Expression of endoplasmic reticulum stress proteins during skeletal muscle disuse atrophy

Disuse atrophy of skeletalmuscle leads to an upregulation of genes encoding sarcoplasmicreticulum (SR) calcium-handling proteins. Because many of theproteins that are induced with endoplasmic reticulum (ER) stress are ERcalcium-handling proteins, we sought to determine whether soleus muscleatrophy was associated with a prototypical ER stress response. Sevendays of rat hindlimb unloading did not alter expression of ubiquitousER stress proteins such as Grp78, calreticulin, and CHOP/GADD-153, norother proteins that have been shown to be activated by ER stressorssuch as vinculin, the type I D-myo-inositol1,4,5-trisphosphate receptor, or protein kinase R, a eukaryoticinitiation factor 2 kinase. On the other hand, expression of hemeoxygenase-1 (HO-1), an antioxidant ER stress protein, was significantlyincreased 2.2-fold. In addition, unloading led to an increase incalsequestrin, the muscle-specific SR calcium-binding protein, at boththe mRNA (68%) and protein (24%) levels. Although disuse atrophy isassociated with a significant remodeling of muscle-specific proteinscontrolling SR calcium flux, it is not characterized by a prototypicalER stress response. However, the upregulation of HO-1 may indicate ERadaptation to oxidative stress during muscle unloading.