Cyclic-stretch induces the apoptosis of myoblast by activation of Caspase-3 protease in a magnitude-dependent manner

Abstract

Although many studies have been performed investigating the effects of mechanical stress on the generation and differentiation of myoblasts, little is known about the effects of different magnitudes of mechanical stretch on apoptosis in these cells. The aim of this study was to investigate the effects of different magnitudes of cyclic stretch on apoptosis levels in myoblasts and to investigate the possible mechanisms involved. Myoblasts were cultured on flexible membranes and subjected to cyclic strain stress in a magnitude-dependent manner (6%, 12% or 20% surface elongation). Apoptosis rates were evaluated using flow cytometry, transmission electron microscopy, and caspase assays. Fas/FasL expression was determined by Western blot. The application of different magnitudes of cyclic-stretch-induced a magnitude-dependent increase in apoptosis and caspase-3 activity in cultured myoblasts. Furthermore, inhibition of caspase-3 prevented stretch-induced apoptosis in myoblasts but did not change Fas and FasL protein levels. These data indicate that cyclic stretch induces a magnitude- and caspase-3-dependent increase of apoptosis in cultured myoblasts in vitro. Mechanical forces induced activation of caspase-3 through signalling pathways independent of the Fas/FasL system. These results suggest the existence of a novel mechanism for the regulation of myoblast apoptosis by cyclic stretch.