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Recovery of disuse‐induced loss of muscle oxidative phenotype is associated with alternative NF‐κB signaling during reloading
Author(s) -
Remels Alexander,
Pansters Nicky,
Gosker Harry,
Schols Annemie,
Langen Ramon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.939.17
Subject(s) - tfam , skeletal muscle , oxidative phosphorylation , sirtuin , mitochondrial biogenesis , transcription factor , phosphorylation , sirtuin 1 , microbiology and biotechnology , peroxisome proliferator activated receptor , biology , chemistry , medicine , endocrinology , mitochondrion , receptor , biochemistry , downregulation and upregulation , acetylation , gene
BACKGROUND Loss of skeletal muscle oxidative phenotype (OXPHEN) upon mechanical unloading is evident. However, the molecular mechanisms involved in reloading‐induced recovery of muscle OXPHEN remain unclear. Interestingly, the alternative NF‐κB pathway was recently identified as a novel positive regulator of muscle OXPHEN. METHODS We investigated markers and key regulators of muscle OXPHEN, including the alternative NF‐κB pathway, in m. gastrocnemius of mice upon hind limb suspension/reloading (HLS/RL). RESULTS Expression levels of oxidative phosphorylation (OXPHOS) sub‐units and oxidative myosin heavy chain (MyHC) isoforms I and IIa decreased after HLS and increased rapidly upon RL. Expression levels of PGC‐1α and PGC‐1β as well as mitochondrial transcription factor A (Tfam) showed a similar response to HLS/RL. Although peroxisome proliferator‐activated receptor γ (PPAR‐γ), nuclear respiratory factor 1 (NRF‐1) and sirtuin 1 (SIRT‐1) levels remained unaltered upon HLS, they were potently induced during the RL phase. Moreover, upon RL, levels of IKK‐α increased and phosphorylation and subsequent processing of P100 to P52 was elevated indicative of alternative NF‐κB activation. CONCLUSION RL‐induced recovery of muscle OXPHEN is associated with potent activation of the alternative NF‐κB pathway. This study was sponsored by the Netherlands Asthma Foundation (NAF 3.2.09.068 )