Heat Shock Factor Activation in Skeletal Muscle Following Lengthening Contractions

Abstract

Heat shock proteins (HSPs) are integral for the maintenance of proteostasis and allowing cells to cope with episodes of stress. HSPs are regulated by transcription factors known as heat shock transcription factors (HSFs). Given that when skeletal muscles are subjected to lengthening contractions (LCs) both muscle damage and HSPs are increased, it was of interest to investigate the mechanism of the LC‐induced increase in HSPs and assess the role of HSFs in this process. Thus, the purpose of this study was to determine if HSF activation (HSF trimerization and DNA binding) is elevated in rat skeletal muscle following exposure to 60 LCs. To do this, male sprague‐dawley rats were anaesthetized and one tibialis anterior (TA) muscle was subjected to 60 LCs (3 sets of 20 LCs with 5 minutes rest between sets) and removed at 0, 1, 3, or 24 hours after LCs, while the non‐stimulated contralateral TA served as a control. Hsp72 and Hsp25 content, HSF activation, muscle damage, and muscle glycogen content were assessed at various time points. Following 60 LCs, electrophoretic shift assay showed a transient increase in HSF activation (0–3 hours) that was followed by a significant (p<0.001) increase in Hsp72 (3.4±0.21 fold) and Hsp25 (3.2±1.2 fold) content 24 hours later as assessed by western blotting. Histological assessment of the TA muscle revealed evidence of muscle damage (measured as necrotic fibers and inflammatory infiltrates) and glycogen depletion. Taken together, the results suggest LCs induce structural and metabolic stress that results in muscle damage, increased HSF activation and the accumulation of Hsp72 and Hsp25.Support or Funding InformationNo external funding