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1 Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA
2 Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA
3 Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA; Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA; Dalton Cardiovascular Institute, University of Missouri, Columbia, MO, USA
* To whom correspondence should be addressed. E-mail: boothf{at}missouri.edu.
Various cellular signaling pathways, such as PI3-K, calcineurin, JAK2-STAT3, and MAPK have been suggested to play an important role in skeletal muscle growth. Old muscle, as compared to young muscle, lacks the ability to completely regrow its muscle mass after an atrophy-induced stimulus. Thus, it is hypothesized that defects and/or delays in the activation of specific cell signaling pathways of aged soleus muscle limits the potential for growth. To test this, 42 male Fischer 344xBN rats, 30 month old, were hindlimb immobilized for 10 days and compared to muscle samples analyzed from 3-4-mo-old rats in a previous report. 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 to the 10 day immobilization group. Various cell signals and their respective time groups of the old rats were shown to be significantly different when compared to the 10-day immobilization group. For example, peak increases during recovery from the immobilization were observed at: 1) the 3rd recovery day for calcineurin-B-pan, 2) and the 6th recovery day for: GSK-3
-phos, p70S6K-phos and pan, calcineurin-A-pan, STAT-3-phos and pan, MAPK44-pan, and MAPK42-pan. In contrast, Akt-pan, JNK-phos, and p38MAPK-phos were observed to decrease from 10-day immobilization values to control levels. Also, Akt phosphorylation was unchanged among all groups. In a follow-up experiment in which muscle samples from both the current study and a previous study were re-analyzed together, the recovery-induced increase in p70S6K-phos from immobilization-atrophy was significantly attenuated in soleus muscles of the old group.
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