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

Abstract

[Purpose] The purpose of this study was to elucidate the cathepsin-D involvement in signaling pathways for the survival and apoptosis of myofibers in rats with hindlimb-unloading in a low-temperature environment. [Subjects and Methods] Wistar rats were divided into two groups: a control group and a group that underwent hindlimb unloading in a low-temperature environment to induce muscle apoptosis. Cathepsin-D localization in the soleus and extensor digitorum longus muscles, along with the expression of cathepsin-D in apoptotic myofibers, was examined. Expression of the active and inactive forms of cathepsin-D was also analyzed. [Results] Cathepsin-D was mainly expressed in type I myofibers and was observed to have punctate patterns in the control group. In the hindlimb unloading in a low-temperature environment group, the type I myofiber composition ratio decreased, and caspase-3 activation and TUNEL-positive apoptotic myofibers were observed. In caspase-3-activated myofibers, cathepsin-D overexpression and leakage of it into the cytoplasm were observed. In the hindlimb unloading in a low-temperature environment group, the amount of inactive cathepsin-D decreased, whereas that of the active form increased. [Conclusion] Cathepsin-D was deduced to be indicative of a myofiber-type classification and a factor related to myofiber type maintenance. In addition, cathepsin-D leakage into the cytoplasm was appeared to be involved in caspase-3 activation in the hindlimb unloading in a low-temperature environment group.

Skeletal Muscle Myofibrillar Protein Abundance Is Higher in Resistance-Trained Men, and Aging in the Absence of Training May Have an Opposite Effect

“…These pathways collectively suggest that aspects of oxidative metabolism are greater in muscle from older participants, and this age-related phenomenon has been previously reported [32]. It is also interesting to note that cathepsin D (CTSD), which is involved with lysosomal proteolysis [35], was greatest in older participants, and that proteins involved with other proteolysis pathways were not affected; specifically proteins involved with the ubiquitin proteasome (UBE2V2, USP14, UBE2L3, USP5, UBE2N, PSMA1, PSMA3, PSMA6, PSMA7, PSMB1, PSMB4, PSMB7, PSMD2, PSME1) or calpain pathways (CAPN1, CAPN2, CAPN3) were not differently expressed between age groups. These data agree with previous reports which showed that cathepsin D is upregulated in older human [36] and rodent skeletal muscle [37], and this may be an age-related atrophy target that should be further interrogated.…”

Identification of new biomarkers for sarcopenia and characterization of cathepsin D biomarker

“…Cathepsins in general are involved in lysosomal death pathways, autophagy, and aging mostly in neurodegenerative disorders 33 . Cathepsin B, for example, is involved in myoblast differentiation, 34 and cathepsin D is present in atrophied muscles and apoptotic myofibers 35 . In summary, from what is already known, these two proteins could be involved in muscle energy metabolism and apoptosis of myoblasts.…”

Quantitative analysis of approximate shapes in a myofiber cross-section and their relationship with myofiber cross-sectional area

“…There are several types of myofibers in the soleus muscle. Type I comprise 90% of the myofibers in the muscle tissues of humans 11 ) , approximately 80% in that of 10-week-old male rats 12 ) , and approximately 90% in that of 12-week-old male rats 13 ) . As the samples used in this study were taken from the soleus muscle of 11-week-old rats, the majority of measured myofibers were likely type I myofibers, and the approximate shapes of the MFCS obtained likely reflected the form of type I myofibers.…”