Protein Kinase D1 Inhibits AMP-Activated Protein Kinase Activity in the Rat Postural Muscle during the Initial Stage of Mechanical Unloading

It is well established that the early stage of mechanical unloading in both humans and animals is characterized by a decline in the activity of the key cellular energy sensor, AMP-activated protein kinase (AMPK). This decline triggers signaling pathways that drive myosin phenotype remodeling and muscle atrophy. However, the molecular mechanisms underlying the reduction in AMPK activity under these conditions remain poorly understood. We hypothesized that elevated activity of protein kinase D1 (PKD1) could contribute to the decline in AMPK activity during the initial stage of rat hindlimb unloading. The present study demonstrates that the suppression of upregulated PKD1 activity via a specific inhibitor (CRT0066101) during 24-hour unloading results in the restoration of AMPK activity in the rat soleus muscle. Thus, we have shown for the first time the contribution of PKD1 to the regulation of AMPK activity in the mammalian postural muscle during the initial stage of hindlimb unloading.