Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle
Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle
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DOI：
10.1152/japplphysiol.00454.2003
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发表时间：
2004-01-01
影响因子：
3.3
通讯作者：
Booth, FW
中科院分区：
文献类型：
--
作者：
Morris, RT;Spangenburg, EE;Booth, FW
各种细胞信号通路，如磷脂酰肌醇3-激酶、钙调磷酸酶、Janus激酶2/信号转导和转录激活因子3（STAT 3）和丝裂原活化蛋白激酶（MAPK）已被认为在骨骼肌生长中起重要作用。与年轻肌肉相比，老年肌肉在萎缩诱导的刺激后缺乏完全再生其肌肉质量的能力。假设老化比目鱼肌的特定细胞信号传导途径的激活的缺陷和/或延迟限制了生长的潜力。为了测试这一点，将42只30月龄的雄性Fischer 344 x Brown Norway大鼠后肢固定10天，并将它们的肌肉样品与先前报告中分析的3- 4月龄大鼠的肌肉样品进行比较（查尔兹TE，Spangenburg EE，Vyas DR和Booth FW. Am J Physiol Cell Physiol：285：C391 - C398，2003）。10天后，去除固定，并允许大鼠走动一系列天。通过Western印迹法比较10天固定组的磷酸化（phos）和特异性信号蛋白（pan）的总浓度，确定特异性信号通路激活或失活状态的变化。与制动10天组相比，老年大鼠的各种细胞信号及其各自的时间组显示出显著差异。例如，在1）钙调磷酸酶B-pan的第三个恢复日和2）糖原合成酶激酶-3 β-phos、p70 S6激酶（p70（S6 k））- phos和- pan、钙调磷酸酶A-pan、STAT 3-phos和- pan、p44 MAPK- pan和p42 MAPK- pan的第六个恢复日观察到从固定化恢复期间的峰值增加。相比之下，观察到Akt-pan、c-Jun NH 2-末端激酶-phos和p38 MAPK- phos从10天固定值降低至对照水平。此外，所有组中Akt-phos均未发生变化。在后续实验中，将来自本研究和先前研究的肌肉样品（查尔兹TE，斯潘根堡EE，Vyas DR和Booth FW.美国生理学细胞生理学杂志：二百八十五：C391 - C398，2003）一起重新分析，在老年组的比目鱼肌中，由制动-萎缩引起的恢复诱导的p70（S6 k）-phos增加显著减弱。
Various cellular signaling pathways, such as phosphatidylinositol 3-kinase, calcineurin, Janus kinase 2/signal transducer and activator of transcription 3 ( STAT3), and mitogen-activated protein kinase ( MAPK) have been suggested to play an important role in skeletal muscle growth. Old muscle, compared with young muscle, lacks the ability to completely regrow its muscle mass after an atrophy-induced stimulus. it is hypothesized that defects and/or delays in the activation of specific cell signaling pathways of aged soleus muscle limit the potential for growth. To test this, 42 male Fischer 344 x Brown Norway rats, 30 mo old, were hindlimb immobilized for 10 days, and their muscle samples were compared with muscle samples analyzed from 3- to 4-mo-old rats in a previous report (Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391 - C398, 2003). After 10 days, the immobilization was removed and rats were allowed to ambulate for a series of days. Alterations in the activation or deactivation status of specific signaling pathways were determined by comparing the phosphorylation ( phos) and total concentration of specific signaling proteins ( pan) through Western blotting with the 10-day immobilization group. Various cell signals and their respective time groups of the old rats were shown to be significantly different compared with the 10-day immobilization group. For example, peak increases during recovery from the immobilization were observed at 1) the third recovery day for calcineurin B-pan and 2) the sixth recovery day for glycogen synthase kinase-3beta-phos, p70 S6 kinase (p70(S6k)) - phos and - pan, calcineurin A-pan, STAT3-phos and - pan, p44 MAPK- pan, and p42 MAPK- pan. In contrast, Akt- pan, c- Jun NH2-terminal kinase-phos, and p38 MAPK- phos were observed to decrease from 10-day immobilization values to control levels. Also, Akt-phos was unchanged among all groups. In a follow-up experiment in which muscle samples from both the present study and a previous study ( Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391 - C398, 2003) were reanalyzed together, the recovery-induced increase in p70(S6k)-phos from immobilization-atrophy was significantly attenuated in soleus muscles of the old group.