Muscle‐specific Keap1 deletion enhances force production but does not prevent inactivity‐induced muscle atrophy in mice

• DOI: 10.1096/fj.202402810r
• Publication Date: 2025-03-14T15:48:31Z
• Authors: Edwin R. Miranda; Justin L. Shahtout; Shinya Watanabe; Norah Milam; Takuya Karasawa; Subhasmita Rout; Donald L. Atkinson; William L. Holland; Micah J. Drummond; Katsuhiko Funai
• Keywords: Muscle Atrophy; KEAP1; Muscle weakness; Myofibril

Immobilization-associated muscle atrophy and weakness appear to be driven in part by oxidative stress. Nuclear Factor Erythroid 2-Related 2 (NRF2) is a critical redox rheostat that regulates stress responses, its deletion known accelerate during aging (sarcopenia) or denervation. Conversely, pharmacologic activation of NRF2 extends mouse lifespan attenuates sarcopenia. Similarly, Kelch-like ECH-associated Protein 1 (Keap1), negative regulator NRF2, enhances exercise capacity. The purpose this study was determine whether muscle-specific Keap1 sufficient prevent mice following 7 days hindlimb unloading (HU). To test hypothesis, control (Ctrl) tamoxifen-inducible, knockout (mKO) were subjected either normal housing (Sham) HU for days. Activation confirmed increased mRNA targets thioredoxin (Txn1) NAD(P)H quinone dehydrogenase (NQO1) mKO mice. had an effect increase force-generating capacity at baseline. However, masses, cross-sectional area, ex vivo force not different between Ctrl In addition, 4-hydroxynonenal-modified proteins protein carbonyls unaffected deletion. These data suggest improves production ambulatory conditions but HU.