Early apoptosis signal in hindlimb unloading-induced muscle atrophy

We previously reported that apoptosis occur in skeletal muscle of hindlimb-unloaded rat under at normal or lowtemperature environments, but the apoptosis pathway has not been clarified. In this study, to find out apoptosis pathway and apoptosis-induced factors in apoptotic myofibers, we investigated the reciprocal relationship of the caspase-3 activation to the factors related to mitochondria and other pathways. The following morphological aspects and westernblot analysis results from the caspase-3-activated myofibers in hindlimb-unloading rat under at normal and low-temperature environments. DNA fragmentation, dystrophin breakdown, overexpression of μ-calpain, decrease of cytochrome c, cathepsin-D effusion from lyososome and increase of peroxide lipid were observed, but not caspase-12 overexpression. The expression of eNOS and nNOS have no significant changes compared with intact rats. With other results, it is suggested that apoptosis of hindlimb unloading-induced muscle atrophy might be caused by activation of caspase-3 cascade via lysosome pathway followed by adverse effect of reactive oxygen species.