Age-related differences in signal transduction during recovery in atrophied plantaris muscle induced by immobilization

固定引起的萎缩跖肌恢复过程中信号转导的年龄相关差异

基本信息

批准号：
17500428
负责人：
SUGIURA Takao
金额：
$ 2.52万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17500428/
关键词：
muscle atrophy restoration signal ransduction aging

项目摘要

It has been recently reported that Akt/mTOR/p70^<S6K>/S6 and calcineurin (CaN) are both postulated to play important roles in integrating intracellular signaling in skeletal muscle in response to both disuse and increased muscle loading. These experiments investigated the age-related differences in signal transduction of the downstream pathways of both Akt/mTOR/p70^<S6K>/S6 and CaN during a period of recovery following immobilization-induced muscle atrophy. The hindlimb muscles of one leg in young (10 weeks), adult (1 year) and old (2 years) were immobilized in plantar flexion position using a plaster cast for 10 days. At 0,7 and-15 days after the removal of plaster cast, both the atrophic and the contralateral plantaris muscles were removed.Immobilization resulted in significant muscle atrophy in all experimntal animals. Muscle mass in young animal recovered up to -90% following 10-days of recovery period, but not in adult and old animals. The expressions of phospho-Akt, phospho-mTOR and phospho- p70^<S6K> in atrophied muscles from young rats were significantly higher in all of recovery period compared with control muscles, with the greatest changes seen in recovery day 15, but not in adult and old animals. Muscle levels of phosphorylated 56 in young rats were higher following 7-and 15 days of recovery. A similar tendency was observed in adult rats, but not in old rats. The expressions of phospho-eIF4E and calcineurin in atrophied muscles were unchanged in all of recovery period and experimental groups. Muscle levels of phosphorylated eIF4G in young rats were higher following 7-and 15 days of recovery, but not in adult and old rats. These results show that the activation of Akt/mTOR signaling pathways involved in the protein synthesis during recovery in atrophied plantaris muscle differ with age.

最近有报道称，Akt/mTOR/p70^<S6K>/S6 和钙调神经磷酸酶 (CaN) 均被认为在骨骼肌中整合细胞内信号传导以响应废用和肌肉负荷增加方面发挥重要作用。这些实验研究了在固定诱导的肌肉萎缩后的恢复期间，Akt/mTOR/p70^<S6K>/S6 和 CaN 下游途径的信号转导与年龄相关的差异。使用石膏将幼年（10周）、成年（1岁）和老年（2岁）的一条腿后肢肌肉以跖屈位置固定10天。在去除石膏后0.7天和15天，萎缩的足底肌和对侧跖肌均被去除。固定导致所有实验动物出现显着的肌肉萎缩。幼年动物的肌肉质量在 10 天的恢复期后恢复至 -90%，但成年和老年动物则不然。幼年大鼠萎缩肌肉中磷酸化Akt、磷酸化mTOR和磷酸化p70^<S6K>的表达在整个恢复期均显着高于对照肌肉，其中恢复第15天变化最大，但恢复第15天变化最大。成年和老年动物。恢复 7 天和 15 天后，年轻大鼠的肌肉磷酸化 56 水平较高。在成年大鼠中观察到类似的趋势，但在老年大鼠中则没有。萎缩肌肉中磷酸化eIF4E和钙调磷酸酶的表达在所有恢复期和实验组中均无变化。恢复 7 天和 15 天后，年轻大鼠的肌肉磷酸化 eIF4G 水平较高，但成年大鼠和老年大鼠则不然。这些结果表明，萎缩的跖肌恢复过程中参与蛋白质合成的 Akt/mTOR 信号通路的激活随年龄而变化。