Morris R Tyler, Spangenburg Espen E, Booth Frank W
Department Medical Pharmacology and physiology, University of Missouri, Columbia, MO 65211, USA.
J Appl Physiol (1985). 2004 Jan;96(1):398-404. doi: 10.1152/japplphysiol.00454.2003. Epub 2003 Sep 26.
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 (p70S6k) -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, Aktphos 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 p70S6k-phos from immobilization-atrophy was significantly attenuated in soleus muscles of the old group.
多种细胞信号通路，如磷脂酰肌醇3激酶、钙调神经磷酸酶、Janus激酶2/信号转导及转录激活因子3（STAT3）和丝裂原活化蛋白激酶（MAPK），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刺激后缺乏完全恢复其肌肉质量的能力。据推测，老年比目鱼肌特定细胞信号通路激活的缺陷和/或延迟限制了其生长潜力。为了验证这一点，将42只30月龄的雄性Fischer 344×Brown Norway大鼠后肢固定10天，并将其肌肉样本与之前一份报告（Childs TE、Spangenburg EE、Vyas DR和Booth FW。《美国生理学杂志：细胞生理学》：285：C391 - C398，2003）中3至4月龄大鼠的肌肉样本进行比较。10天后，解除固定，让大鼠活动一系列天数。通过蛋白质免疫印迹法比较10天固定组特定信号蛋白的磷酸化（phos）和总浓度（pan），以确定特定信号通路激活或失活状态的变化。结果显示，与10天固定组相比，老年大鼠的各种细胞信号及其各自的时间组存在显著差异。例如，在固定恢复过程中，峰值增加出现在：1）钙调神经磷酸酶B - pan在恢复第3天；2）糖原合酶激酶 - 3β - phos、p70核糖体蛋白S6激酶（p70S6k） - phos和 - pan、钙调神经磷酸酶A - pan、STAT3 - phos和 - pan、p44 MAPK - pan以及p42 MAPK - pan在恢复第6天。相反，Akt - pan以及c - Jun氨基末端激酶 - phos和p38 MAPK - phos从10天固定值降至对照水平。此外，Aktphos在所有组中均无变化。在一项后续实验中，将本研究和之前一项研究（Childs TE、Spangenburg EE、Vyas DR和Booth FW。《美国生理学杂志：细胞生理学》：285：C391 - C398，2003）的肌肉样本一起重新分析，发现老年组比目鱼肌中固定萎缩后恢复诱导的p70S6k - phos增加显著减弱。
