Downhill exercise alters immunoproteasome content in mouse skeletal muscle
Files
Accepted manuscript
Date
2018-07-01
Authors
Baumann, Cory W.
Kwak, Dongmin
Ferrington, Deborah A.
Thompson, LaDora V.
Version
Accepted manuscript
OA Version
Citation
Cory W Baumann, Dongmin Kwak, Deborah A Ferrington, LaDora V Thompson. 2018. "Downhill exercise alters immunoproteasome content in mouse skeletal muscle." Cell Stress & Chaperones, Volume 23, Issue 4, pp. 507 - 517. https://doi.org/10.1007/s12192-017-0857-y
Abstract
Content of the immunoproteasome, the inducible form of the standard proteasome, increases in atrophic muscle suggesting it may be associated with skeletal muscle remodeling. However, it remains unknown if the immunoproteasome responds to stressful situations that do not promote large perturbations in skeletal muscle proteolysis. The purpose of this study was to determine how an acute bout of muscular stress influences immunoproteasome content. To accomplish this, wildtype (WT) and immunoproteasome knockout lmp7-/-/mecl1-/-(L7M1) mice were run downhill on a motorized treadmill. Soleus muscles were excised 1 and 3 days post-exercise and compared to unexercised muscle(control). Ex vivophysiology, histology and biochemical analyses were used to assess the effects of immunoproteasome knockout and unaccustomed exercise. Besides L7M1 muscle being LMP7/MECL1deficient, no other major biochemical, histological or functional differences were observed between the control muscles. In both strains, the downhill run shifted the force-frequency curve to the right and reduced twitch force, however did not alter tetanic force or inflammatory markers. In the days post-exercise, several of the proteasome 's catalytic subunits were upregulated. Specifically, WT muscle increased LMP7 while L7M1 muscle instead increased ≤ 5. These findings indicate that running mice downhill results in subtle contractile characteristics that correspond to skeletal muscle injury, yet does not appear to induce a significant inflammatory response. Interestingly, this minor stress activated the production of specific immunoproteasome subunits; that if knocked out, were replaced by components of the standard proteasome. These data suggest that the immunoproteasome may be involved in maintaining cellular homeostasis.