Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload

Knowledge of the molecular mechanisms by which skeletal muscle hypertrophie s in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle h ypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity du ring the first 24 h of muscle overload was determined in the rat slow-twitc h soleus and fast-twitch plantaris muscles after ablation of the gastrocnem ius muscle. p38 alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphoryl ation were transiently increased by overload, returning to the levels of sh am-operated controls by 24 h. PI3-kinase activity was increased by muscle o verload only at 12 h of overload and only in the plantaris muscle. In summa ry, sustained elevation of p38a MAPK phosphorylation occurred early in resp onse to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle ove rload.