Overexpression of inducible 70-kDa heat shock protein in mouse improves structural and functional recovery of skeletal muscles from atrophy

Abstract

Heat shock proteins play a key regulatory role in cellular defense. To investigate the role of the inducible 70-kDa heat shock protein (HSP70) in skeletal muscle atrophy and subsequent recovery, soleus (SOL) and extensor digitorum longus (EDL) muscles from overexpressing HSP70 transgenic mice were immobilized for 7 days and subsequently released from immobilization and evaluated after 7 days. Histological analysis showed that there was a decrease in cross-sectional area of type II myofiber from EDL and types I and II myofiber from SOL muscles at 7-day immobilization in both wild-type and HSP70 mice. At 7-day recovery, EDL and SOL myofibers from HSP70 mice, but not from wild-type mice, recovered their size. Muscle tetanic contraction decreased only in SOL muscles from wild-type mice at both 7-day immobilization and 7-day recovery; however, it was unaltered in the respective groups from HSP70 mice. Although no effect in a fatigue protocol was observed among groups, we noticed a better contractile performance of EDL muscles from overexpressing HSP70 groups as compared to their matched wild-type groups. The number of NCAM positive-satellite cells reduced after immobilization and recovery in both EDL and SOL muscles from wild-type mice, but it was unchanged in the muscles from HSP70 mice. These results suggest that HSP70 improves structural and functional recovery of skeletal muscle after disuse atrophy, and this effect might be associated with preservation of satellite cell amount.

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12skeletal muscle cells

“…HSPs, especially HSP72 and HSP25, are inducible molecular chaperones that are upregulated when cells are exposed to stress (24). The upregulations of HSP72 and HSP25 prevent muscle atrophy, which is caused by disuse and/or immobilization (4,26,38). The transcription of HSPs is mediated by HSF1, which binds to heat shock elements located on HSP genes and induces their expressions (24).…”

“…We previously showed that administration of the HSP inducer geranylgeranylacetone upregulated the expression of inducible 70-kDa HSP (HSP70 and so-called HSP72) and increased protein content in skeletal muscle cells (11). In addition, overexpression of HSP72 in skeletal muscle prevented immobilization-induced atrophy in rat (38) and improved the structural and functional recovery from atrophy of mouse muscle (26). It was also demonstrated that transfection of 27-kDa HSP (HSP27 and so-called HSP25) attenuated the disuse atrophy of rat muscle (4).…”

Frogs and estivation: transcriptional insights into metabolism and cell survival in a natural model of extended muscle disuse

“…Interestingly, there is a decline in expression of various HSPs in atrophied muscles of rats subjected to hindlimb unloading, which is predicted to be associated with impairment of muscle mass recovery (27,45,48). Furthermore, a recent study demonstrated that overexpression of HSP70 in mouse skeletal muscle immobilized for 7 days resulted in improved contractile performance during the recovery period relative to wild-type controls, indicating that HSP70 improved recovery of skeletal muscle following disuse atrophy (34). In C. alboguttata the upregulation of genes involved in refolding and stabilizing proteins in gastrocnemius muscle may be important regulatory mechanisms contributing to the preservation of muscle contractile performance upon emergence from estivation.…”

Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model

“…Second, upregulation of HSP70 was associated with the maintenance of muscle mass and function in the porcine ICU model when animals were only exposed to immobilization, MV, muscle relaxants, and sedation (1,6). It has also been shown that HSP70 directly regulates skeletal muscle atrophy via FOXO signaling (30) and that inducible HSP70 overexpression improves skeletal muscle structure and functional capacity (24).…”