.05),后肢卸载抑制了机械负荷。去传入神经抑制了肌电图水平(47%),其反应与后肢卸载引起的反应基本相似,尽管程度较小。即使综合肌电图水平仍比对照组低30%,通过添加协同肌切除可防止去传入神经相关反应,且核仁数量甚至增加(18%)。提示核仁数量和/或S6及HSP27磷酸化的负荷依赖性维持或上调在肌肉质量调节中起重要作用。还表明这种调节不一定与神经活动相关。

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