Alteration of cathepsin-D expression in atrophied muscles and apoptotic myofibers by hindlimb unloading in a low-temperature environment

[Purpose] The purpose of this study was to elucidate the cathepsin-D involvement insignaling pathways for the survival and apoptosis of myofibers in rats withhindlimb-unloading in a low-temperature environment. [Subjects and Methods] Wistar ratswere divided into two groups: a control group and a group that underwent hindlimbunloading in a low-temperature environment to induce muscle apoptosis. Cathepsin-Dlocalization in the soleus and extensor digitorum longus muscles, along with theexpression of cathepsin-D in apoptotic myofibers, was examined. Expression of the activeand inactive forms of cathepsin-D was also analyzed. [Results] Cathepsin-D was mainlyexpressed in type I myofibers and was observed to have punctate patterns in the controlgroup. In the hindlimb unloading in a low-temperature environment group, the type Imyofiber composition ratio decreased, and caspase-3 activation and TUNEL-positiveapoptotic myofibers were observed. In caspase-3-activated myofibers, cathepsin-Doverexpression and leakage of it into the cytoplasm were observed. In the hindlimbunloading in a low-temperature environment group, the amount of inactive cathepsin-Ddecreased, whereas that of the active form increased. [Conclusion] Cathepsin-D was deducedto be indicative of a myofiber-type classification and a factor related to myofiber typemaintenance. In addition, cathepsin-D leakage into the cytoplasm was appeared to beinvolved in caspase-3 activation in the hindlimb unloading in a low-temperatureenvironment group.Key words: Cathepsin-D, Apoptosis, Muscle fiber type