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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.

最近有报道认为Akt/mTOR/p70^<S6K>/S6和钙调神经磷酸酶（CaN）在骨骼肌响应废用和增加的肌肉负荷的细胞内信号整合中起重要作用。这些实验研究了在固定诱导的肌肉萎缩后恢复期，Akt/mTOR/p70^ /S6和CaN下游通路的信号转导中与年龄相关的差异<S6K>。用石膏模型固定幼年（10周）、成年（1岁）和老年（2岁）的一侧后肢肌肉，使其处于跖屈位10天。石膏模型取出后0、7、-15天，取出萎缩侧和对侧跖肌，制动后所有实验动物均出现明显的肌萎缩。10天恢复期后，幼龄动物的肌肉质量恢复至约90%，但成年和老年动物的肌肉质量未恢复。与对照组相比，年轻大鼠萎缩肌肉中磷酸化Akt、磷酸化mTOR和磷酸化p70的表达<S6K>在所有恢复期均显著升高，在恢复15天观察到最大变化，但在成年和老年动物中没有观察到。在恢复7天和15天后，年轻大鼠的磷酸化56的肌肉水平较高。在成年大鼠中观察到类似的趋势，但在老年大鼠中没有观察到。在恢复期和实验组中，萎缩肌肉中磷酸化eIF 4 E和钙调神经磷酸酶的表达无变化。在恢复后7天和15天，年轻大鼠的磷酸化eIF 4G肌肉水平较高，但成年和老年大鼠则不然。这些结果表明，Akt/mTOR信号通路的激活参与蛋白质合成在恢复过程中萎缩的跖肌不同的年龄。