Activation of alternative NF-κB signaling during recovery of disuse-induced loss of muscle oxidative phenotype.

A.H. Remels*, N.A.M. Pansters, H.R. Gosker, A.M. Schols, R.C. Langen

*Corresponding author for this work

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Abstract

BACKGROUND: Physical inactivity-induced loss of skeletal muscle phenotype (OXPHEN), often observed in chronic disease, adversely affects functioning and quality of life. Potential therapeutic targets remain to identified as the molecular mechanisms involved in reloading-induced muscle OXPHEN remain incompletely understood. We hypothesized a role for alternative NF-kappaB, as a recently identified positive regulator of OXPHEN, in reloading-induced alterations in muscle OXPHEN. METHODS: regulators (including alternative NF-kappaB signaling) of muscle OXPHEN investigated in gastrocnemius muscle of mice subjected to a hind limb suspension/reloading (HLS/RL) protocol. RESULTS: Expression levels of phosphorylation (OXPHOS) sub-units and slow myosin heavy chain (MyHC) and IIA increased rapidly upon RL. After an initial decrease upon HLS, levels of peroxisome proliferator-activated receptor (PPAR) gamma co- (PGC) molecules PGC-1alpha and PGC-1beta and mRNA levels of transcription factor A (Tfam) and estrogen-related receptor alpha (ERR- increased upon RL. PPAR-delta, nuclear respiratory factor 1 (NRF-1), and sirtuin 1 mRNA levels increased during RL although expression levels unaltered upon HLS. In addition, both Tfam and NRF-1 protein levels significantly during the RL period. Moreover, upon RL, IKK-alpha mRNA levels increased and phosphorylation of P100 and subsequent processing elevated, reflecting alternative NF-kappaB activation. CONCLUSION: RL- recovery of muscle OXPHEN is associated with activation of alternative
Original languageEnglish
Pages (from-to)E615-E626
Number of pages12
JournalAmerican Journal of Physiology : Endocrinology and Metabolism
Volume306
Issue number6
DOIs
Publication statusPublished - Mar 2014

Keywords

  • reloading
  • skeletal muscle
  • alternative nuclear factor-kappa B
  • peroxisome proliferator-activated receptor-gamma coactivator
  • SKELETAL-MUSCLE
  • MITOCHONDRIAL BIOGENESIS
  • SOLEUS MUSCLE
  • TIBIALIS ANTERIOR
  • GENE-EXPRESSION
  • ERR-ALPHA
  • DIFFERENTIATION
  • ADAPTATIONS
  • EXERCISE
  • ATROPHY

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