Endoplasmic reticulum stress increases myofiber formation in vitro

Myoblast differentiation involves myoblast fusion followed by myofiber formation. We recently demonstrated that endoplasmic reticulum (ER) stress signaling occurs during myoblast differentiation in vivo. This signaling results in apoptosis in a subpopulation of myoblasts. In a cell culture model of myogenesis, inhibition of ER stress signaling blocked apoptosis and myoblast differentiation. To further examine the role of ER stress during myogenesis, we exposed cultured myoblasts to ER stress inducers during the transition from proliferation to differentiation. The stress inducers tunicamycin (an inhibitor of N-glycosylation in the ER) and thapsigargin (an inhibitor of ER-specific calcium ATPase) were used at doses that induce 40–50% apoptosis in myoblast cultures. Increased ER stress enhanced differentiation-associated apoptosis of myoblasts. It is likely that apoptosis induced by ER stress selectively eliminates vulnerable cells. We found that the surviving myoblast cells were even more resistant to apop...