MetaTOC stay on top of your field, easily

Activation of alternative NF-{kappa}B signaling during recovery of disuse-induced loss of muscle oxidative phenotype

, , , ,

AJP Endocrinology and Metabolism

Published online on

Abstract

BACKGROUND: Physical inactivity-induced loss of skeletal muscle oxidative phenotype (OXPHEN), often observed in chronic disease, adversely affects physical functioning and quality of life. Potential therapeutic targets remain to be identified as the molecular mechanisms involved in reloading-induced recovery of muscle OXPHEN remain incompletely understood. We hypothesized a role for alternative NF-B, as a recently identified positive regulator of muscle OXPHEN, in reloading-induced alterations in muscle OXPHEN. METHODS: Markers and regulators (including alternative NF-B signaling) of muscle OXPHEN were investigated in gastrocnemius muscle of mice subjected to a hind limb suspension/reloading (HLS/RL) protocol. RESULTS: Expression levels of oxidative phosphorylation (OXPHOS) sub-units and slow myosin heavy chain (MyHC) isoforms I and IIA increased rapidly upon RL. After an initial decrease upon HLS, mRNA levels of peroxisome proliferator-activated receptor (PPAR) gamma co-activator (PGC) molecules PGC-1α and PGC-1β and mRNA levels of mitochondrial transcription factor A (Tfam) and estrogen-related receptor α (ERR-α) increased upon RL. PPAR-, nuclear respiratory factor 1 (NRF-1), NRF-2α and sirtuin 1 mRNA levels increased during RL although expression levels were unaltered upon HLS. In addition, both Tfam and NRF-1 protein levels increased significantly during the RL period. Moreover, upon RL, IKK-α mRNA and protein levels increased and phosphorylation of P100 and subsequent processing to P52 was elevated, reflecting alternative NF-B activation. CONCLUSION: RL-induced recovery of muscle OXPHEN is associated with activation of alternative NF-B signaling.