Acute exercise activates nuclear factor (NF)-κB signaling pathway in rat skeletal muscle

L. L. Ji, M. C. Gomez-Cabrera, N. Steinhafel, J. Vina

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229 Scopus citations


Two studies were performed to investigate the effects of an acute bout of physical exercise on the nuclear protein κB (NF-κB) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n=6) was run on the treadmill at 25 m/min, 5% grade, for 1 h or until exhaustion (Ex), and compared with a second group (n=6) injected with two doses of pyrrolidine dithiocarbamate (PDTC, 100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional groups of rats (n=6) were injected with either 8 mg/kg (i.p.) of lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline (C) and killed at resting condition. Ex rats showed higher levels of NF-κB binding and P50 protein content in muscle nuclear extracts compared with C rats. Cytosolic IκBα and IκB kinase (IKK) contents were decreased, whereas phospho-IκBα and phospho-IKK contents were increased, comparing Ex vs. C. The exercise-induced activation of NF-κB signaling cascade was partially abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and exaggerated the effects observed in Ex rats. In Study 2, the time course of exercise-induced NF-κB activation was examined. Highest levels of NF-κB binding were observed at 2 h postexercise. Decreased cytosolic IκBα and increased phosphor-IκBα content were found 0-1 h postexercise whereas P65 reached peak levels at 2-4 h. These data suggest that the NF-κB signaling pathway can be activated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant production. The cascade of intracellular events may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier.

Original languageEnglish (US)
Pages (from-to)1499-1506
Number of pages8
JournalFASEB Journal
Issue number13
StatePublished - Oct 1 2004


  • Nuclear protein κB
  • ROS
  • Redox signaling


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